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1

Exercise-induced mitochondrial biogenesis begins before the increase in muscle PGC-1alpha expression.  

PubMed

Exercise results in rapid increases in expression of the transcription coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and in mitochondrial biogenesis in skeletal muscle. PGC-1alpha regulates and coordinates mitochondrial biogenesis, and overexpression of PGC-1alpha in muscle cells results in increases in mitochondrial content. In this context, it has been proposed that the increase in PGC-1alpha protein expression mediates the exercise-induced increase in mitochondrial biogenesis. However, we found that mitochondrial proteins with a short half-life increase as rapidly as, or more rapidly than, PGC-1alpha protein. This finding led us to hypothesize that activation, rather than increased expression, of PGC-1alpha mediates the initial phase of the exercise-induced increase in mitochondria. In this study, we found that most of the PGC-1alpha in resting skeletal muscle is in the cytosol. Exercise resulted in activation of p38 MAPK and movement of PGC-1alpha into the nucleus. In support of our hypothesis, binding of the transcription factor nuclear respiratory factor 1 (NRF-1) to the cytochrome c promoter and NRF-2 to the cytochrome oxidase subunit 4 promoter increased in response to exercise prior to an increase in PGC-1alpha protein. Furthermore, exercise-induced increases in the mRNAs of cytochrome c, delta-aminolevulinate synthase, and citrate synthase also occurred before an increase in PGC-1 protein. Thus, it appears that activation of PGC-1alpha may mediate the initial phase of the exercise-induced adaptive increase in muscle mitochondria, whereas the subsequent increase in PGC-1alpha protein sustains and enhances the increase in mitochondrial biogenesis. PMID:17099248

Wright, David C; Han, Dong-Ho; Garcia-Roves, Pablo M; Geiger, Paige C; Jones, Terry E; Holloszy, John O

2006-11-12

2

Regulation of exercise-induced fiber type transformation, mitochondrial biogenesis, and angiogenesis in skeletal muscle  

PubMed Central

Skeletal muscle exhibits superb plasticity in response to changes in functional demands. Chronic increases of skeletal muscle contractile activity, such as endurance exercise, lead to a variety of physiological and biochemical adaptations in skeletal muscle, including mitochondrial biogenesis, angiogenesis, and fiber type transformation. These adaptive changes are the basis for the improvement of physical performance and other health benefits. This review focuses on recent findings in genetically engineered animal models designed to elucidate the mechanisms and functions of various signal transduction pathways and gene expression programs in exercise-induced skeletal muscle adaptations.

Okutsu, Mitsuharu; Akhtar, Yasir N.; Lira, Vitor A.

2011-01-01

3

Mitochondrial biogenesis and healthy aging.  

PubMed

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha). Activators of PGC-1alpha include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1alpha. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1alpha such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process. PMID:18662766

López-Lluch, Guillermo; Irusta, Pablo M; Navas, Placido; de Cabo, Rafael

2008-07-09

4

MITOCHONDRIAL BIOGENESIS AND HEALTHY AGING  

PubMed Central

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of mitochondrial biogenesis and turnover, therefore, becomes critical for the maintenance of energy production, the prevention of endogenous oxidative stress and the promotion of healthy aging. Multiple endogenous and exogenous factors regulate mitochondrial biogenesis through the peroxisome proliferator-activated receptor gamma coactivator-1? (PGC-1?). Activators of PGC-1? include nitric oxide, CREB and AMPK. Calorie restriction (CR) and resveratrol, a proposed CR mimetic, also increase mitochondrial biogenesis through activation of PGC-1?. Moderate exercise also mimics CR by inducing mitochondrial biogenesis. Negative regulators of PGC-1? such as RIP140 and 160MBP suppress mitochondrial biogenesis. Another mechanism involved in mitochondrial maintenance is mitochondrial fission/fusion and this process also involves an increasing number of regulatory proteins. Dysfunction of either biogenesis or fission/fusion of mitochondria is associated with diseases of the neuromuscular system and aging, and a greater understanding of the regulation of these processes should help us to ultimately control the aging process.

Lopez-Lluch, Guillermo; Irusta, Pablo M.; Navas, Placido; de Cabo, Rafael

2008-01-01

5

Transcriptional integration of mitochondrial biogenesis  

PubMed Central

Gene regulatory factors encoded by the nuclear genome are essential for mitochondrial biogenesis and function. Some of these factors act exclusively within the mitochondria to regulate the control of mitochondrial transcription, translation and other functions. Others govern the expression of nuclear genes required for mitochondrial metabolism and organelle biogenesis. The peroxisome proliferator-activated receptor gamma coactivator-1 (PGC-1) family of transcriptional coactivators plays a major role in transducing and integrating physiological signals governing metabolism, differentiation and cell growth to the transcriptional machinery controlling mitochondrial functional capacity. Thus, the PGC-1 coactivators serve as a central component of the transcriptional regulatory circuitry that coordinately controls the energy-generating functions of mitochondria in accordance with the metabolic demands imposed by changing physiological conditions, senescence, and disease.

Scarpulla, Richard C.; Vega, Rick B.; Kelly, Daniel P.

2012-01-01

6

Interactions between bioenergetics and mitochondrial biogenesis  

Microsoft Academic Search

We studied the interaction between energy metabolism and mitochondrial biogenesis during myogenesis in C2C12 myoblasts. Metabolic rate was nearly constant throughout differentiation, although there was a shift in the relative importance of glycolytic and oxidative metabolism, accompanied by increases in pyruvate dehydrogenase activation state and total activity. These changes in mitochondrial bioenergetic parameters observed during differentiation occurred in the absence

Scot C. Leary; Brendan J. Battersby; Richard G. Hansford; Christopher D. Moyes

1998-01-01

7

Mitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised rats.  

PubMed

The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-?-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100. Examination of running distances over the 4-week period revealed that EN rats ran significantly longer throughout the entire duration of the exhaustive exercise period compared with the EC rats. Nutrient supplementation significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase, reversed increases in malondialdehyde, inhibited decreases in glutathione S-transferase and total antioxidant capacity in plasma, and suppressed the elevation of reactive oxygen species and apoptosis in splenic lymphocytes. Nutrient supplementation increased the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle. These findings suggest that mitochondrial nutrient supplementation can reduce exhaustive exercise-induced oxidative damage and mitochondrial dysfunction, thus leading to enhancement of physical performance and of fatigue recovery. PMID:21507065

Sun, M; Qian, F; Shen, W; Tian, C; Hao, J; Sun, L; Liu, J

2011-04-21

8

Mitochondrial biogenesis and function in Arabidopsis.  

PubMed

Mitochondria represent the powerhouse of cells through their synthesis of ATP. However, understanding the role of mitochondria in the growth and development of plants will rely on a much deeper appreciation of the complexity of this organelle. Arabidopsis research has provided clear identification of mitochondrial components, allowed wide-scale analysis of gene expression, and has aided reverse genetic manipulation to test the impact of mitochondrial component loss on plant function. Forward genetics in Arabidopsis has identified mitochondrial involvement in mutations with notable impacts on plant metabolism, growth and development. Here we consider the evidence for components involved in mitochondria biogenesis, metabolism and signalling to the nucleus. PMID:22303236

Millar, A Harvey; Small, Ian D; Day, David A; Whelan, James

2008-07-09

9

Mitochondrial Biogenesis and Function in Arabidopsis†  

PubMed Central

Mitochondria represent the powerhouse of cells through their synthesis of ATP. However, understanding the role of mitochondria in the growth and development of plants will rely on a much deeper appreciation of the complexity of this organelle. Arabidopsis research has provided clear identification of mitochondrial components, allowed wide-scale analysis of gene expression, and has aided reverse genetic manipulation to test the impact of mitochondrial component loss on plant function. Forward genetics in Arabidopsis has identified mitochondrial involvement in mutations with notable impacts on plant metabolism, growth and development. Here we consider the evidence for components involved in mitochondria biogenesis, metabolism and signalling to the nucleus.

Millar, A. Harvey; Small, Ian D.; Day, David A.; Whelan, James

2008-01-01

10

Mitochondrial Biogenesis in Mammals: The Role of Endogenous Nitric Oxide  

Microsoft Academic Search

Nitric oxide was found to trigger mitochondrial biogenesis in cells as diverse as brown adipocytes and 3T3-L1, U937, and HeLa cells. This effect of nitric oxide was dependent on guanosine 3',5'-monophosphate (cGMP) and was mediated by the induction of peroxisome proliferator-activated receptor gamma coactivator 1alpha, a master regulator of mitochondrial biogenesis. Moreover, the mitochondrial biogenesis induced by exposure to cold

Enzo Nisoli; Emilio Clementi; Clara Paolucci; Valeria Cozzi; Cristina Tonello; Clara Sciorati; Renata Bracale; Alessandra Valerio; Maura Francolini; Salvador Moncada; Michele O. Carruba

2003-01-01

11

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis  

Microsoft Academic Search

Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an

David C. Hess; Chad L. Myers; Curtis Huttenhower; Matthew A. Hibbs; Alicia P. Hayes; Jadine Paw; John J. Clore; Rosa M. Mendoza; Bryan San Luis; Corey Nislow; Guri Giaever; Michael Costanzo; Olga G. Troyanskaya; Amy A. Caudy

2009-01-01

12

Coordination of Nuclear and Mitochondrial Genome Expression during Mitochondrial Biogenesis in Arabidopsis  

Microsoft Academic Search

Mitochondrial biogenesis and function require the regulated and coordinated expression of nuclear and mitochondrial genomes throughout plant development and in response to cellular and environmental signals. To investigate the levels at which the expression of nuclear and mitochondrially encoded proteins is coordinated, we established an Arabidopsis thaliana cell culture system to modulate mitochondrial biogenesis in response to sugar starvation and

Philippe Giege; Lee J. Sweetlove; Valerie Cognat; Christopher J. Leaverb

2005-01-01

13

Mitochondrial biogenesis in the axons of vertebrate peripheral neurons  

Microsoft Academic Search

Mitochondria are widely distributed via regulated transport in neurons, but their sites of biogenesis remain uncertain. Most mitochondrial proteins are encoded in the nuclear genome, and evidence has suggested that mitochondrial DNA (mtDNA) replication occurs mainly or entirely in the cell body. However, it has also become clear that nuclear-encoded mitochondrial proteins can be translated in the axon, and that

Mandana Amiri; Peter J. Hollenbeck

2008-01-01

14

Nuclear activators and coactivators in mammalian mitochondrial biogenesis  

Microsoft Academic Search

The biogenesis of mitochondria requires the expression of a large number of genes, most of which reside in the nuclear genome. The protein-coding capacity of mtDNA is limited to 13 respiratory subunits necessitating that nuclear regulatory factors play an important role in governing nucleo-mitochondrial interactions. Two classes of nuclear transcriptional regulators implicated in mitochondrial biogenesis have emerged in recent years.

Richard C Scarpulla

2002-01-01

15

A high throughput respirometric assay for mitochondrial biogenesis and toxicity  

PubMed Central

Mitochondria are a common target of toxicity for drugs and other chemicals, and results in decreased aerobic metabolism and cell death. In contrast, mitochondrial biogenesis restores cell vitality and there is a need for new agents to induce biogenesis. Current cell-based models of mitochondrial biogenesis or toxicity are inadequate because cultured cell lines are highly glycolytic with minimal aerobic metabolism and altered mitochondrial physiology. In addition, there are no high-throughput, real-time assays that assess mitochondrial function. We adapted primary cultures of renal proximal tubular cells (RPTC) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions and used the Seahorse Biosciences analyzer to measure mitochondrial function in real time in multi-well plates. Using uncoupled respiration as a marker of electron transport chain (ETC) integrity, the nephrotoxicants cisplatin, HgCl2 and gentamicin exhibited mitochondrial toxicity prior to decreases in basal respiration and cell death. Conversely, using FCCP-uncoupled respiration as a marker of maximal ETC activity, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), SRT1720, resveratrol, daidzein, and metformin produced mitochondrial biogenesis in RPTC. The merger of the RPTC model and multi-well respirometry results in a single high throughput assay to measure mitochondrial biogenesis and toxicity, and nephrotoxic potential.

Beeson, Craig C.; Beeson, Gyda C.; Schnellmann, Rick G.

2010-01-01

16

Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis  

SciTech Connect

Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes.

Palmeira, Carlos M. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal)], E-mail: palmeira@ci.uc.pt; Rolo, Anabela P. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal); Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B. [Department of Biochemistry and Molecular Biology, University of Minnesota School of Medicine, Duluth, MN (United States)

2007-12-01

17

Molecular Genetics of Mitochondrial Biogenesis in Maize.  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mitochondrial genome encodes proteins essential for mitochondrial respiration and ATP synthesis. Nuclear gene products, however, are required for the expression of mitochondrial genes and the elaboration of functional mitochondrial protein complexes. We are exploiting a unique collection of maiz...

18

Sirtuin 1 (SIRT1) Deacetylase Activity Is Not Required for Mitochondrial Biogenesis or Peroxisome Proliferator-activated Receptor-? Coactivator-1? (PGC-1?) Deacetylation following Endurance Exercise*  

PubMed Central

The protein deacetylase, sirtuin 1 (SIRT1), is a proposed master regulator of exercise-induced mitochondrial biogenesis in skeletal muscle, primarily via its ability to deacetylate and activate peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?). To investigate regulation of mitochondrial biogenesis by SIRT1 in vivo, we generated mice lacking SIRT1 deacetylase activity in skeletal muscle (mKO). We hypothesized that deacetylation of PGC-1? and mitochondrial biogenesis in sedentary mice and after endurance exercise would be impaired in mKO mice. Skeletal muscle contractile characteristics were determined in extensor digitorum longus muscle ex vivo. Mitochondrial biogenesis was assessed after 20 days of voluntary wheel running by measuring electron transport chain protein content, enzyme activity, and mitochondrial DNA expression. PGC-1? expression, nuclear localization, acetylation, and interacting protein association were determined following an acute bout of treadmill exercise (AEX) using co-immunoprecipitation and immunoblotting. Contrary to our hypothesis, skeletal muscle endurance, electron transport chain activity, and voluntary wheel running-induced mitochondrial biogenesis were not impaired in mKO versus wild-type (WT) mice. Moreover, PGC-1? expression, nuclear translocation, activity, and deacetylation after AEX were similar in mKO versus WT mice. Alternatively, we made the novel observation that deacetylation of PGC-1? after AEX occurs in parallel with reduced nuclear abundance of the acetyltransferase, general control of amino-acid synthesis 5 (GCN5), as well as reduced association between GCN5 and nuclear PGC-1?. These findings demonstrate that SIRT1 deacetylase activity is not required for exercise-induced deacetylation of PGC-1? or mitochondrial biogenesis in skeletal muscle and suggest that changes in GCN5 acetyltransferase activity may be an important regulator of PGC-1? activity after exercise.

Philp, Andrew; Chen, Ai; Lan, Debin; Meyer, Gretchen A.; Murphy, Anne N.; Knapp, Amy E.; Olfert, I. Mark; McCurdy, Carrie E.; Marcotte, George R.; Hogan, Michael C.; Baar, Keith; Schenk, Simon

2011-01-01

19

Diabetes regulates mitochondrial biogenesis and fission in mouse neurons  

Microsoft Academic Search

Aims\\/hypothesis  Normal mitochondrial activity is a critical component of neuronal metabolism and function. Disruption of mitochondrial activity\\u000a by altered mitochondrial fission and fusion is the root cause of both neurodegenerative disorders and Charcot–Marie–Tooth\\u000a type 2A inherited neuropathy. This study addressed the role of mitochondrial fission in the pathogenesis of diabetic neuropathy.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Mitochondrial biogenesis and fission were assayed in both in vivo

J. L. Edwards; A. Quattrini; S. I. Lentz; C. Figueroa-Romero; F. Cerri; C. Backus; Y. Hong; E. L. Feldman

2010-01-01

20

Mitochondrial biogenesis and the development of diabetic retinopathy.  

PubMed

Retinal mitochondria become dysfunctional and their DNA (mtDNA) is damaged in diabetes. The biogenesis of mitochondrial DNA is tightly controlled by nuclear-mitochondrial transcriptional factors, and translocation of transcription factor A (TFAM) to the mitochondria is essential for transcription and replication. Our aim is to investigate the effects of diabetes on nuclear-mitochondrial communication in the retina and its role in the development of retinopathy. Damage of mtDNA, copy number, and biogenesis (PGC1, NRF1, TFAM) were analyzed in the retinas from streptozotocin-diabetic wild-type (WT) and MnSOD transgenic (Tg) mice. Binding between TFAM and chaperone Hsp70 was quantified by coimmunoprecipitation. The key parameters were confirmed in isolated retinal endothelial cells and in the retinas from human donors with diabetic retinopathy. Diabetes in WT mice increased retinal mtDNA damage and decreased copy number. The gene transcripts of PGC1, NRF1, and TFAM were increased, but mitochondrial accumulation of TFAM was significantly decreased, and the binding of Hsp70 and TFAM was subnormal compared to WT nondiabetic mice. However, Tg diabetic mice were protected from retinal mtDNA damage and alterations in mitochondrial biogenesis. In retinal endothelial cells, high glucose decreased the number of mitochondria, as demonstrated by MitoTracker green staining and by electron microscopy, and impaired the transcriptional factors. Similar alterations in biogenesis were observed in the donors with diabetic retinopathy. Thus, retinal mitochondrial biogenesis is under the control of superoxide radicals and is impaired in diabetes, possibly by decreased transport of TFAM to the mitochondria. Modulation of biogenesis by pharmaceutical or molecular means may provide a potential strategy to retard the development/progression of diabetic retinopathy. PMID:21911054

Santos, Julia M; Tewari, Shikha; Goldberg, Andrew F X; Kowluru, Renu A

2011-08-25

21

DHTKD1 is essential for mitochondrial biogenesis and function maintenance.  

PubMed

Maintaining the functional integrity of mitochondria is crucial for cell function, signal transduction and overall cell activities. Mitochondrial dysfunctions may alter energy metabolism and in many cases are associated with neurological diseases. Recent studies have reported that mutations in dehydrogenase E1 and transketolase domain-containing 1 (DHTKD1), a mitochondrial protein encoding gene, could cause neurological abnormalities. However, the function of DHTKD1 in mitochondria remains unknown. Here, we report a strong correlation of DHTKD1 expression level with ATP production, revealing the fact that DHTKD1 plays a critical role in energy production in mitochondria. Moreover, suppression of DHTKD1 leads to impaired mitochondrial biogenesis and increased reactive oxygen species (ROS), thus leading to retarded cell growth and increased cell apoptosis. These findings demonstrate that DHTKD1 contributes to mitochondrial biogenesis and function maintenance. PMID:24076469

Xu, Wangyang; Zhu, Houbao; Gu, Mingmin; Luo, Qingqiong; Ding, Jieying; Yao, Yuting; Chen, Fuxiang; Wang, Zhugang

2013-09-27

22

Exercise-induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling.  

PubMed

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-?-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-?-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise. PMID:23733522

Ziolkowski, Wieslaw; Vadhana Ms, Dhivya; Kaczor, Jan Jacek; Olek, Robert Antoni; Flis, Damian Jozef; Halon, Malgorzata; Wozniak, Michal; Fedeli, Donatella; Carloni, Manuel; Antosiewicz, Jedrzej; Gabbianelli, Rosita

2013-06-03

23

Coordination of Nuclear and Mitochondrial Genome Expression during Mitochondrial Biogenesis in ArabidopsisW?  

PubMed Central

Mitochondrial biogenesis and function require the regulated and coordinated expression of nuclear and mitochondrial genomes throughout plant development and in response to cellular and environmental signals. To investigate the levels at which the expression of nuclear and mitochondrially encoded proteins is coordinated, we established an Arabidopsis thaliana cell culture system to modulate mitochondrial biogenesis in response to sugar starvation and refeeding. Sucrose deprivation led to structural changes in mitochondria, a decrease in mitochondrial volume, and a reduction in the rate of cellular respiration. All these changes could be reversed by the readdition of sucrose. Analysis of the relative mRNA transcript abundance of genes encoding nuclear and mitochondrially encoded proteins revealed that there was no coordination of expression of the two genomes at the transcript level. An analysis of changes in abundance and assembly of nuclear-encoded and mitochondrially encoded subunits of complexes I to V of the mitochondrial inner membrane in organello protein synthesis and competence for protein import by isolated mitochondria suggested that coordination occurs at the level of protein-complex assembly. These results further suggest that expression of the mitochondrial genome is insensitive to the stress imposed by sugar starvation and that mitochondrial biogenesis is regulated by changes in nuclear gene expression and coordinated at the posttranslational level.

Giege, Philippe; Sweetlove, Lee J.; Cognat, Valerie; Leaver, Christopher J.

2005-01-01

24

Computationally Driven, Quantitative Experiments Discover Genes Required for Mitochondrial Biogenesis  

PubMed Central

Mitochondria are central to many cellular processes including respiration, ion homeostasis, and apoptosis. Using computational predictions combined with traditional quantitative experiments, we have identified 100 proteins whose deficiency alters mitochondrial biogenesis and inheritance in Saccharomyces cerevisiae. In addition, we used computational predictions to perform targeted double-mutant analysis detecting another nine genes with synthetic defects in mitochondrial biogenesis. This represents an increase of about 25% over previously known participants. Nearly half of these newly characterized proteins are conserved in mammals, including several orthologs known to be involved in human disease. Mutations in many of these genes demonstrate statistically significant mitochondrial transmission phenotypes more subtle than could be detected by traditional genetic screens or high-throughput techniques, and 47 have not been previously localized to mitochondria. We further characterized a subset of these genes using growth profiling and dual immunofluorescence, which identified genes specifically required for aerobic respiration and an uncharacterized cytoplasmic protein required for normal mitochondrial motility. Our results demonstrate that by leveraging computational analysis to direct quantitative experimental assays, we have characterized mutants with subtle mitochondrial defects whose phenotypes were undetected by high-throughput methods.

Hess, David C.; Hayes, Alicia P.; Paw, Jadine; Clore, John J.; Mendoza, Rosa M.; Luis, Bryan San; Nislow, Corey; Giaever, Guri; Costanzo, Michael; Troyanskaya, Olga G.; Caudy, Amy A.

2009-01-01

25

Mitochondrial Biogenesis in the Axons of Vertebrate Peripheral Neurons  

PubMed Central

Mitochondria are widely distributed via regulated transport in neurons, but their sites of biogenesis remain uncertain. Most mitochondrial proteins are encoded in the nuclear genome, and evidence has suggested that mitochondrial DNA (mtDNA) replication occurs mainly or entirely in the cell body. However, it has also become clear that nuclear-encoded mitochondrial proteins can be translated in the axon and that components of the mitochondrial replication machinery reside there as well. We assessed directly whether mtDNA replication can occur in the axons of chick peripheral neurons labeled with 5-bromo-2?-deoxyuridine (BrdU). In axons that were physically separated from the cell body or had disrupted organelle transport between the cell bodies and axons, a significant fraction of mtDNA synthesis continued. We also detected the mitochondrial fission protein Drp1 in neurons by immunofluorescence or expression of GFP-Drp1. Its presence and distribution on the majority of axonal mitochondria indicated that a substantial number had undergone recent division in the axon. Because the morphology of mitochondria is maintained by the balance of fission and fusion events, we either inhibited Drp1 expression by RNAi or overexpressed the fusion protein Mfn1. Both methods resulted in significantly longer mitochondria in axons, including many at a great distance from the cell body. These data indicate that mitochondria can replicate their DNA, divide, and fuse locally within the axon; thus, the biogenesis of mitochondria is not limited to the cell body.

Amiri, Mandana; Hollenbeck, Peter J.

2008-01-01

26

Upregulation of human selenoprotein H in murine hippocampal neuronal cells promotes mitochondrial biogenesis and functional performance.  

PubMed

Overexpression of selenoprotein H (SelH) gene provides neuroprotection in neurons against UVB-induced cell death by blocking the mitochondrial-initiated apoptotic cell death pathway. This study examined the effects of SelH on mitochondrial biogenesis and mitochondrial function. The results demonstrated that overexpression of SelH gene in neuronal HT22 cells significantly increased the levels of mitochondrial biogenesis regulators, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor-? coactivator-1 alpha (PGC-1?) and mitochondrial transcription factor A (Tfam). Mitochondrial cytochrome c content was elevated, mass was increased and respiration was enhanced. SelH transfection ameliorated ultra violet B (UVB)-induced suppression of mitochondrial biogenesis markers and depolarization of mitochondrial membrane potential. Overexpression of SelH promotes mitochondrial biogenesis and improves mitochondrial functional performance. PMID:20656065

Mendelev, Natalia; Mehta, Suresh L; Witherspoon, Sam; He, Qingping; Sexton, Jonathan Z; Li, P Andy

2010-07-23

27

Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia  

PubMed Central

Background Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. Results The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24?h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2?mg/kg?i.p. once a day for 7?days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-? coactivator 1alpha (PGC-1?) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy. Conclusions These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis.

2012-01-01

28

Mild Mitochondrial Uncoupling and Calorie Restriction Increase Fasting eNOS, Akt and Mitochondrial Biogenesis  

PubMed Central

Enhanced mitochondrial biogenesis promoted by eNOS activation is believed to play a central role in the beneficial effects of calorie restriction (CR). Since treatment of mice with dinitrophenol (DNP) promotes health and lifespan benefits similar to those observed in CR, we hypothesized that it could also impact biogenesis. We found that DNP and CR increase citrate synthase activity, PGC-1?, cytochrome c oxidase and mitofusin-2 expression, as well as fasting plasma levels of NO• products. In addition, eNOS and Akt phosphorylation in skeletal muscle and visceral adipose tissue was activated in fasting CR and DNP animals. Overall, our results indicate that systemic mild uncoupling activates eNOS and Akt-dependent pathways leading to mitochondrial biogenesis.

Cerqueira, Fernanda M.; Laurindo, Francisco R. M.; Kowaltowski, Alicia J.

2011-01-01

29

Role of MINOS in mitochondrial membrane architecture and biogenesis.  

PubMed

Mitochondria possess a complex architecture with two membranes. The inner membrane is divided into two domains: the inner boundary membrane, which is adjacent to the outer membrane, and membrane invaginations termed cristae. Both domains are connected by tubular openings, the crista junctions. Recent studies led to the identification of a large protein complex that is crucial for establishing inner-membrane architecture. This mitochondrial inner-membrane organizing system (MINOS) interacts with protein translocases of the outer membrane that are functionally connected to the endoplasmic reticulum (ER)-mitochondria encounter structure. Here, we propose that MINOS forms a central part of an ER-mitochondria organizing network (ERMIONE) that controls mitochondrial membrane architecture and biogenesis. PMID:22386790

van der Laan, Martin; Bohnert, Maria; Wiedemann, Nils; Pfanner, Nikolaus

2012-03-02

30

Regulation of Mitochondrial Biogenesis in Skeletal Muscle by CaMK  

Microsoft Academic Search

Endurance exercise training promotes mitochondrial biogenesis in skeletal muscle and enhances muscle oxidative capacity, but the signaling mechanisms involved are poorly understood. To investigate this adaptive process, we generated transgenic mice that selectively express in skeletal muscle a constitutively active form of calcium\\/calmodulin-dependent protein kinase IV (CaMKIV*). Skeletal muscles from these mice showed augmented mitochondrial DNA replication and mitochondrial biogenesis,

Hai Wu; Shane B. Kanatous; Frederick A. Thurmond; Teresa Gallardo; Eiji Isotani; Rhonda Bassel-Duby; R. Sanders Williams

2002-01-01

31

The ?2-adrenoceptor agonist formoterol stimulates mitochondrial biogenesis.  

PubMed

Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the ?-adrenoceptor (?-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple ?-AR agonists: isoproterenol (nonselective ?-AR agonist), (±)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective ?(3)-AR agonist), and formoterol (selective ?(2)-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the ?-AR antagonist propranolol and the ?(2)-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor ? coactivator 1?, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1? subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet that increased mitochondrial respiratory capacity. These data provide compelling evidence for the use and development of ?(2)-AR ligands for therapeutic MB. PMID:22490378

Wills, Lauren P; Trager, Richard E; Beeson, Gyda C; Lindsey, Christopher C; Peterson, Yuri K; Beeson, Craig C; Schnellmann, Rick G

2012-04-06

32

Erythropoietin Activates Mitochondrial Biogenesis and Couples Red Cell Mass to Mitochondrial Mass in the Heart  

PubMed Central

Rationale Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia. Objective We examined the hypothesis that EPO receptor (EpoR) ligand-binding, which activates endothelial nitric oxide synthase (eNOS), regulates the pro-survival program of mitochondrial biogenesis in the heart. Methods and Results We investigated the effects of EPO on mitochondrial biogenesis over 14 days in healthy mice. Mice expressing a mitochondrial GFP-reporter construct demonstrated sharp increases in myocardial mitochondrial density post-EPO by 3 days that peaked at 7 days and surpassed hepatic or renal effects and anteceded significant increases in blood hemoglobin content. Quantitatively, in wild-type (Wt) mice, Complex II activity, State 3 respiration and mtDNA copy number increased significantly; also resting energy expenditure and natural running speed improved with no evidence of an increase in LV mass index. Mechanistically, EPO activated cardiac mitochondrial biogenesis by enhancement of nuclear respiratory factor-1 (NRF-1), PGC-1? and mitochondrial transcription factor-A gene expression in Wt, but not in eNOS-/- or Akt1-/- mice. EpoR was required, as EpoR silencing in cardiomyocytes blocked EPO-mediated nuclear translocation of NRF-1. Conclusions These findings support a new physiological and protective role for EPO, acting through its cell surface receptor and eNOS-Akt1 signal transduction, in matching cardiac mitochondrial mass to the convective O2 transport capacity as erythrocyte mass expands.

Carraway, Martha S.; Suliman, Hagir B.; Jones, W. Schuyler; Chen, Chien-Wen; Babiker, Abdelwahid; Piantadosi, Claude A

2010-01-01

33

The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy  

PubMed Central

The clinical utility of anthracycline anticancer agents, especially doxorubicin, is limited by a progressive toxic cardiomyopathy linked to mitochondrial damage and cardiomyocyte apoptosis. Here we demonstrate that the post-doxorubicin mouse heart fails to upregulate the nuclear program for mitochondrial biogenesis and its associated intrinsic antiapoptosis proteins, leading to severe mitochondrial DNA (mtDNA) depletion, sarcomere destruction, apoptosis, necrosis, and excessive wall stress and fibrosis. Furthermore, we exploited recent evidence that mitochondrial biogenesis is regulated by the CO/heme oxygenase (CO/HO) system to ameliorate doxorubicin cardiomyopathy in mice. We found that the myocardial pathology was averted by periodic CO inhalation, which restored mitochondrial biogenesis and circumvented intrinsic apoptosis through caspase-3 and apoptosis-inducing factor. Moreover, CO simultaneously reversed doxorubicin-induced loss of DNA binding by GATA-4 and restored critical sarcomeric proteins. In isolated rat cardiac cells, HO-1 enzyme overexpression prevented doxorubicin-induced mtDNA depletion and apoptosis via activation of Akt1/PKB and guanylate cyclase, while HO-1 gene silencing exacerbated doxorubicin-induced mtDNA depletion and apoptosis. Thus doxorubicin disrupts cardiac mitochondrial biogenesis, which promotes intrinsic apoptosis, while CO/HO promotes mitochondrial biogenesis and opposes apoptosis, forestalling fibrosis and cardiomyopathy. These findings imply that the therapeutic index of anthracycline cancer chemotherapeutics can be improved by the protection of cardiac mitochondrial biogenesis.

Suliman, Hagir B.; Carraway, Martha Sue; Ali, Abdelwahid S.; Reynolds, Chrystal M.; Welty-Wolf, Karen E.; Piantadosi, Claude A.

2007-01-01

34

AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation  

Microsoft Academic Search

Mitochondrial biogenesis is a critical adaptation to chronic energy deprivation, yet the signaling mechanisms responsible for this response are poorly understood. To examine the role of AMP-activated protein kinase (AMPK), an evolutionarily conserved fuel sensor, in mitochondrial biogenesis we studied transgenic mice expressing a dominant-negative mutant of AMPK in muscle (DN-AMPK). Both DN-AMPK and WT mice were treated with -guanidinopropionic

Haihong Zong; Jian Ming Ren; Lawrence H. Young; Marc Pypaert; James Mu; Morris J. Birnbaum; Gerald I. Shulman

2002-01-01

35

Role of mitochondrial inner membrane organizing system in protein biogenesis of the mitochondrial outer membrane.  

PubMed

Mitochondria contain two membranes, the outer membrane and the inner membrane with folded cristae. The mitochondrial inner membrane organizing system (MINOS) is a large protein complex required for maintaining inner membrane architecture. MINOS interacts with both preprotein transport machineries of the outer membrane, the translocase of the outer membrane (TOM) and the sorting and assembly machinery (SAM). It is unknown, however, whether MINOS plays a role in the biogenesis of outer membrane proteins. We have dissected the interaction of MINOS with TOM and SAM and report that MINOS binds to both translocases independently. MINOS binds to the SAM complex via the conserved polypeptide transport-associated domain of Sam50. Mitochondria lacking mitofilin, the large core subunit of MINOS, are impaired in the biogenesis of ?-barrel proteins of the outer membrane, whereas mutant mitochondria lacking any of the other five MINOS subunits import ?-barrel proteins in a manner similar to wild-type mitochondria. We show that mitofilin is required at an early stage of ?-barrel biogenesis that includes the initial translocation through the TOM complex. We conclude that MINOS interacts with TOM and SAM independently and that the core subunit mitofilin is involved in biogenesis of outer membrane ?-barrel proteins. PMID:22918945

Bohnert, Maria; Wenz, Lena-Sophie; Zerbes, Ralf M; Horvath, Susanne E; Stroud, David A; von der Malsburg, Karina; Müller, Judith M; Oeljeklaus, Silke; Perschil, Inge; Warscheid, Bettina; Chacinska, Agnieszka; Veenhuis, Marten; van der Klei, Ida J; Daum, Günther; Wiedemann, Nils; Becker, Thomas; Pfanner, Nikolaus; van der Laan, Martin

2012-08-23

36

Skeletal muscle and beyond: the role of exercise as a mediator of systemic mitochondrial biogenesis.  

PubMed

It has been known for more than 4 decades that exercise causes increases in skeletal muscle mitochondrial enzyme content and activity (i.e., mitochondrial biogenesis). Increasing evidence now suggests that exercise can induce mitochondrial biogenesis in a wide range of tissues not normally associated with the metabolic demands of exercise. Perturbations in mitochondrial content and (or) function have been linked to a wide variety of diseases, in multiple tissues, and exercise may serve as a potent approach by which to prevent and (or) treat these pathologies. In this context, the purpose of this review is to highlight the effects of exercise, and the underlying mechanisms therein, on the induction of mitochondrial biogenesis in skeletal muscle, adipose tissue, liver, brain, and kidney. PMID:21888528

Little, Jonathan P; Safdar, Adeel; Benton, Carley R; Wright, David C

2011-09-02

37

Resveratrol protects cardiomyocytes from oxidative stress through SIRT1 and mitochondrial biogenesis signaling pathways.  

PubMed

Reactive oxygen species (ROS) is generated by oxidative stress and plays an important role in various cardiac pathologies. The SIRT1 signaling pathway and mitochondrial biogenesis play essential roles in mediating the production of ROS. SIRT1 activated by resveratrol protects cardiomyocytes from oxidative stress, but the exact mechanisms by which SIRT1 prevents oxidative stress, and its relationship with mitochondrial biogenesis, remain unclear. In this study, it was observed that after stimulation with 50?MH2O2 for 6h, H9C2 cells produced excessive ROS and downregulated SIRT1. The mitochondrial protein NDUFA13 was also downregulated by ROS mediated by SIRT1. Resveratrol induced the expression of SIRT1 and mitochondrial genes NDUFA1, NDUFA2, NDUFA13 and Mn-SOD. However, the production of these genes was reversed by SIRT1 inhibitor nicotinamide. These results suggest that resveratrol inhibits ROS generation in cardiomyocytes via SIRT1 and mitochondrial biogenesis signaling pathways. PMID:23891692

Li, Yong-guang; Zhu, Wei; Tao, Jian-ping; Xin, Ping; Liu, Ming-ya; Li, Jing-bo; Wei, Meng

2013-07-24

38

Heat exposure does not alter eccentric exercise-induced increases in mitochondrial calcium and respiratory dysfunction  

Microsoft Academic Search

Eccentric exercise can lead to muscle damage including dramatic changes to mitochondrial calcium content (MCC) and impaired\\u000a respiratory function. Heat acclimation can create a cross-tolerance to a number of stresses including eccentric exercise but\\u000a little is known about any protection to mitochondria. We hypothesised that intermittent heat exposure will lead to improved\\u000a control of MCC and to preserved mitochondrial function

Ben Rattray; C. Caillaud; P. A. Ruell; M. W. Thompson

39

Building the Powerhouse: What are the Signals Involved in Plant Mitochondrial Biogenesis?  

PubMed

With a central role in respiration and ATP production, regulation of mitochondrial form and function is essential for cell and organism survival. Our understanding of the molecular mechanisms and signaling events underlying plant mitochondrial biogenesis is limited. In a recent paper published in the Journal of Biological Chemistry we have demonstrated aspects of mitochondrial biogenesis that are dependent on an oxygen signal in the monocot model, rice. Specifically, we identified (1) a set of genes encoding mitochondrial components that are responsive to oxygen levels and (2) that a lack of oxygen represses the normal increase in the mitochondrial protein import capacity during germination, and that these changes culminate in a modified mitochondrial proteome and altered respiratory activity. These findings can be combined with an earlier study, which gave insights into the characteristics of promitochondrial structures found in dry seeds and how they change during the germination process. Together they provide evidence for regulation of mitochondrial biogenesis by developmental and environmental cues and transcriptional and post-transcriptional events. This information can be used to build a model of plant mitochondrial biogenesis within the context of seed germination and oxygen availability. PMID:19704623

Howell, Katharine A; Millar, A Harvey; Whelan, James

2007-09-01

40

Cannabinoid Receptor Stimulation Impairs Mitochondrial Biogenesis in Mouse White Adipose Tissue, Muscle, and Liver  

PubMed Central

OBJECTIVE Cannabinoid type 1 (CB1) receptor is involved in whole-body and cellular energy metabolism. We asked whether CB1 receptor stimulation was able to decrease mitochondrial biogenesis in different metabolically active tissues of obese high-fat diet (HFD)-fed mice. RESEARCH DESIGN AND METHODS The effects of selective CB1 agonist arachidonyl-2-chloroethanolamide (ACEA) and endocannabinoids anandamide and 2-arachidonoylglycerol on endothelial nitric oxide synthase (eNOS) expression were examined, as were mitochondrial DNA amount and mitochondrial biogenesis parameters in cultured mouse and human white adipocytes. These parameters were also investigated in white adipose tissue (WAT), muscle, and liver of mice chronically treated with ACEA. Moreover, p38 mitogen-activated protein kinase (MAPK) phosphorylation was investigated in WAT and isolated mature adipocytes from eNOS?/? and wild-type mice. eNOS, p38 MAPK, adenosine monophosphate–activated protein kinase (AMPK), and mitochondrial biogenesis were investigated in WAT, muscle, and liver of HFD mice chronically treated with ACEA. RESULTS ACEA decreased mitochondrial biogenesis and eNOS expression, activated p38 MAPK, and reduced AMPK phosphorylation in white adipocytes. The ACEA effects on mitochondria were antagonized by nitric oxide donors and by p38 MAPK silencing. White adipocytes from eNOS?/? mice displayed higher p38 MAPK phosphorylation than wild-type animals under basal conditions, and ACEA was ineffective in cells lacking eNOS. Moreover, mitochondrial biogenesis was downregulated, while p38 MAPK phosphorylation was increased and AMPK phosphorylation was decreased in WAT, muscle, and liver of ACEA-treated mice on a HFD. CONCLUSIONS CB1 receptor stimulation decreases mitochondrial biogenesis in white adipocytes, through eNOS downregulation and p38 MAPK activation, and impairs mitochondrial function in metabolically active tissues of dietary obese mice.

Tedesco, Laura; Valerio, Alessandra; Dossena, Marta; Cardile, Annalisa; Ragni, Maurizio; Pagano, Claudio; Pagotto, Uberto; Carruba, Michele O.; Vettor, Roberto; Nisoli, Enzo

2010-01-01

41

Survival in Critical Illness Is Associated with Early Activation of Mitochondrial Biogenesis  

PubMed Central

Rationale: We previously reported outcome-associated decreases in muscle energetic status and mitochondrial dysfunction in septic patients with multiorgan failure. We postulate that survivors have a greater ability to maintain or recover normal mitochondrial functionality. Objectives: To determine whether mitochondrial biogenesis, the process promoting mitochondrial capacity, is affected in critically ill patients. Methods: Muscle biopsies were taken from 16 critically ill patients recently admitted to intensive care (average 1–2 d) and from 10 healthy, age-matched patients undergoing elective hip surgery. Measurements and Main Results: Survival, mitochondrial morphology, mitochondrial protein content and enzyme activity, mitochondrial biogenesis factor mRNA, microarray analysis, and phosphorylated (energy) metabolites were determined. Ten of 16 critically ill patients survived intensive care. Mitochondrial size increased with worsening outcome, suggestive of swelling. Respiratory protein subunits and transcripts were depleted in critically ill patients and to a greater extent in nonsurvivors. The mRNA content of peroxisome proliferator-activated receptor ? coactivator 1-? (transcriptional coactivator of mitochondrial biogenesis) was only elevated in survivors, as was the mitochondrial oxidative stress protein manganese superoxide dismutase. Eventual survivors demonstrated elevated muscle ATP and a decreased phosphocreatine/ATP ratio. Conclusions: Eventual survivors responded early to critical illness with mitochondrial biogenesis and antioxidant defense responses. These responses may partially counteract mitochondrial protein depletion, helping to maintain functionality and energetic status. Impaired responses, as suggested in nonsurvivors, could increase susceptibility to mitochondrial damage and cellular energetic failure or impede the ability to recover normal function. Clinical trial registered with clinical trials.gov (NCT00187824).

Carre, Jane E.; Orban, Jean-Christophe; Re, Lorenza; Felsmann, Karen; Iffert, Wiebke; Bauer, Michael; Suliman, Hagir B.; Piantadosi, Claude A.; Mayhew, Terry M.; Breen, Patrick; Stotz, Martin; Singer, Mervyn

2010-01-01

42

Cardioprotection by acetylcholine: a novel mechanism via mitochondrial biogenesis and function involving the PGC-1? pathway.  

PubMed

Mitochondrial biogenesis disorders appear to play an essential role in cardiac dysfunction. Acetylcholine as a potential pharmacologic agent exerts cardioprotective effects. However, its direct action on mitochondria biogenesis in acute cardiac damage due to ischemia/reperfusion remains unclear. The present study determined the involvement of mitochondrial biogenesis and function in the cardiopotection of acetylcholine in H9c2 cells subjected to hypoxia/reoxygenation (H/R). Our findings demonstrated that acetylcholine treatment on the beginning of reoxygenation improved cell viability in a concentration-dependent way. Consequently, acetylcholine inhibited the mitochondrial morphological abnormalities and caused a significant increase in mitochondrial density, mass, and mitochondrial DNA (mtDNA) copy number. Accordingly, acetylcholine enhanced ATP synthesis, membrane potentials, and activities of mitochondrial complexes in contrast to H/R alone. Furthermore, acetylcholine stimulated the transcriptional activation and protein expression of peroxisome proliferator-activated receptor co-activator 1 alpha (PGC-1?, the central factor for mitochondrial biogenesis) and its downstream targets including nuclear respiration factors and mitochondrial transcription factor A. In addition, acetylcholine activated phosphorylation of AMP-activated protein kinase (AMPK), which was located upstream of PGC-1?. Atropine (muscarinic receptor antagonist) abolished the favorable effects of acetylcholine on mitochondria. Knockdown of PGC-1? or AMPK by siRNA blocked acetylcholine-induced stimulating effects on mtDNA copy number and against cell injury. In conclusion, we suggested, acetylcholine as a mitochondrial nutrient, protected against the deficient mitochondrial biogenesis and function induced by H/R injury in a cellular model through muscarinic receptor-mediated, AMPK/PGC-1?-associated regulatory program, which may be of significance in elucidating a novel mechanism underlying acetylcholine-induced cardioprotection. PMID:23139024

Sun, Lei; Zhao, Mei; Yu, Xiao-Jiang; Wang, Hao; He, Xi; Liu, Jian-Kang; Zang, Wei-Jin

2013-06-01

43

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants  

SciTech Connect

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2005-12-16

44

Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC1  

Microsoft Academic Search

Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription\\/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling

Zhidan Wu; Pere Puigserver; Ulf Andersson; Chenyu Zhang; Guillaume Adelmant; Vamsi Mootha; Amy Troy; Saverio Cinti; Bradford Lowell; Richard C. Scarpulla; Bruce M. Spiegelman

1999-01-01

45

Deletion of mtDNA disrupts mitochondrial function and structure, but not biogenesis  

Microsoft Academic Search

The role of nuclear DNA (nDNA)-encoded proteins in the regulation of mitochondrial fission and fusion has been documented, yet the role of mitochondrial DNA (mtDNA) and encoded proteins in mitochondrial biogenesis remains unknown. Long-term treatment of a lymphoblastoid cell line Molt-4 with ethidium bromide generated mtDNA-deficient rho0 mutants. Depletion of mtDNA in rho0 cells produced functional and morphological changes in

Ekhson Holmuhamedov; Arshad Jahangir; Martin Bienengraeber; Lionel D Lewis; Andre Terzic

2003-01-01

46

Directing Experimental Biology: A Case Study in Mitochondrial Biogenesis  

PubMed Central

Computational approaches have promised to organize collections of functional genomics data into testable predictions of gene and protein involvement in biological processes and pathways. However, few such predictions have been experimentally validated on a large scale, leaving many bioinformatic methods unproven and underutilized in the biology community. Further, it remains unclear what biological concerns should be taken into account when using computational methods to drive real-world experimental efforts. To investigate these concerns and to establish the utility of computational predictions of gene function, we experimentally tested hundreds of predictions generated from an ensemble of three complementary methods for the process of mitochondrial organization and biogenesis in Saccharomyces cerevisiae. The biological data with respect to the mitochondria are presented in a companion manuscript published in PLoS Genetics (doi:10.1371/journal.pgen.1000407). Here we analyze and explore the results of this study that are broadly applicable for computationalists applying gene function prediction techniques, including a new experimental comparison with 48 genes representing the genomic background. Our study leads to several conclusions that are important to consider when driving laboratory investigations using computational prediction approaches. While most genes in yeast are already known to participate in at least one biological process, we confirm that genes with known functions can still be strong candidates for annotation of additional gene functions. We find that different analysis techniques and different underlying data can both greatly affect the types of functional predictions produced by computational methods. This diversity allows an ensemble of techniques to substantially broaden the biological scope and breadth of predictions. We also find that performing prediction and validation steps iteratively allows us to more completely characterize a biological area of interest. While this study focused on a specific functional area in yeast, many of these observations may be useful in the contexts of other processes and organisms.

Hess, David C.; Li, Kai; Caudy, Amy A.; Troyanskaya, Olga G.

2009-01-01

47

Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1? signaling contributing to increased vulnerability in diabetic heart.  

PubMed

Impaired mitochondrial biogenesis causes skeletal muscle damage in diabetes. However, whether and how mitochondrial biogenesis is impaired in the diabetic heart remains largely unknown. Whether adiponectin (APN), a potent cardioprotective molecule, regulates cardiac mitochondrial function has also not been previously investigated. In this study, electron microscopy revealed significant mitochondrial disorders in ob/ob cardiomyocytes, including mitochondrial swelling and cristae disorientation and breakage. Moreover, mitochondrial biogenesis of ob/ob cardiomyocytes is significantly impaired, as evidenced by reduced Ppargc-1a/Nrf-1/Tfam mRNA levels, mitochondrial DNA content, ATP content, citrate synthase activity, complexes I/III/V activity, AMPK phosphorylation, and increased PGC-1? acetylation. Since APN is an upstream activator of AMPK and APN plasma levels are significantly reduced in ob/ob mice, we further tested the hypothesis that reduced APN in ob/ob mice is causatively related to mitochondrial biogenesis impairment. One week of APN treatment of ob/ob mice activated AMPK, reduced PGC-1? acetylation, increased mitochondrial biogenesis, and attenuated mitochondrial disorders. In contrast, knocking out APN inhibited AMPK-PGC-1? signaling and impaired both mitochondrial biogenesis and function. The ob/ob mice exhibited lower survival rates and exacerbated myocardial injury after MI, when compared to controls. APN supplementation improved mitochondrial biogenesis and attenuated MI injury, an effect that was almost completely abrogated by the AMPK inhibitor compound C. In high glucose/high fat treated neonatal rat ventricular myocytes, siRNA-mediated knockdown of PGC-1? blocked gAd-enhanced mitochondrial biogenesis and function and attenuated protection against hypoxia/reoxygenation injury. In conclusion, hypoadiponectinemia impaired AMPK-PGC-1? signaling, resulting in dysfunctional mitochondrial biogenesis that constitutes a novel mechanism for rendering diabetic hearts more vulnerable to enhanced MI injury. PMID:23460046

Yan, Wenjun; Zhang, Haifeng; Liu, Peilin; Wang, Han; Liu, Jingyi; Gao, Chao; Liu, Yi; Lian, Kun; Yang, Lu; Sun, Lu; Guo, Yunping; Zhang, Lijian; Dong, Ling; Lau, Wayne Bond; Gao, Erhe; Gao, Feng; Xiong, Lize; Wang, Haichang; Qu, Yan; Tao, Ling

2013-03-05

48

Stomatin-Like Protein 2 Binds Cardiolipin and Regulates Mitochondrial Biogenesis and Function?  

PubMed Central

Stomatin-like protein 2 (SLP-2) is a widely expressed mitochondrial inner membrane protein of unknown function. Here we show that human SLP-2 interacts with prohibitin-1 and -2 and binds to the mitochondrial membrane phospholipid cardiolipin. Upregulation of SLP-2 expression increases cardiolipin content and the formation of metabolically active mitochondrial membranes and induces mitochondrial biogenesis. In human T lymphocytes, these events correlate with increased complex I and II activities, increased intracellular ATP stores, and increased resistance to apoptosis through the intrinsic pathway, ultimately enhancing cellular responses. We propose that the function of SLP-2 is to recruit prohibitins to cardiolipin to form cardiolipin-enriched microdomains in which electron transport complexes are optimally assembled. Likely through the prohibitin functional interactome, SLP-2 then regulates mitochondrial biogenesis and function.

Christie, Darah A.; Lemke, Caitlin D.; Elias, Isaac M.; Chau, Luan A.; Kirchhof, Mark G.; Li, Bo; Ball, Eric H.; Dunn, Stanley D.; Hatch, Grant M.; Madrenas, Joaquin

2011-01-01

49

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride.  

PubMed

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl?), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl? supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl? supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1? (PGC-1?) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl? supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. PMID:22982409

Saxena, Saurabh; Shukla, Dhananjay; Bansal, Anju

2012-09-08

50

Cybrid Models of Parkinson's Disease Show Variable Mitochondrial Biogenesis and Genotype-Respiration Relationships  

PubMed Central

Sporadic Parkinson's disease (sPD) is a nervous system-wide disease that presents with a bradykinetic movement disorder and frequently progresses to include depression and cognitive impairment. Cybrid models of sPD are based on expression of sPD platelet mitochondrial DNA (mtDNA) in neural cells and demonstrate some similarities to sPD brains. In sPD and CTL cybrids we characterized aspects of mitochondrial biogenesis, mtDNA genomics, composition of the respirasome and the relationships among isolated mitochondrial and intact cell respiration. Cybrid mtDNA levels varied and correlated with expression of PGC-1? a transcriptional co-activator regulator of mitochondrial biogenesis. Levels of mtDNA heteroplasmic mutations were asymmetrically distributed across the mitochondrial genome; numbers of heteroplasmies were more evenly distributed. Neither levels nor numbers of heteroplasmies distinguished sPD from CTL. sPD cybrid mitochondrial ETC subunit protein levels were not altered. Isolated mitochondrial complex I respiration rates showed limited correlation with whole cell complex I respiration rates in both sPD and CTL cybrids. Intact cell respiration during the normoxic-anoxic transition yielded Km values for oxygen that directly related to respiration rates in CTL but not in sPD cell lines. Both sPD and CTL cybrid cells are substantially heterogeneous in mitochondrial genomic and physiologic properties. Our results suggest that mtDNA depletion may occur in sPD neurons and could reflect impairment of mitochondrial biogenesis. Cybrids remain a valuable model for some aspects of sPD but their heterogeneity mitigates against a simple designation of sPD phenotype in this cell model.

Keeney, Paula M.; Dunham, Lisa D.; Quigley, Caitlin K.; Morton, Stephanie L.; Bergquist, Kristen E.; Bennett, James P.

2009-01-01

51

Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis  

PubMed Central

Metabolic stimuli such as insulin and insulin like growth factor cause cellular accumulation of G protein Coupled Receptor Kinase 2 (GRK2), which in turn is able to induce insulin resistance. Here we show that in fibroblasts, GRK2 is able to increase ATP cellular content by enhancing mitochondrial biogenesis; also, it antagonizes ATP loss after hypoxia/reperfusion. Interestingly, GRK2 is able to localize in the mitochondrial outer membrane, possibly through one region within the RGS homology domain and one region within the catalytic domain. In vivo, GRK2 removal from the skeletal muscle results in reduced ATP production and impaired tolerance to ischemia. Our data show a novel sub-cellular localization of GRK2 in the mitochondria and an unexpected role in regulating mitochondrial biogenesis and ATP generation.

Fusco, Anna; Santulli, Gaetano; Sorriento, Daniela; Cipolletta, Ersilia; Garbi, Corrado; Dorn, Gerald W.; Trimarco, Bruno; Feliciello, Antonio; Iaccarino, Guido

2011-01-01

52

Mitochondrial localization unveils a novel role for GRK2 in organelle biogenesis.  

PubMed

Metabolic stimuli such as insulin and insulin like growth factor cause cellular accumulation of G protein coupled receptor kinase 2 (GRK2), which in turn is able to induce insulin resistance. Here we show that in fibroblasts, GRK2 is able to increase ATP cellular content by enhancing mitochondrial biogenesis; also, it antagonizes ATP loss after hypoxia/reperfusion. Interestingly, GRK2 is able to localize in the mitochondrial outer membrane, possibly through one region within the RGS homology domain and one region within the catalytic domain. In vivo, GRK2 removal from the skeletal muscle results in reduced ATP production and impaired tolerance to ischemia. Our data show a novel sub-cellular localization of GRK2 in the mitochondria and an unexpected role in regulating mitochondrial biogenesis and ATP generation. PMID:21983013

Fusco, Anna; Santulli, Gaetano; Sorriento, Daniela; Cipolletta, Ersilia; Garbi, Corrado; Dorn, Gerald W; Trimarco, Bruno; Feliciello, Antonio; Iaccarino, Guido

2011-10-01

53

Exercise-Induced Bronchoconstriction  

MedlinePLUS

Share | « Back to A to Z Listing Exercise-Induced Bronchoconstriction Exercise-Induced Bronchoconstriction, (EIB), often known as exercise-induced asthma, is a narrowing of the airways causing difficulty moving air out ...

54

Redox and Reactive Oxygen Species Regulation of Mitochondrial Cytochrome c Oxidase Biogenesis.  

PubMed

Abstract Significance: Cytochrome c oxidase (COX), the last enzyme of the mitochondrial respiratory chain, is the major oxygen consumer enzyme in the cell. COX biogenesis involves several redox-regulated steps. The process is highly regulated to prevent the formation of pro-oxidant intermediates. Recent Advances: Regulation of COX assembly involves several reactive oxygen species and redox-regulated steps. These include: (i) Intricate redox-controlled machineries coordinate the expression of COX isoenzymes depending on the environmental oxygen concentration. (ii) COX is a heme A-copper metalloenzyme. COX copper metallation involves the copper chaperone Cox17 and several other recently described cysteine-rich proteins, which are oxidatively folded in the mitochondrial intermembrane space. Copper transfer to COX subunits 1 and 2 requires concomitant transfer of redox power. (iii) To avoid the accumulation of reactive assembly intermediates, COX is regulated at the translational level to minimize synthesis of the heme A-containing Cox1 subunit when assembly is impaired. Critical Issues: An increasing number of regulatory pathways converge to facilitate efficient COX assembly, thus preventing oxidative stress. Future Directions: Here we will review on the redox-regulated COX biogenesis steps and will discuss their physiological relevance. Forthcoming insights into the precise regulation of mitochondrial COX biogenesis in normal and stress conditions will likely open future perspectives for understanding mitochondrial redox regulation and prevention of oxidative stress. Antioxid. Redox Signal. 00, 000-000. PMID:22937827

Bourens, Myriam; Fontanesi, Flavia; Soto, Iliana C; Liu, Jingjing; Barrientos, Antoni

2012-10-15

55

Nitric Oxide and Calcium Participate in the Fine Regulation of Mitochondrial Biogenesis in Follicular Thyroid Carcinoma Cells*  

PubMed Central

Members of the peroxisome proliferator-activated receptor ? coactivator-1 family (i.e. PGC-1?, PGC-1?, and the PGC-1-related coactivator (PRC)) are key regulators of mitochondrial biogenesis and function. These regulators serve as mediators between environmental or endogenous signals and the transcriptional machinery governing mitochondrial biogenesis. The FTC-133 and RO82 W-1 follicular thyroid carcinoma cell lines, which present significantly different numbers of mitochondria, metabolic mechanisms, and expression levels of PRC and PGC-1?, may employ retrograde signaling in response to respiratory dysfunction. Nitric oxide (NO) and calcium have been hypothesized to participate in this activity. We investigated the effects of the S-nitroso-N-acetyl-dl-penicillamine-NO donor, on the expression of genes involved in mitochondrial biogenesis and cellular metabolic functions in FTC-133 and RO82 W-1 cells by measuring lactate dehydrogenase and cytochrome c oxidase (COX) activities. We studied the action of ionomycin and 1,2-bis(2-aminophenoxy)ethane-N,N,N?,N?-tetraacetic acid-acetoxymethyl ester (BAPTA/AM) (i.e. a calcium ionophore and a cytosolic calcium chelator) on whole genome expression and mitochondrial biogenesis in RO82 W-1 cells. COX activity and the dynamics of endoplasmic reticulum and mitochondrial networks were analyzed in regard to calcium-modulating treatments. In the FTC-133 and RO82 W-1 cells, the mitochondrial biogenesis induced by NO was mainly related to PRC expression as a retrograde mitochondrial signaling. Ionomycin diminished COX activity and negatively regulated PRC-mediated mitochondrial biogenesis in RO82 W-1 cells, whereas BAPTA/AM produced the opposite effects with a reorganization of the mitochondrial network. This is the first demonstration that NO and calcium regulate mitochondrial biogenesis through the PRC pathway in thyroid cell lines.

Le Pennec, Soazig; Mirebeau-Prunier, Delphine; Boutet-Bouzamondo, Nathalie; Jacques, Caroline; Guillotin, Delphine; Lauret, Emilie; Houlgatte, Remi; Malthiery, Yves; Savagner, Frederique

2011-01-01

56

Short term exercise induces PGC-1?, ameliorates inflammation and increases mitochondrial membrane proteins but fails to increase respiratory enzymes in aging diabetic hearts.  

PubMed

PGC-1?, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1? is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1? on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1? without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNF?) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1? such as NRF-1 and several respiratory genes. Such mismatch between PGC-1? and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1? expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1? mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age. PMID:23936397

Botta, Amy; Laher, Ismail; Beam, Julianne; Decoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L; Ghosh, Sanjoy

2013-08-01

57

Carbon monoxide, skeletal muscle oxidative stress, and mitochondrial biogenesis in humans.  

PubMed

Given that the physiology of heme oxygenase-1 (HO-1) encompasses mitochondrial biogenesis, we tested the hypothesis that the HO-1 product, carbon monoxide (CO), activates mitochondrial biogenesis in skeletal muscle and enhances maximal oxygen uptake (Vo(2max)) in humans. In 10 healthy subjects, we biopsied the vastus lateralis and performed Vo(2max) tests followed by blinded randomization to air or CO breathing (1 h/day at 100 parts/million for 5 days), a contralateral muscle biopsy on day 5, and repeat Vo(2max) testing on day 8. Six independent subjects underwent CO breathing and two muscle biopsies without exercise testing. Molecular studies were performed by real-time RT-PCR, Western blot analysis, and immunochemistry. After Vo(2max) testing plus CO breathing, significant increases were found in mRNA levels for nuclear respiratory factor-1, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, mitochondrial transcription factor-A (Tfam), and DNA polymerase gamma (Polgamma) with no change in mitochondrial DNA (mtDNA) copy number or Vo(2max). Levels of myosin heavy chain I and nuclear-encoded HO-1, superoxide dismutase-2, citrate synthase, mitofusin-1 and -2, and mitochondrial-encoded cytochrome oxidase subunit-I (COX-I) and ATPase-6 proteins increased significantly. None of these responses were reproduced by Vo(2max) testing alone, whereas CO alone increased Tfam and Polgamma mRNA, and COX-I, ATPase-6, mitofusin-2, HO-1, and superoxide dismutase protein. These findings provide evidence linking the HO/CO response involved in mitochondrial biogenesis in rodents to skeletal muscle in humans through a set of responses involving regulation of the mtDNA transcriptosome and mitochondrial fusion proteins autonomously of changes in exercise capacity. PMID:19465554

Rhodes, Michael A; Carraway, Martha Sue; Piantadosi, Claude A; Reynolds, Crystal M; Cherry, Anne D; Wester, T E; Natoli, Michael J; Massey, E Wayne; Moon, Richard E; Suliman, Hagir B

2009-05-22

58

Roles of Oxidative Stress, Apoptosis, PGC-1? and Mitochondrial Biogenesis in Cerebral Ischemia.  

PubMed

The primary physiological function of mitochondria is to generate adenosine triphosphate through oxidative phosphorylation via the electron transport chain. Overproduction of reactive oxygen species (ROS) as byproducts generated from mitochondria have been implicated in acute brain injuries such as stroke from cerebral ischemia. It was well-documented that mitochondria-dependent apoptotic pathway involves pro- and anti-apoptotic protein binding, release of cytochrome c, leading ultimately to neuronal death. On the other hand, mitochondria also play a role to counteract the detrimental effects elicited by excessive oxidative stress. Recent studies have revealed that oxidative stress and the redox state of ischemic neurons are also implicated in the signaling pathway that involves peroxisome proliferative activated receptor-? (PPAR?) co-activator 1? (PGC1-?). PGC1-? is a master regulator of ROS scavenging enzymes including manganese superoxide dismutase 2 and the uncoupling protein 2, both are mitochondrial proteins, and may contribute to neuronal survival. PGC1-? is also involved in mitochondrial biogenesis that is vital for cell survival. Experimental evidence supports the roles of mitochondrial dysfunction and oxidative stress as determinants of neuronal death as well as endogenous protective mechanisms after stroke. This review aims to summarize the current knowledge focusing on the molecular mechanisms underlying cerebral ischemia involving ROS, mitochondrial dysfunction, apoptosis, mitochondrial proteins capable of ROS scavenging, and mitochondrial biogenesis. PMID:22072942

Chen, Shang-Der; Yang, Ding-I; Lin, Tsu-Kung; Shaw, Fu-Zen; Liou, Chia-Wei; Chuang, Yao-Chung

2011-10-21

59

Calcium induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation.  

PubMed

Previous studies have shown that raising cytosolic calcium in myotubes induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha expression and mitochondrial biogenesis. This finding suggests that the increases in cytosolic calcium in skeletal muscle during exercise may mediate the exercise-induced increase in mitochondria. The initial aim of this study was to determine whether raising calcium in skeletal muscle induces the same adaptations as in myotubes. We found that treatment of rat epitrochlearis muscles with a concentration of caffeine that raises cytosolic calcium to a concentration too low to cause contraction induces increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha expression and mitochondrial biogenesis. Our second aim was to elucidate the pathway by which calcium induces these adaptations. Raising cytosolic calcium has been shown to activate calcium/calmodulin-dependent protein kinase in muscle. In the present study raising cytosolic calcium resulted in increases in phosphorylation of p38 mitogen-activated protein kinase and activating transcription factor-2, which were blocked by the calcium/calmodulin-dependent protein kinase inhibitor KN93 and by the p38 mitogen-activated protein kinase inhibitor SB202190. The increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha expression and mitochondrial biogenesis were also prevented by inhibiting p38 activation. We interpret these findings as evidence that p38 mitogen-activated protein kinase is downstream of calcium/calmodulin-dependent protein kinase in a signaling pathway by which increases in cytosolic calcium lead to increases in peroxisome proliferator-activated receptor gamma coactivator-1alpha expression and mitochondrial biogenesis in muscle. PMID:17488713

Wright, David C; Geiger, Paige C; Han, Dong-Ho; Jones, Terry E; Holloszy, John O

2007-05-07

60

Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS  

Microsoft Academic Search

Calorie restriction extends life span in organisms ranging from yeast to mammals. Here, we report that calorie restriction for either 3 or 12 months induced endothelial nitric oxide synthase (eNOS) expression and 3',5'-cyclic guanosine monophosphate formation in various tissues of male mice. This was accompanied by mitochondrial biogenesis, with increased oxygen consumption and adenosine triphosphate production, and an enhanced expression

Enzo Nisoli; Cristina Tonello; Annalisa Cardile; Valeria Cozzi; Renata Bracale; Laura Tedesco; Sestina Falcone; Alessandra Valerio; Orazio Cantoni; Emilio Clementi; Salvador Moncada; Michele O. Carruba

2005-01-01

61

Triiodothyronine induces lipid oxidation and mitochondrial biogenesis in rat Harderian gland.  

PubMed

The rat Harderian gland (HG) is an orbital gland producing a copious lipid secretion. Recent studies indicate that its secretory activity is regulated by thyroid hormones. In this study, we found that both isoforms of the thyroid hormone receptor (Tr? (Thra) and Tr? (Thrb)) are expressed in rat HGs. Although Thra is expressed at a higher level, only Thrb is regulated by triiodothyronine (T3). Because T3 induces an increase in lipid metabolism in rat HGs, we investigated the effects of an animal's thyroid state on the expression levels of carnitine palmitoyltransferase-1A (Cpt1a) and carnitine palmitoyltransferase-1B (Cpt1b) and acyl-CoA oxidase (Acox1) (rate-limiting enzymes in mitochondrial and peroxisomal fatty acid oxidation respectively), as well as on the mitochondrial compartment, thereby correlating mitochondrial activity and biogenesis with morphological analysis. We found that hypothyroidism decreased the expression of Cpt1b and Acox1 mRNA, whereas the administration of T3 to hypothyroid rats increased transcript levels. Respiratory parameters and catalase protein levels provided further evidence that T3 modulates mitochondrial and peroxisomal activities. Furthermore, in hypothyroid rat HGs, the mitochondrial number and their total area decreased with respect to the controls, whereas the average area of the individual mitochondrion did not change. However, the average area of the individual mitochondrion was reduced by ?50% in hypothyroid T3-treated HGs, and the mitochondrial number and the total area of the mitochondrial compartment increased. The mitochondrial morphometric data correlated well with the molecular results. Indeed, hypothyroid status did not modify the expression of mitochondrial biogenesis genes such as Ppargc1a, Nrf1 and Tfam, whereas T3 treatment increased the expression level of these genes. PMID:23873539

Santillo, A; Burrone, L; Falvo, S; Senese, R; Lanni, A; Chieffi Baccari, G

2013-09-09

62

Enhancement of mitochondrial biogenesis with polyphenols: combined effects of resveratrol and equol in human endothelial cells.  

PubMed

Emerging evidence suggests that combinatorial action of numerous biologically active compounds may be a valuable source in a variety of therapeutic applications. Several nutraceuticals have demonstrated to augment the efficacy of pharmacological approaches or provide physiological benefit to improve age-related decline. Recently, the possibilities of anti-ageing interventions have multiplied also to ameliorate the mitochondrial alterations in ageing-associated diseases. In this report, we approached a novel treatment strategy by combining two bioactive dietary constituents (resveratrol and equol) to determine their effect on mitochondrial function. Taking into account that the biological activities of resveratrol and equol has been observed in a wide range of biological processes, they were selected to examine whether combining them would be more effective to modulate mitochondrial function. In HUVEC cells our results demonstrate that the co-administration of these natural products increased mitochondrial mass and mitochondrial DNA content. Additionally, combined use of both compounds increased SIRT1 enzymatic activity and induced mitochondrial biogenesis factors such as PGC1-?, TFAM and NRF-1. Therefore, identification of this novel synergism may provide a new perspective for future treatments aiming to modulate the mitochondrial activity with implications in maintaining endothelial function which is crucial in the regulation of immune response. Further studies to discover the molecular details of this crosstalk and to identify new combinations of active compounds affecting the mitochondrial function will be extremely beneficial to prevent mitochondrial decline. PMID:23842073

Davinelli, Sergio; Sapere, Nadia; Visentin, Manuela; Zella, Davide; Scapagnini, Giovanni

2013-07-11

63

Mechanisms of calcium-induced mitochondrial biogenesis and GLUT4 synthesis.  

PubMed

Regularly performed aerobic exercise leads to increases in skeletal muscle mitochondria and glucose transporter 4 (GLUT4) protein content, resulting in an enhanced capacity to oxidize substrates and improvements in insulin- and contraction-mediated glucose uptake. Although the specific mechanisms governing these adaptive responses have not been fully elucidated, accumulating evidence suggests that the increase in cytosolic Ca2+ that occurs with each wave of sacrolemmal depolarization is a key component of these processes. Treating L6 muscle cells with agents that increase Ca2+ without causing reductions in ~P or the activation of 5'-AMP-activated protein kinase leads to increases in GLUT4 and mitochondrial protein contents. This effect is likely controlled through calcium/calmodulin-dependent protein kinase (CaMK), since KN93, a specific CaMK inhibitor, blocks these adaptive responses. Recent findings provide evidence that the activation of p38 mitogen-activated protein kinase (MAPK) is involved in the pathway through which Ca2+/CaMK mediates mitochondrial and GLUT4 biogenesis. p38 MAPK initiates GLUT4 and mitochondrial biogenesis through the activation of transcription factors and transcriptional coactivators such as myocyte enhancer factor 2 (MEF2) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 alpha). Subsequent increases in the content of these proteins further enhance Ca2+-induced GLUT4 and mitochondrial biogenesis. Since decreases in mitochondrial and GLUT4 contents are associated with skeletal muscle insulin resistance, an understanding of the mechanisms by which these processes can be normalized will aid in the prevention and treatment of type 2 diabetes. PMID:18059607

Wright, David C

2007-10-01

64

Inherited Variants in Mitochondrial Biogenesis Genes May Influence Epithelial Ovarian Cancer Risk  

PubMed Central

Background Mitochondria contribute to oxidative stress, a phenomenon implicated in ovarian carcinogenesis. We hypothesized that inherited variants in mitochondrial-related genes influence epithelial ovarian cancer (EOC) susceptibility. Methods Through a multi-center study of 1,815 Caucasian EOC cases and 1,900 controls, we investigated associations between EOC risk and 128 single nucleotide polymorphisms (SNPs) from 22 genes/regions within the mitochondrial genome (mtDNA) and 2,839 nuclear-encoded SNPs localized to 138 genes involved in mitochondrial biogenesis (BIO, n=35), steroid hormone metabolism (HOR, n=13), and oxidative phosphorylation (OXP, n=90) pathways. Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) between genotype and case status. Overall significance of each gene and pathway was evaluated using Fisher’s method to combine SNP-level evidence. At the SNP-level, we investigated whether lifetime ovulation, hormone replacement therapy (HRT), and cigarette smoking were confounders or modifiers of associations. Results Inter-individual variation involving BIO was most strongly associated with EOC risk (empirical P=0.050), especially for NRF1, MTERF, PPARGC1A, ESRRA, and CAMK2D. Several SNP-level associations strengthened after adjustment for non-genetic factors, particularly for MTERF. Statistical interactions with cigarette smoking and HRT use were observed with MTERF and CAMK2D SNPs, respectively. Overall variation within mtDNA, HOR, and OXP was not statistically significant (empirical P >0.10). Conclusion We provide novel evidence to suggest that variants in mitochondrial biogenesis genes may influence EOC susceptibility. Impact A deeper understanding of the complex mechanisms implicated in mitochondrial biogenesis and oxidative stress may aid in developing strategies to reduce morbidity and mortality from EOC.

Permuth-Wey, Jennifer; Chen, Y. Ann; Tsai, Ya-Yu; Chen, Zhihua; Qu, Xiaotao; Lancaster, Johnathan M.; Stockwell, Heather; Dagne, Getachew; Iversen, Edwin; Risch, Harvey; Barnholtz-Sloan, Jill; Cunningham, Julie M.; Vierkant, Robert A.; Fridley, Brooke L.; Sutphen, Rebecca; McLaughlin, John; Narod, Steven A.; Goode, Ellen L.; Schildkraut, Joellen M.; Fenstermacher, David; Phelan, Catherine M.; Sellers, Thomas A.

2011-01-01

65

Nrf2 promotes alveolar mitochondrial biogenesis and resolution of lung injury in Staphylococcus aureus pneumonia in mice  

PubMed Central

Acute lung injury (ALI) initiates protective responses involving genes downstream of the Nrf2 (Nfe2l2) transcription factor, including heme oxygenase-1 (HO-1), which stimulates mitochondrial biogenesis and related anti-inflammatory processes. We examined mitochondrial biogenesis during Staphylococcus aureus pneumonia in mice and the effect of Nrf2 deficiency on lung mitochondrial biogenesis and resolution of lung inflammation. S. aureus pneumonia established by nasal insufflation of live bacteria was studied in mitochondrial reporter (mt-COX8-GFP) mice, wild-type (WT) mice, and Nrf2?/? mice. Bronchoalveolar lavage, wet/dry ratios, real-time RT-PCR and Western analysis, immunohistochemistry, and fluorescence microscopy were performed on the lung at 0, 6, 24, and 48 h. The mice survived S. aureus inoculations at 5 × 108 CFU despite diffuse lung inflammation and edema, but the Nrf2?/? lung showed increased ALI. In mt-COX8-GFP mice, mitochondrial fluorescence was enhanced in bronchial and alveolar type II (AT2) epithelial cells. WT mice displayed rapid HO-1 upregulation and lower proinflammatory TNF-?, IL-1?, and CCL2 and, especially in AT2 cells, higher anti-inflammatory IL-10 and suppressor of cytokine signaling-3 than Nrf2?/? mice. In the alveolar region, WT but not Nrf2?/? mice showed strongly induced nuclear respiratory factor-1, PGC-1?, mitochondrial transcription factor-A, SOD2, Bnip3, mtDNA copy number, and citrate synthase. These findings indicate that S. aureus pneumonia induces Nrf2-dependent mitochondrial biogenesis in the alveolar region, mainly in AT2 cells. Absence of Nrf2 suppresses the alveolar transcriptional network for mitochondrial biogenesis and anti-inflammation, which worsens ALI. The findings link redox activation of mitochondrial biogenesis to ALI resolution.

Athale, Janhavi; Ulrich, Allison; MacGarvey, Nancy Chou; Bartz, Raquel R.; Welty-Wolf, Karen E.; Suliman, Hagir B.; Piantadosi, Claude A.

2013-01-01

66

Calorie Restriction Increases Muscle Mitochondrial Biogenesis in Healthy Humans  

Microsoft Academic Search

BackgroundCaloric restriction without malnutrition extends life span in a range of organisms including insects and mammals and lowers free radical production by the mitochondria. However, the mechanism responsible for this adaptation are poorly understood.Methods and FindingsThe current study was undertaken to examine muscle mitochondrial bioenergetics in response to caloric restriction alone or in combination with exercise in 36 young (36.8

Anthony E Civitarese; Stacy Carling; Leonie K Heilbronn; Mathew H Hulver; Barbara Ukropcova; Walter A Deutsch; Steven R Smith; Eric Ravussin

2007-01-01

67

Iron–sulphur cluster biogenesis and mitochondrial iron homeostasis  

Microsoft Academic Search

Iron–sulphur clusters are important cofactors for proteins that are involved in many cellular processes, including electron transport, enzymatic catalysis and regulation. The enzymes that catalyse the formation of iron–sulphur clusters are widely conserved from bacteria to humans. Recent studies in model systems and humans reveal that iron–sulphur proteins have important roles in mitochondrial iron homeostasis and in the pathogenesis of

Tracey A. Rouault; Wing-Hang Tong

2005-01-01

68

Myc controls transcriptional regulation of cardiac metabolism and mitochondrial biogenesis in response to pathological stress in mice  

PubMed Central

In the adult heart, regulation of fatty acid oxidation and mitochondrial genes is controlled by the PPAR? coactivator–1 (PGC-1) family of transcriptional coactivators. However, in response to pathological stressors such as hemodynamic load or ischemia, cardiac myocytes downregulate PGC-1 activity and fatty acid oxidation genes in preference for glucose metabolism pathways. Interestingly, despite the reduced PGC-1 activity, these pathological stressors are associated with mitochondrial biogenesis, at least initially. The transcription factors that regulate these changes in the setting of reduced PGC-1 are unknown, but Myc can regulate glucose metabolism and mitochondrial biogenesis during cell proliferation and tumorigenesis in cancer cells. Here we have demonstrated that Myc activation in the myocardium of adult mice increases glucose uptake and utilization, downregulates fatty acid oxidation by reducing PGC-1? levels, and induces mitochondrial biogenesis. Inactivation of Myc in the adult myocardium attenuated hypertrophic growth and decreased the expression of glycolytic and mitochondrial biogenesis genes in response to hemodynamic load. Surprisingly, the Myc-orchestrated metabolic alterations were associated with preserved cardiac function and improved recovery from ischemia. Our data suggest that Myc directly regulates glucose metabolism and mitochondrial biogenesis in cardiac myocytes and is an important regulator of energy metabolism in the heart in response to pathologic stress.

Ahuja, Preeti; Zhao, Peng; Angelis, Ekaterini; Ruan, Hongmei; Korge, Paavo; Olson, Aaron; Wang, Yibin; Jin, Eunsook S.; Jeffrey, F. Mark; Portman, Michael; MacLellan, W. Robb

2010-01-01

69

GPAT2, a mitochondrial outer membrane protein, in piRNA biogenesis in germline stem cells.  

PubMed

piRNA (PIWI-interacting RNA) is a germ cell-specific small RNA in which biogenesis PIWI (P-element wimpy testis) family proteins play crucial roles. MILI (mouse Piwi-like), one of the three mouse PIWI family members, is indispensable for piRNA production, DNA methylation of retrotransposons presumably through the piRNA, and spermatogenesis. The biogenesis of piRNA has been divided into primary and secondary processing pathways; in both of these MILI is involved in mice. To analyze the molecular function of MILI in piRNA biogenesis, we utilized germline stem (GS) cells, which are derived from testicular stem cells and possess a spermatogonial phenotype. We established MILI-null GS cell lines and their revertant, MILI-rescued GS cells, by introducing the Mili gene with Sendai virus vector. Comparison of wild-type, MILI-null, and MILI-rescued GS cells revealed that GS cells were quite useful for analyzing the molecular mechanisms of piRNA production, especially the primary processing pathway. We found that glycerol-3-phosphate acyltransferase 2 (GPAT2), a mitochondrial outer membrane protein for lysophosphatidic acid, bound to MILI using the cells and that gene knockdown of GPAT2 brought about impaired piRNA production in GS cells. GPAT2 is not only one of the MILI bound proteins but also a protein essential for primary piRNA biogenesis. PMID:23611983

Shiromoto, Yusuke; Kuramochi-Miyagawa, Satomi; Daiba, Akito; Chuma, Shinichiro; Katanaya, Ami; Katsumata, Akiko; Nishimura, Ken; Ohtaka, Manami; Nakanishi, Mahito; Nakamura, Toshinobu; Yoshinaga, Koichi; Asada, Noriko; Nakamura, Shota; Yasunaga, Teruo; Kojima-Kita, Kanako; Itou, Daisuke; Kimura, Tohru; Nakano, Toru

2013-04-23

70

Decreased mitochondrial biogenesis in temperature-sensitive cell division cycle mutants of Saccharomyces cerevisiae.  

PubMed

The temperature-sensitive cell division cycle (cdc) G1 mutants cdc28 and cdc35 show decreased mitochondrial volumes with respect to the wild type strain A364A (WT) at the restrictive temperature. Of the three criteria of mitochondrial biogenesis studied, that is, number of mitochondria per cell, relative area of the cell occupied by mitochondria, or relative area of mitochondria occupied by inner membranes, only the second indicator was significantly lower in cdc mutants than in the WT. The mitochondrial inner membranes development did not compensate for the decrease in the organelles volume. Apparently, the reduced mitochondrial biogenesis was not due to the temperature shift because the relative area of the cell occupied by mitochondria was already significantly lower at 25 degrees C in cdc mutants. The specific fluxes of oxygen consumption confirmed that the respiratory capacity of cdc mutants is largely impaired in respect to the WT. Cdc28 and cdc35 mutants of Saccharomyces cerevisiae had been previously shown to exhibit high respiratory quotients (from 3 to 7) in respect to the WT (RQ approximately 1.0), which correlated with carbon and energy uncoupling probably the result of glucose-induced catabolite repression [Aon MA, Mónaco ME, Cortassa S (1995) Exp Cell Res 217, 42-51; Mónaco ME, Valdecantos PA, Aon MA (1995) Exp Cell Res 217, 52-56]. PMID:8528003

Genta, H D; Mónaco, M E; Aon, M A

1995-12-01

71

The novel nuclear gene DSS-1 of Saccharomyces cerevisiae is necessary for mitochondrial biogenesis.  

PubMed

A previously unknown nuclear gene DSS-1 from Saccharomyces cerevisiae was cloned and sequenced. The gene was isolated as a multicopy suppressor of a disruption of the SUV-3 gene coding for a DEAD/H box protein involved in processing and turnover of mitochondrial transcripts. The DSS-1 gene codes for a 970 amino-acid protein of molecular weight 111 kDa and is necessary for mitochondrial biogenesis. Amino-acid sequence analysis indicates the presence of motifs characteristic for Escherichia coli RNase II, the dis3 protein from Schizosaccharomyces pombe, the cyt4 protein participating in RNA processing and turnover in Neurospora crassa mitochondria, and the vacB protein from Shigella flexneri. We suggest that the DSS-1 protein may be a component of the mitochondrial 3'-5' exoribonuclease complex. PMID:8590460

Dmochowska, A; Golik, P; Stepien, P P

1995-07-01

72

Nitric Oxide in Skeletal Muscle: Role on Mitochondrial Biogenesis and Function  

PubMed Central

Nitric oxide (NO) has been implicated in several cellular processes as a signaling molecule and also as a source of reactive nitrogen species (RNS). NO is produced by three isoenzymes called nitric oxide synthases (NOS), all present in skeletal muscle. While neuronal NOS (nNOS) and endothelial NOS (eNOS) are isoforms constitutively expressed, inducible NOS (iNOS) is mainly expressed during inflammatory responses. Recent studies have demonstrated that NO is also involved in the mitochondrial biogenesis pathway, having PGC-1? as the main signaling molecule. Increased NO synthesis has been demonstrated in the sarcolemma of skeletal muscle fiber and NO can also reversibly inhibit cytochrome c oxidase (Complex IV of the respiratory chain). Investigation on cultured skeletal myotubes treated with NO donors, NO precursors or NOS inhibitors have also showed a bimodal effect of NO that depends on the concentration used. The present review will discuss the new insights on NO roles on mitochondrial biogenesis and function in skeletal muscle. We will also focus on potential therapeutic strategies based on NO precursors or analogs to treat patients with myopathies and mitochondrial deficiency.

Tengan, Celia Harumi; Rodrigues, Gabriela Silva; Godinho, Rosely Oliveira

2012-01-01

73

Mitochondrial biogenesis drives a vicious cycle of metabolic insufficiency and mitochondrial DNA deletion mutation accumulation in aged rat skeletal muscle fibers.  

PubMed

Aged muscles possess dysfunctional fibers that contain intracellular expansions of somatically derived mitochondrial DNA deletion mutations. At high abundance, these mutations disrupt the expression of mitochondrially-encoded protein subunits of the electron transport chain resulting in aerobic respiration deficient muscle fiber segments. These fiber segments atrophy and break contributing to the loss of muscle mass and function that occurs with age. By combining micro-dissection of individual muscle fibers with microarray analysis, we observed the response induced within these abnormal muscle fibers and detected an increase in many genes affecting metabolism and metabolic regulation. The transcriptional profile and subsequent protein validation suggested that a non-compensatory program of mitochondrial biogenesis was initiated. We hypothesized that this non-adaptive program of mitochondrial biogenesis was driving mtDNA deletion mutation accumulation. We tested this hypothesis by treating aged rats with ?-Guanidinopropionic acid, a compound that stimulates mitochondrial biogenesis. ?-Guanidinopropionic acid treatment increased muscle mitochondrial genome copy number and resulted in a 3.7 fold increase in the abundance of electron transport chain negative muscle fiber segments. We conclude that in electron transport system abnormal muscle fiber segments, a vicious cycle of metabolic insufficiency and non-compensatory mitochondrial biogenesis drive mtDNA deletion mutation accumulation. PMID:23516592

Herbst, Allen; Johnson, Chad J; Hynes, Kayla; McKenzie, Debbie; Aiken, Judd M

2013-03-13

74

Mitochondrial Biogenesis Drives a Vicious Cycle of Metabolic Insufficiency and Mitochondrial DNA Deletion Mutation Accumulation in Aged Rat Skeletal Muscle Fibers  

PubMed Central

Aged muscles possess dysfunctional fibers that contain intracellular expansions of somatically derived mitochondrial DNA deletion mutations. At high abundance, these mutations disrupt the expression of mitochondrially-encoded protein subunits of the electron transport chain resulting in aerobic respiration deficient muscle fiber segments. These fiber segments atrophy and break contributing to the loss of muscle mass and function that occurs with age. By combining micro-dissection of individual muscle fibers with microarray analysis, we observed the response induced within these abnormal muscle fibers and detected an increase in many genes affecting metabolism and metabolic regulation. The transcriptional profile and subsequent protein validation suggested that a non-compensatory program of mitochondrial biogenesis was initiated. We hypothesized that this non-adaptive program of mitochondrial biogenesis was driving mtDNA deletion mutation accumulation. We tested this hypothesis by treating aged rats with ?-Guanidinopropionic acid, a compound that stimulates mitochondrial biogenesis. ?-Guanidinopropionic acid treatment increased muscle mitochondrial genome copy number and resulted in a 3.7 fold increase in the abundance of electron transport chain negative muscle fiber segments. We conclude that in electron transport system abnormal muscle fiber segments, a vicious cycle of metabolic insufficiency and non-compensatory mitochondrial biogenesis drive mtDNA deletion mutation accumulation.

Herbst, Allen; Johnson, Chad J.; Hynes, Kayla; McKenzie, Debbie; Aiken, Judd M.

2013-01-01

75

Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells.  

PubMed

The multidifferentiation ability of mesenchymal stem cells holds great promise for cell therapy. Numerous studies have focused on the establishment of differentiation protocols, whereas little attention has been paid to the metabolic changes during the differentiation process. Mitochondria, the powerhouse of mammalian cells, vary in their number and function in different cell types with different energy demands, but how these variations are associated with cell differentiation remains elusive. In this study, we investigated the changes of mitochondrial biogenesis and bioenergetic function using human mesenchymal stem cells (hMSCs) because of their well-defined differentiation potentials. Upon osteogenic induction, the copy number of mitochondrial DNA, protein subunits of the respiratory enzymes, oxygen consumption rate, and intracellular ATP content were increased, indicating the upregulation of aerobic mitochondrial metabolism. On the other hand, undifferentiated hMSCs showed higher levels of glycolytic enzymes and lactate production rate, suggesting that hMSCs rely more on glycolysis for energy supply in comparison with hMSC-differentiated osteoblasts. In addition, we observed a dramatic decrease of intracellular reactive oxygen species (ROS) as a consequence of upregulation of two antioxidant enzymes, manganese-dependent superoxide dismutase and catalase. Finally, we found that exogenous H(2)O(2) and mitochondrial inhibitors could retard the osteogenic differentiation. These findings suggested an energy production transition from glycolysis to oxidative phosphorylation in hMSCs upon osteogenic induction. Meanwhile, antioxidant enzymes were concurrently upregulated to prevent the accumulation of intracellular ROS. Together, our findings suggest that coordinated regulation of mitochondrial biogenesis and antioxidant enzymes occurs synergistically during osteogenic differentiation of hMSCs. PMID:18218821

Chen, Chien-Tsun; Shih, Yu-Ru V; Kuo, Tom K; Lee, Oscar K; Wei, Yau-Huei

2008-01-24

76

Physical Exercise Regulates p53 Activity Targeting SCO2 and Increases Mitochondrial COX Biogenesis in Cardiac Muscle with Age  

PubMed Central

The purpose of this study was to outline the timelines of mitochondrial function, oxidative stress and cytochrome c oxidase complex (COX) biogenesis in cardiac muscle with age, and to evaluate whether and how these age-related changes were attenuated by exercise. ICR/CD-1 mice were treated with pifithrin-? (PFT?), sacrificed and studied at different ages; ICR/CD-1 mice at younger or older ages were randomized to endurance treadmill running and sedentary conditions. The results showed that mRNA expression of p53 and its protein levels in mitochondria increased with age in cardiac muscle, accompanied by increased mitochondrial oxidative stress, reduced expression of COX subunits and assembly proteins, and decreased expression of most markers in mitochondrial biogenesis. Most of these age-related changes including p53 activity targeting cytochrome oxidase deficient homolog 2 (SCO2), p53 translocation to mitochondria and COX biogenesis were attenuated by exercise in older mice. PFT?, an inhibitor blocking p53 translocation to mitochondria, increased COX biogenesis in older mice, but not in young mice. Our data suggest that physical exercise attenuates age-related changes in mitochondrial COX biogenesis and p53 activity targeting SCO2 and mitochondria, and thereby induces antisenescent and protective effects in cardiac muscle.

Qi, Zhengtang; He, Jie; Su, Yuhui; He, Qiang; Liu, Jingxia; Yu, Lu; Al-Attas, Omar; Hussain, Tajamul; Ding, Shuzhe; Ji, Liu; Qian, Min

2011-01-01

77

Mitochondrial dynamics, biogenesis, and function are coordinated with the cell cycle by APC/C CDH1.  

PubMed

Cell proliferation is associated with a high rate of aerobic glycolysis, which has been widely interpreted as a compensatory mechanism for suppressed mitochondrial function, despite reports of high respiration rates. The molecular mechanisms that link cell proliferation with mitochondrial metabolism, dynamics, and biogenesis remain obscure. Here, we show that proliferation is associated with an increase in both glycolysis and respiration, in conjunction with mitochondrial fusion and biogenesis. Changes in mitochondrial morphology and mass are due to accumulation of OPA1, MFN1, and TFAM, silencing any of which hinders cell proliferation. Moreover, the levels of OPA1, MFN1, and TFAM are regulated by the ubiquitin ligase APC/C(CDH1), which also controls proteasomal degradation of key glycolytic, glutaminolytic, and cell-cycle proteins. Thus, we have identified an important component of the molecular mechanism that coordinates cell proliferation with activation of the mitochondrial metabolic machinery that provides the necessary energy and biosynthetic substrates. PMID:22482729

Garedew, Assegid; Andreassi, Catia; Moncada, Salvador

2012-04-01

78

AMPK regulation of fatty acid metabolism and mitochondrial biogenesis: implications for obesity.  

PubMed

Skeletal muscle plays an important role in regulating whole-body energy expenditure given it is a major site for glucose and lipid oxidation. Obesity and type 2 diabetes are causally linked through their association with skeletal muscle insulin resistance, while conversely exercise is known to improve whole body glucose homeostasis simultaneously with muscle insulin sensitivity. Exercise activates skeletal muscle AMP-activated protein kinase (AMPK). AMPK plays a role in regulating exercise capacity, skeletal muscle mitochondrial content and contraction-stimulated glucose uptake. Skeletal muscle AMPK is also thought to be important for regulating fatty acid metabolism; however, direct genetic evidence in this area is currently lacking. This review will discuss the current paradigms regarding the influence of AMPK in regulating skeletal muscle fatty acid metabolism and mitochondrial biogenesis at rest and during exercise, and highlight the potential implications in the development of insulin resistance. PMID:22750049

O'Neill, Hayley M; Holloway, Graham P; Steinberg, Gregory R

2012-06-28

79

Dual control of mitochondrial biogenesis by sirtuin 1 and sirtuin 3.  

PubMed

In this review, we discuss the dual control of mitochondrial biogenesis and energy metabolism by silent information regulator-1 and -3 (SIRT1 and SIRT3). SIRT1 activates the peroxisome proliferator activated receptor ? co-activator 1? (PGC-1?)-mediated transcription of nuclear and mitochondrial genes encoding for proteins promoting mitochondria proliferation, oxidative phosphorylation and energy production, whereas SIRT3 directly acts as an activator of proteins important for oxidative phosphorylation, tricarboxylic acid (TCA) cycle and fatty-acid oxidation and indirectly of PGC-1? and AMP-activated protein kinase (AMPK). The complex network involves different cellular compartments, transcriptional activation, post-translational modification and a plethora of secondary effectors. Overall, the mode of interaction between both sirtuin family members may be considered as a prominent case of molecular job-sharing. PMID:23583953

Brenmoehl, Julia; Hoeflich, Andreas

2013-04-11

80

Acetate supplementation increases brain phosphocreatine and reduces AMP levels with no effect on mitochondrial biogenesis.  

PubMed

Acetate supplementation in rats increases plasma acetate and brain acetyl-CoA levels. Although acetate is used as a marker to study glial energy metabolism, the effect that acetate supplementation has on normal brain energy stores has not been quantified. To determine the effect(s) that an increase in acetyl-CoA levels has on brain energy metabolism, we measured brain nucleotide, phosphagen and glycogen levels, and quantified cardiolipin content and mitochondrial number in rats subjected to acetate supplementation. Acetate supplementation was induced with glyceryl triacetate (GTA) by oral gavage (6 g/kg body weight). Rats used for biochemical analysis were euthanized using head-focused microwave irradiation at 2, and 4h following treatment to immediately stop metabolism. We found that acetate did not alter brain ATP, ADP, NAD, GTP levels, or the energy charge ratio [ECR, (ATP+½ ADP)/(ATP+ADP+AMP)] when compared to controls. However, after 4h of treatment brain phosphocreatine levels were significantly elevated with a concomitant reduction in AMP levels with no change in glycogen levels. In parallel studies where rats were treated with GTA for 28 days, we found that acetate did not alter brain glycogen and mitochondrial biogenesis as determined by measuring brain cardiolipin content, the fatty acid composition of cardiolipin and using quantitative ultra-structural analysis to determine mitochondrial density/unit area of cytoplasm in hippocampal CA3 neurons. Collectively, these data suggest that an increase in brain acetyl-CoA levels by acetate supplementation does increase brain energy stores however it has no effect on brain glycogen and neuronal mitochondrial biogenesis. PMID:23321384

Bhatt, Dhaval P; Houdek, Heidi M; Watt, John A; Rosenberger, Thad A

2013-01-12

81

CREB1  Is Recruited to and Mediates Upregulation of the Cytochrome c Promoter during Enhanced Mitochondrial Biogenesis Accompanying Skeletal Muscle Differentiation  

Microsoft Academic Search

To further understand pathways coordinating the expression of nuclear genes encoding mitochondrial proteins, we studied mitochondrial biogenesis during differentiation of myoblasts to myotubes. This energy- demanding process was accompanied by a fivefold increase of ATP turnover, covered by an eightfold increase of mitochondrial activity. While no change in mitochondrial DNA copy number was observed, mRNAs as well as proteins for

Andras Franko; Sabine Mayer; Gerald Thiel; Ludovic Mercy; Thierry Arnould; Hue-Tran Hornig-Do; Rudolf J. Wiesner; Steffi Goffart

2008-01-01

82

Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?  

PubMed Central

Mitochondrial functions include production of energy, activation of programmed cell death, and a number of cell specific tasks, e.g., cell signaling, control of Ca2+ metabolism, and synthesis of a number of important biomolecules. As proper mitochondrial function is critical for normal performance and survival of cells, mitochondrial dysfunction often leads to pathological conditions resulting in various human diseases. Recently mitochondrial dysfunction has been linked to multiple organ failure (MOF) often leading to the death of critical care patients. However, there are two main reasons why this insight did not generate an adequate resonance in clinical settings. First, most data regarding mitochondrial dysfunction in organs susceptible to failure in critical care diseases (liver, kidney, heart, lung, intestine, brain) were collected using animal models. Second, there is no clear therapeutic strategy how acquired mitochondrial dysfunction can be improved. Only the benefit of such therapies will confirm the critical role of mitochondrial dysfunction in clinical settings. Here we summarized data on mitochondrial dysfunction obtained in diverse experimental systems, which are related to conditions seen in intensive care unit (ICU) patients. Particular attention is given to mechanisms that cause cell death and organ dysfunction and to prospective therapeutic strategies, directed to recover mitochondrial function. Collectively the data discussed in this review suggest that appropriate diagnosis and specific treatment of mitochondrial dysfunction in ICU patients may significantly improve the clinical outcome.

2011-01-01

83

Role of Tob55 on mitochondrial protein biogenesis in Trypanosoma brucei  

PubMed Central

Mitochondrial outer membrane (MOM) proteins in parasitic protozoa like Trypanosoma brucei are poorly characterized. In fungi and higher eukaryotes, Tob55 is responsible for the assembly of ?-barrel proteins in the MOM. Here we show that T. brucei Tob55 (TbTob55) has considerable similarity in its primary and secondary structure to Tob55 from other species. TbTob55 is localized in T. brucei MOM and is essential for procyclic cell survival. Induction of Tob55 RNAi decreased the level of the voltage-dependent anion channel (VDAC) within 48 h. Although the primary effect is on VDAC, induction of TbTob55 RNAi for a longer time period also decreased the levels of other nucleus encoded mitochondrial proteins. In addition, the mitochondrial membrane potential was reduced at this later time point possibly due to a reduction in the level of the proteins involved in oxidative phosphorylation. However, mitochondrial structure was not altered due to depletion of Tob55. In vitro protein import of VDAC into mitochondria with a 50-60% reduction of TbTob55 was reduced about 40% in comparison to uninduced control. In addition, the import of presequence-containing proteins such as, cytochrome oxidase subunit 4 (COIV) and trypanosome alternative oxidase (TAO) was affected by about 20 % under this condition. Depletion of VDAC levels by RNAi did not affect the import of either COIV or TAO. Furthermore, TbTob55 over expression increased the steady state level of VDAC as well as the level of the assembled protein complex of VDAC, suggesting that similar to other eukaryotes TbTob55 is involved in assembly of MOM ?-barrel proteins and plays an indirect role in the biogenesis of mitochondrial preproteins destined for the mitochondrial inner membrane.

Sharma, Shvetank; Singha, Ujjal K; Chaudhuri, Minu

2010-01-01

84

Experimental analysis of the rice mitochondrial proteome, its biogenesis, and heterogeneity.  

PubMed

Mitochondria in rice (Oryza sativa) are vital in expanding our understanding of the cellular response to reoxygenation of tissues after anaerobiosis, the crossroads of carbon and nitrogen metabolism, and the role of respiratory energy generation in cytoplasmic male sterility. We have combined density gradient and surface charge purification techniques with proteomics to provide an in-depth proteome of rice shoot mitochondria covering both soluble and integral membrane proteins. Quantitative comparisons of mitochondria purified by density gradients and after further surface charge purification have been used to ensure that the proteins identified copurify with mitochondria and to remove contaminants from the analysis. This rigorous approach to defining a subcellular proteome has yielded 322 nonredundant rice proteins and highlighted contaminants in previously reported rice mitochondrial proteomes. Comparative analysis with the Arabidopsis (Arabidopsis thaliana) mitochondrial proteome reveals conservation of a broad range of known and unknown function proteins in plant mitochondria, with only approximately 20% not having a clear homolog in the Arabidopsis mitochondrial proteome. As in Arabidopsis, only approximately 60% of the rice mitochondrial proteome is predictable using current organelle-targeting prediction tools. Use of the rice protein data set to explore rice transcript data provided insights into rice mitochondrial biogenesis during seed germination, leaf development, and heterogeneity in the expression of nucleus-encoded mitochondrial components in different rice tissues. Highlights include the identification of components involved in thiamine synthesis, evidence for coexpressed and unregulated expression of specific components of protein complexes, a selective anther-enhanced subclass of the decarboxylating segment of the tricarboxylic acid cycle, the differential expression of DNA and RNA replication components, and enhanced expression of specific metabolic components in photosynthetic tissues. PMID:19010998

Huang, Shaobai; Taylor, Nicolas L; Narsai, Reena; Eubel, Holger; Whelan, James; Millar, A Harvey

2008-11-14

85

POTENTIAL ROLE OF NITRIC OXIDE IN CONTRACTION-STIMULATED GLUCOSE UPTAKE AND MITOCHONDRIAL BIOGENESIS IN SKELETAL MUSCLE  

Microsoft Academic Search

Summary 1. This revie ww ill discuss the potential role of nitric oxide (NO) in the (i) regulation of skeletal muscle glucose uptak ed uring exercise and (ii) the acti vation of mitochondrial biogenesis after exercise. 2. We h av e shown in humans that local infusion of a NO synthase (NOS) inhibitor during exercise attenuates increases in skeletal muscle

Glenn K. McConell; Glenn D Wadley

2008-01-01

86

Age-associated declines in mitochondrial biogenesis and protein quality control factors are minimized by exercise training.  

PubMed

A decline in mitochondrial biogenesis and mitochondrial protein quality control in skeletal muscle is a common finding in aging, but exercise training has been suggested as a possible cure. In this report, we tested the hypothesis that moderate-intensity exercise training could prevent the age-associated deterioration in mitochondrial biogenesis in the gastrocnemius muscle of Wistar rats. Exercise training, consisting of treadmill running at 60% of the initial Vo(2max), reversed or attenuated significant age-associated (detrimental) declines in mitochondrial mass (succinate dehydrogenase, citrate synthase, cytochrome-c oxidase-4, mtDNA), SIRT1 activity, AMPK, pAMPK, and peroxisome proliferator-activated receptor gamma coactivator 1-?, UCP3, and the Lon protease. Exercise training also decreased the gap between young and old animals in other measured parameters, including nuclear respiratory factor 1, mitochondrial transcription factor A, fission-1, mitofusin-1, and polynucleotide phosphorylase levels. We conclude that exercise training can help minimize detrimental skeletal muscle aging deficits by improving mitochondrial protein quality control and biogenesis. PMID:22573103

Koltai, Erika; Hart, Nikolett; Taylor, Albert W; Goto, Sataro; Ngo, Jenny K; Davies, Kelvin J A; Radak, Zsolt

2012-05-09

87

Mitochondrial and nuclear mutations that affect the biogenesis of the mitochondrial ribosomes of yeast  

Microsoft Academic Search

We have isolated about five hundred temperature-sensitive mutants specific for the mitochondrial functions. Their growth on glycerol is defective at 36°C and\\/or 20°C. While most of the mutations were nuclearly inherited, about thirty were found to be of mitochondrial origin.

M. Bolotin-Fukuhara

1979-01-01

88

High mitochondrial densities in the hearts of Antarctic icefishes are maintained by an increase in mitochondrial size rather than mitochondrial biogenesis.  

PubMed

We investigated the molecular mechanisms regulating differences in mitochondrial volume density between heart ventricles of Antarctic notothenioids that vary in the expression of hemoglobin (Hb) and myoglobin (Mb). In mammals, peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) and nuclear respiratory factor 1 (NRF-1) stimulate mitochondrial biogenesis and maintain mitochondrial density in muscle tissues. We hypothesized that these factors would also maintain mitochondrial density in the hearts of Antarctic notothenioids. The percent cell volume occupied by mitochondria is significantly lower in hearts of the red-blooded notothenioid Notothenia coriiceps (18.18+/-0.69%) in comparison with those of the icefish Chaenocephalus aceratus (36.53+/-2.07%), which lacks both Hb and cardiac Mb. Mitochondrial densities are not different between hearts of N. coriiceps and Chionodraco rastrospinosus, which lacks Hb, but whose heart expresses Mb. Despite differences in mitochondrial volume density between hearts of N. coriiceps and C. aceratus, the levels of transcripts of the genes encoding PGC-1alpha, NRF-1 and citrate synthase, and the copy number of mitochondrial DNA do not differ. Our results indicate that the high mitochondrial densities in hearts of C. aceratus may result from an increase in organelle size. The surface-to-volume ratio of mitochondria from N. coriiceps is 1.9-fold greater than that of mitochondria from C. aceratus. In addition, the levels of PGC-1alpha correlate with mitochondrial density in muscle tissues of notothenioids possessing mitochondria of similar size and morphology. Finally, the levels of PGC-1alpha are 4.6-fold higher in the aerobic pectoral adductor muscle in comparison with the glycolytic skeletal muscle of N. coriiceps. The potential physiological significance of an increase in mitochondrial size in hearts of Antarctic icefishes is discussed. PMID:18689417

Urschel, Matthew R; O'Brien, Kristin M

2008-08-01

89

The forkhead transcription factor Hcm1 promotes mitochondrial biogenesis and stress resistance in yeast.  

PubMed

In Saccharomyces cerevisiae, the forkhead transcription factor Hcm1 is involved in chromosome segregation, spindle pole dynamics, and budding. We found that Hcm1 interacts with the histone deacetylase Sir2 and shifts from cytoplasm to the nucleus in the G(1)/S phase or in response to oxidative stress stimuli. The nuclear localization of Hcm1 depends on the activity of Sir2 as revealed by activators and inhibitors of the sirtuins and the ?sir2 mutant. Hcm1-overexpressing cells display more mitochondria that can be attributed to increased amounts of Abf2, a protein involved in mitochondrial biogenesis. These cells also show higher rates of oxygen consumption and improved resistance to oxidative stress that would be explained by increased catalase and Sod2 activities and molecular chaperones such as Hsp26, Hsp30, and members of Hsp70 family. Microarray analyses also reveal increased expression of genes involved in mitochondrial energy pathways and those allowing the transition from the exponential to the stationary phase. Taken together, these results describe a new and relevant role of Hcm1 for mitochondrial functions, suggesting that this transcription factor would participate in the adaptation of cells from fermentative to respiratory metabolism. PMID:20847055

Rodriguez-Colman, Maria José; Reverter-Branchat, Gemma; Sorolla, M Alba; Tamarit, Jordi; Ros, Joaquim; Cabiscol, Elisa

2010-09-16

90

A heme-sensing mechanism in the translational regulation of mitochondrial cytochrome c oxidase biogenesis.  

PubMed

Heme plays fundamental roles as cofactor and signaling molecule in multiple pathways devoted to oxygen sensing and utilization in aerobic organisms. For cellular respiration, heme serves as a prosthetic group in electron transfer proteins and redox enzymes. Here we report that in the yeast Saccharomyces cerevisiae, a heme-sensing mechanism translationally controls the biogenesis of cytochrome c oxidase (COX), the terminal mitochondrial respiratory chain enzyme. We show that Mss51, a COX1 mRNA-specific translational activator and Cox1 chaperone, which coordinates Cox1 synthesis in mitoribosomes with its assembly in COX, is a heme-binding protein. Mss51 contains two heme regulatory motifs or Cys-Pro-X domains located in its N terminus. Using a combination of in vitro and in vivo approaches, we have demonstrated that these motifs are important for heme binding and efficient performance of Mss51 functions. We conclude that heme sensing by Mss51 regulates COX biogenesis and aerobic energy production. PMID:23217259

Soto, Iliana C; Fontanesi, Flavia; Myers, Richard S; Hamel, Patrice; Barrientos, Antoni

2012-12-01

91

Mitochondrial and nuclear mutations that affect the biogenesis of the mitochondrial ribosomes of yeast  

Microsoft Academic Search

1.Several nuclear mutants have been isolated which showed thermo-or cryo-sensitive growth on non-fermentable media. Although the original strain carried mitochondrial drug resistance mutations (CR, ER, OR and PR), the resistance to one or several drugs was suppressed in these mutants. Two of them showed a much reduced amount of the mitochondrial small ribosomal subunit (37S) and of the corresponding 16S

Frédéric Sor; Gérard Faye

1979-01-01

92

Lipoamide or lipoic acid stimulates mitochondrial biogenesis in 3T3-L1 adipocytes via the endothelial NO synthase-cGMP-protein kinase G signalling pathway  

PubMed Central

BACKGROUND AND PURPOSE Metabolic dysfunction due to loss of mitochondria plays an important role in diabetes, and stimulation of mitochondrial biogenesis by anti-diabetic drugs improves mitochondrial function. In a search for potent stimulators of mitochondrial biogenesis, we examined the effects and mechanisms of lipoamide and ?-lipoic acid (LA) in adipocytes. EXPERIMENTAL APPROACH Differentiated 3T3-L1 adipocytes were treated with lipoamide or LA. Mitochondrial biogenesis and possible signalling pathways were examined. KEY RESULTS Exposure of 3T3-L1 cells to lipoamide or LA for 24 h increased the number and mitochondrial mass per cell. Such treatment also increased mitochondrial DNA copy number, protein levels and expression of transcription factors involved in mitochondrial biogenesis, including PGC-1?, mitochondrial transcription factor A and nuclear respiratory factor 1. Lipoamide produced these effects at concentrations of 1 and 10 µmol·L?1, whereas LA was most effective at 100 µmol·L?1. At 10 µmol·L?1, lipoamide, but not LA, stimulated mRNA expressions of PPAR-?, PPAR-? and CPT-1?. The potency of lipoamide was 10–100-fold greater than that of LA. Lipoamide dose-dependently stimulated expression of endothelial nitric oxide synthase (eNOS) and formation of cGMP. Knockdown of eNOS (with small interfering RNA) prevented lipoamide-induced mitochondrial biogenesis, which was also blocked by the soluble guanylate cyclase inhibitor, ODQ and the protein kinase G (PKG) inhibitor, KT5823. Thus, stimulation of mitochondrial biogenesis by lipoamide involved signalling via the eNOS-cGMP-PKG pathway. CONCLUSIONS AND IMPLICATIONS Our data suggest that lipoamide is a potent stimulator of mitochondrial biogenesis in adipocyte, and may have potential therapeutic application in obesity and diabetes.

Shen, Weili; Hao, Jiejie; Feng, Zhihui; Tian, Chuan; Chen, Weijun; Packer, Lester; Shi, Xianglin; Zang, Weijin; Liu, Jiankang

2011-01-01

93

Heterogeneity of Mitochondrial Protein Biogenesis during Primary Leaf Development in Barley1  

PubMed Central

The natural developmental gradient of light-grown primary leaves of barley (Hordeum vulgare L.) was used to analyze the biogenesis of mitochondrial proteins in relation to the age and physiological changes within the leaf. The data indicate that the protein composition of mitochondria changes markedly during leaf development. Three distinct patterns of protein development were noted: group A proteins, consisting of the E1 ?-subunit of the pyruvate dehydrogenase complex, ORF156, ORF577, alternative oxidase, RPS12, cytochrome oxidase subunits II and III, malic enzyme, and the ?- and ?-subunits of F1-ATPase; group B proteins, consisting of the E1 ?-subunit of the pyruvate dehydrogenase complex, isocitrate dehydrogenase, HSP70A, cpn60C, and cpn60B; and group C proteins, consisting of the four subunits of the glycine decarboxylase complex (P, H, T, and L proteins), fumarase, and formate dehydrogenase. All of the proteins increased in concentration from the basal meristem to the end of the elongation zone (20.0 mm from the leaf base), whereupon group A proteins decreased, group B proteins increased to a maximum at 50 mm from the leaf base, and group C proteins increased to a maximum at the leaf tip. This study provides evidence of a marked heterogeneity of mitochondrial protein composition, reflecting a changing function as leaf cells develop photosynthetic and photorespiratory capacity.

Thompson, Peter; Bowsher, Caroline G.; Tobin, Alyson K.

1998-01-01

94

A crucial role of the mitochondrial protein import receptor MOM19 for the biogenesis of mitochondria  

PubMed Central

The novel genetic method of "sheltered RIP" (repeat induced point mutation) was used to generate a Neurospora crassa mutant in which MOM19, a component of the protein import machinery of the mitochondrial outer membrane, can be depleted. Deficiency in MOM19 resulted in a severe growth defect, but the cells remained viable. The number of mitochondrial profiles was not grossly changed, but mutant mitochondria were highly deficient in cristae membranes, cytochromes, and protein synthesis activity. Protein import into isolated mutant mitochondria was decreased by factors of 6 to 30 for most proteins from all suborganellar compartments. Proteins like the ADP/ATP carrier, MOM19, and cytochrome c, whose import into wild-type mitochondria occurs independently of MOM19 became imported normally showing that the reduced import activities are solely caused by a lack of MOM19. Depletion of MOM19 reveals a close functional relationship between MOM19 and MOM22, since loss of MOM19 led to decreased levels of MOM22 and reduced protein import through MOM22. Furthermore, MOM72 does not function as a general backup receptor for MOM19 suggesting that these two proteins have distinct precursor specificities. These findings demonstrate that the import receptor MOM19 fulfills an important role in the biogenesis of mitochondria and that it is essential for the formation of mitochondria competent in respiration and phosphorylation.

1994-01-01

95

Defective mitochondrial biogenesis: a hallmark of the high cardiovascular risk in the metabolic syndrome?  

PubMed

The metabolic syndrome is a group of risk factors of metabolic origin that are accompanied by increased risk for type 2 diabetes mellitus and cardiovascular disease. These risk factors include atherogenic dyslipidemia, elevated blood pressure and plasma glucose, and a prothrombotic and proinflammatory state. The condition is progressive and is exacerbated by physical inactivity, advancing age, hormonal imbalance, and genetic predisposition. The metabolic syndrome is a particularly challenging clinical condition because its complex molecular basis is still largely undefined. Impaired cell metabolism has, however, been suggested as a relevant pathophysiological process underlying several clinical features of the syndrome. In particular, defective oxidative metabolism seems to be involved in visceral fat gain and in the development of insulin resistance in skeletal muscle. This suggests that mitochondrial function may be impaired in the metabolic syndrome and, thus, in the consequent cardiovascular disease. We have recently found that mitochondrial biogenesis and function are enhanced by nitric oxide in various cell types and tissues, including cardiac muscle. Increasing evidence suggests that this mediator acts as a metabolic sensor in cardiomyocytes. This implies that a defective production of nitric oxide might be linked to dysfunction of the cardiomyocyte metabolism. Here we summarize some recent findings and propose a hypothesis for the high cardiovascular risk linked to the metabolic syndrome. PMID:17395885

Nisoli, Enzo; Clementi, Emilio; Carruba, Michele O; Moncada, Salvador

2007-03-30

96

The pathophysiology of mitochondrial biogenesis: towards four decades of mitochondrial DNA research.  

PubMed

Mitochondria are with very few exceptions ubiquitous organelles in eukaryotic cells where they are essential for cell life and death. Mitochondria play a central role not only in a variety of metabolic pathways including the supply of the bulk of cellular ATP through oxidative phosphorylation (OXPHOS), but also in complex processes such as development, apoptosis, and aging. Mitochondria contain their own genome that is replicated and expressed within the organelle. It encodes 13 polypeptides all of them components of the OXPHOS system, and thus, the integrity of the mitochondrial DNA (mtDNA) is critical for cellular energy supply. In the past 12 years more than 50 point mutations and around 100 rearrangements in the mtDNA have been associated with human diseases. Also in recent years, several mutations in nuclear genes that encode structural or regulatory factors of the OXPHOS system or the mtDNA metabolism have been described. The development of increasingly powerful techniques and the use of cellular and animal models are opening new avenues in the study of mitochondrial medicine. The detailed molecular characterization of the effects produced by different mutations that cause mitochondrial cytopathies will be critical for designing rational therapeutic strategies for this group of devastating diseases. PMID:11073716

Fernández-Moreno, M A; Bornstein, B; Petit, N; Garesse, R

2000-11-01

97

Aging and Calorie Restriction Oppositely Affect Mitochondrial Biogenesis through TFAM Binding at Both Origins of Mitochondrial DNA Replication in Rat Liver.  

PubMed

Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR) is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18-month-old), 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1? NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins (PRX-SO3) in the ad libitum-fed animals. An unexpected age-related decrease in the mitochondrial proteins peroxiredoxin III (Prx III) and superoxide dismutase 2 (SOD2), usually induced by increased ROS and involved in mitochondrial biogenesis, suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression of these genes with aging. The partial prevention of the decrease in Prx III and SOD2 proteins by CR also supported the preservation of mitochondrial biogenesis in the anti-aging action of CR. To investigate further the age- and CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting a quite different modulation of TFAM binding at both origins of replication in aging and CR. PMID:24058615

Picca, Anna; Pesce, Vito; Fracasso, Flavio; Joseph, Anna-Maria; Leeuwenburgh, Christiaan; Lezza, Angela M S

2013-09-13

98

Aging and Calorie Restriction Oppositely Affect Mitochondrial Biogenesis through TFAM Binding at Both Origins of Mitochondrial DNA Replication in Rat Liver  

PubMed Central

Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR) is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18-month-old), 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1? NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins (PRX-SO3) in the ad libitum-fed animals. An unexpected age-related decrease in the mitochondrial proteins peroxiredoxin III (Prx III) and superoxide dismutase 2 (SOD2), usually induced by increased ROS and involved in mitochondrial biogenesis, suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression of these genes with aging. The partial prevention of the decrease in Prx III and SOD2 proteins by CR also supported the preservation of mitochondrial biogenesis in the anti-aging action of CR. To investigate further the age- and CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting a quite different modulation of TFAM binding at both origins of replication in aging and CR.

Picca, Anna; Pesce, Vito; Fracasso, Flavio; Joseph, Anna-Maria; Leeuwenburgh, Christiaan; Lezza, Angela M. S.

2013-01-01

99

Activation of Mitochondrial Biogenesis by Heme Oxygenase-1-mediated NF-E2-related Factor-2 Induction Rescues Mice from Lethal Staphylococcus aureus Sepsis  

PubMed Central

Rationale: Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2–related factor-2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown. Objectives: To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis. Methods: A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage. Measurements and Main Results: Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2-dependent gene expression and nuclear accumulation of nuclear respiratory factor-1, -2? (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1?; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-? production. By contrast, Nrf2?/? and Akt1?/? mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis. Conclusions: We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy.

MacGarvey, Nancy Chou; Suliman, Hagir B.; Bartz, Raquel R.; Fu, Ping; Withers, Crystal M.; Welty-Wolf, Karen E.

2012-01-01

100

Transducer of regulated CREB-binding proteins (TORCs) induce PGC1 transcription and mitochondrial biogenesis in muscle cells  

Microsoft Academic Search

PGC-1 (peroxisome proliferator-activated receptor coactivator 1) is a master regulator of mitochondrial biogenesis and plays an important role in several other aspects of energy metabolism. To identify upstream regulators of PGC-1 gene transcription, 10,000 human full-length cDNAs were screened for induction of the PGC-1 promoter. A number of activators of PGC-1 transcription were found; the most potent activator was the

Zhidan Wu; Xueming Huang; Yajun Feng; Christoph Handschin; Yan Feng; P. Scott Gullicksen; Olivia Bare; Mark Labow; Bruce Spiegelman; Susan C. Stevenson

2006-01-01

101

Regulation of Mitochondrial Respiratory Chain Biogenesis by Estrogens/Estrogen Receptors and Physiological, Pathological and Pharmacological Implications  

PubMed Central

There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17?-estradiol(E2) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E2-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ER? and ER? and their co-activators on the coordinate regulation of both nuclear DNA- and mitochondrial DNA-encoded genes for MRC proteins. In this paper, we have: 1) comprehensively reviewed studies that reveal a novel role of estrogens and ERs in the regulation of MRC biogenesis; 2) discussed their physiological, pathological and pharmacological implications in the control of cell proliferation and apoptosis in relation to estrogen-mediated carcinogenesis, anticancer drug resistance in human breast cancer cells, neuro-protection for Alzheimer’s disease and Parkinson’s disease in brain, cardiovascular protection in human heart and their beneficial effects in lens physiology related to cataract in the eye; and 3) pointed out new research directions to address the key questions in this important and newly emerging area. We also suggest a novel conceptual approach that will contribute to innovative regimines for the prevention or treatment of a wide variety of medical complications based on E2/ER-mediated MRC biogenesis pathway.

Chen, Jin-Qiang; Cammarata, Patrick R.; Baines, Christopher P.; Yager, James D.

2009-01-01

102

The Transmembrane Prolines of the Mitochondrial ADP/ATP Carrier Are Involved in Nucleotide Binding and Transport and Its Biogenesis*  

PubMed Central

The mitochondrial ADP/ATP carrier (Ancp) is a paradigm of the mitochondrial carrier family, which allows cross-talk between mitochondria, where cell energy is mainly produced, and cytosol, where cell energy is mainly consumed. The members of this family share numerous structural and functional characteristics. Resolution of the atomic structure of the bovine Ancp, in a complex with one of its specific inhibitors, revealed interesting features and suggested the involvement of some particular residues in the movements of the protein to perform translocation of nucleotides from one side of the membrane to the other. They correspond to three prolines located in the odd-numbered transmembrane helices (TMH), Pro-27, Pro-132, and Pro-229. The corresponding residues of the yeast Ancp (Pro-43, Ser-147, and Pro-247) were mutated into alanine or leucine, one at a time and analysis of the various mutants evidenced a crucial role of Pro-43 and Pro-247 during nucleotide transport. Beside, replacement of Ser-147 with proline does not inactivate Ancp and this is discussed in view of the conservation of the three prolines at equivalent positions in the Ancp sequences. These prolines belong to the signature sequences of the mitochondrial carriers and we propose they play a dual role in the mitochondrial ADP/ATP carrier function and biogenesis. Unexpectedly their mutations cause more general effects on mitochondrial biogenesis and morphology, as evidenced by measurements of respiratory rates, cytochrome contents, and also clearly highlighted by fluorescence microscopy.

Babot, Marion; Blancard, Corinne; Pelosi, Ludovic; Lauquin, Guy J.-M.; Trezeguet, Veronique

2012-01-01

103

Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation  

PubMed Central

The quantity and activity of mitochondria vary dramatically in tissues and are modulated in response to changing cellular energy demands and environmental factors. The amount of mitochondrial DNA (mtDNA), which encodes essential subunits of the oxidative phosphorylation complexes required for cellular ATP production, is also tightly regulated, but by largely unknown mechanisms. Using murine T cells as a model system, we have addressed how specific signaling pathways influence mitochondrial biogenesis and mtDNA levels. T cell receptor (TCR) activation results in a large increase in mitochondrial mass and membrane potential and a corresponding increase of mtDNA copy number, indicating the vital role for mitochondrial function for the growth and proliferation of these cells. Independent activation of protein kinase C (via PMA) or calcium-related pathways (via ionomycin) had differential and sub-maximal effects on these mitochondrial parameters, as did activation of naïve T cells with proliferative cytokines. Thus, the robust mitochondrial biogenesis response observed upon TCR activation requires synergy of multiple downstream signaling pathways. One such pathway involves AMP-activated protein kinase (AMPK), which we show has an unprecedented role in negatively regulating mitochondrial biogenesis that is mammalian target of rapamycin (mTOR)-dependent. That is, inhibition of AMPK after TCR signaling commences results in excessive, but uncoordinated mitochondrial proliferation. We propose that mitochondrial biogenesis is not under control of a master regulatory circuit, but rather requires the convergence of multiple signaling pathways with distinct downstream consequences on the organelle’s structure, composition, and function.

D'Souza, Anthony D.; Parikh, Neal; Kaech, Susan M.; Shadel, Gerald S.

2009-01-01

104

Alterations in skeletal muscle indicators of mitochondrial structure and biogenesis in patients with type 2 diabetes and heart failure: effects of epicatechin rich cocoa.  

PubMed

(-)-Epicatechin (Epi), a flavanol in cacao stimulates mitochondrial volume and cristae density and protein markers of skeletal muscle (SkM) mitochondrial biogenesis in mice. Type 2 diabetes mellitus (DM2) and heart failure (HF) are diseases associated with defects in SkM mitochondrial structure/function. A study was implemented to assess perturbations and to determine the effects of Epi-rich cocoa in SkM mitochondrial structure and mediators of biogenesis. Five patients with DM2 and stage II/III HF consumed dark chocolate and a beverage containing approximately 100 mg of Epi per day for 3 months. We assessed changes in protein and/or activity levels of oxidative phosphorylation proteins, porin, mitofilin, nNOS, nitric oxide, cGMP, SIRT1, PGC1?, Tfam, and mitochondria volume and cristae abundance by electron microscopy from SkM. Apparent major losses in normal mitochondria structure were observed before treatment. Epi-rich cocoa increased protein and/or activity of mediators of biogenesis and cristae abundance while not changing mitochondrial volume density. Epi-rich cocoa treatment improves SkM mitochondrial structure and in an orchestrated manner, increases molecular markers of mitochondrial biogenesis resulting in enhanced cristae density. Future controlled studies are warranted using Epi-rich cocoa (or pure Epi) to translate improved mitochondrial structure into enhanced cardiac and/or SkM muscle function. PMID:22376256

Taub, Pam R; Ramirez-Sanchez, Israel; Ciaraldi, Theodore P; Perkins, Guy; Murphy, Anne N; Naviaux, Robert; Hogan, Michael; Maisel, Alan S; Henry, Robert R; Ceballos, Guillermo; Villarreal, Francisco

2011-11-07

105

Differential Expression of PGC-1? and Metabolic Sensors Suggest Age-Dependent Induction of Mitochondrial Biogenesis in Friedreich Ataxia Fibroblasts  

PubMed Central

Background Friedreich's ataxia (FRDA) is a mitochondrial rare disease, which molecular origin is associated with defect in the expression of frataxin. The pathological consequences are degeneration of nervous system structures and cardiomyopathy with necrosis and fibrosis, among others. Principal Findings Using FRDA fibroblasts we have characterized the oxidative stress status and mitochondrial biogenesis. We observed deficiency of MnSOD, increased ROS levels and low levels of ATP. Expression of PGC-1? and mtTFA was increased and the active form of the upstream signals p38 MAPK and AMPK in fibroblasts from two patients. Interestingly, the expression of energetic factors correlated with the natural history of disease of the patients, the age when skin biopsy was performed and the size of the GAA expanded alleles. Furthermore, idebenone inhibit mitochondriogenic responses in FRDA cells. Conclusions The induction of mitochondrial biogenesis in FRDA may be a consequence of the mitochondrial impairment associated with disease evolution. The increase of ROS and the involvement of the oxidative phosphorylation may be an early event in the cell pathophysiology of frataxin deficiency, whereas increase of mitochondriogenic response might be a later phenomenon associated to the individual age and natural history of the disease, being more evident as the patient age increases and disease evolves. This is a possible explanation of heart disease in FRDA.

Garcia-Gimenez, Jose Luis; Gimeno, Amparo; Gonzalez-Cabo, Pilar; Dasi, Francisco; Bolinches-Amoros, Arantxa; Molla, Belen; Palau, Francesc; Pallardo, Federico V.

2011-01-01

106

Mia40 and MINOS act in parallel with Ccs1 in the biogenesis of mitochondrial Sod1.  

PubMed

Superoxide dismutase 1 (Sod1) is a major superoxide-scavenging enzyme in the eukaryotic cell, and is localized in the cytosol and intermembrane space of mitochondria. Sod1 requires its specific chaperone Ccs1 and disulfide bond formation in order to be retained in the intermembrane space. Our study identified a pool of Sod1 that is present in the reduced state in mitochondria that lack Ccs1. We created yeast mutants with mutations in highly conserved amino acid residues corresponding to human mutations that cause amyotrophic lateral sclerosis, and found that some of the mutant proteins were present in the reduced state. These mutant variants of Sod1 were efficiently localized in mitochondria. Localization of the reduced, Ccs1-independent forms of Sod1 relied on Mia40, an essential component of the mitochondrial intermembrane space import and assembly pathway that is responsible for the biogenesis of intermembrane space proteins. Furthermore, the mitochondrial inner membrane organizing system (MINOS), which is responsible for mitochondrial membrane architecture, differentially modulated the presence of reduced Sod1 in mitochondria. Thus, we identified novel mitochondrial players that are possibly involved in pathological conditions caused by changes in the biogenesis of Sod1. PMID:23802566

Varabyova, Aksana; Topf, Ulrike; Kwiatkowska, Paulina; Wrobel, Lidia; Kaus-Drobek, Magdalena; Chacinska, Agnieszka

2013-07-22

107

Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis  

SciTech Connect

Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.

Wu, C.-W. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Ping, Y.-H. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Yen, J.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Chang, C.-Y. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Wang, S.-F. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Yeh, C.-L. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Chi, C.-W. [Department a nd Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan 112 (China); Lee, H.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China) and Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China) and Brain Research Center, University System of Taiwan, Taiwan (China)]. E-mail: hclee2@ym.edu.tw

2007-05-01

108

Exercise-induced rhabdomyolysis.  

PubMed

Rhabdomyolysis is a debilitating condition that promotes muscle breakdown and eventually leads to renal dysfunction if not properly managed. The initial presentation may involve lower-extremity muscles, making the foot and ankle specialist one of the first specialists to recognize and diagnose this condition. Proper management of renal function is the primary concern; however, the underlying muscle breakdown needs to be addressed and the condition managed to prevent future problems. In this article we discuss treatment of a patient with exercise-induced rhabdomyolysis; a rehabilitation regimen is presented whose purpose is to condition muscles in order to prevent recurrence of exercise-induced muscle destruction after an acute event. PMID:17507535

Caban, Gregorio; Marin, Luis; Scavone, Frederick

109

Effects of dairy consumption on SIRT1 and mitochondrial biogenesis in adipocytes and muscle cells  

PubMed Central

Background Recent data from this laboratory suggest that components of dairy foods may serve as activators of SIRT1 (Silent Information Regulator Transcript 1), and thereby participate in regulation of glucose and lipid metabolism. In this study, an ex-vivo/in-vitro approach was used to examine the integrated effects of dairy diets on SIRT1 activation in two key target tissues (adipose and muscle tissue). Methods Serum from overweight and obese subjects fed low or high dairy diets for 28 days was added to culture medium (similar to conditioned media) to treat cultured adipocytes and muscle cells for 48 hours. Results Treatment with high dairy group conditioned media resulted in 40% increased SIRT1 gene expression in both tissues (p < 0.01) and 13% increased enzyme activity in adipose tissue compared to baseline. This was associated with increased gene expression of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1?), nuclear respiratory factor 1 (NRF1), cytochrome oxidase c subunit 7 (Cox 7), NADH dehydrogenase and uncoupling protein 2 (UCP2) in adipocytes as well as uncoupling protein 3 (UCP3), NRF1 and Cox 7 in muscle cells (p < 0.05). Further, direct incubation of physiological concentrations of leucine and its metabolites ?-Ketoisocaproic acid (KIC) and ?-hydroxy-methylbuteric acid (HMB) with recombinant human SIRT1 enzyme resulted in 30 to 50% increase of SIRT1 activity (p < 0.05). Conclusions These data indicate that dairy consumption leads to systemic effects, which may promote mitochondrial biogenesis in key target tissues such as muscle and adipose tissue both by direct activation of SIRT1 as well as by SIRT1-independent pathways.

2011-01-01

110

Exercise-Induced Bronchospasm  

PubMed Central

Context: Exercise-induced bronchospasm (EIB) is a phenomenon of airway narrowing that occurs during or after exercise or physical exertion. This condition has been reported in a range of sporting activities but is most common in participants of cold-weather sports (eg, Nordic skiing) and indoor sports (eg, ice-skating and swimming). Traditionally, the terms exercise induced-asthma (EIA) and EIB have been used interchangeably; however, more recent evidence suggests that these entities are separate and should be described as such, given that their treatments differ. Evidence Acquisition: Literature from 2000 to 2010 was obtained through searches of PubMed, Medline, and Google, with the keywords exercise-induced asthma, exercise-induced bronchospasm, asthma and athlete, and asthma and sport and with an emphasis on the current literature (last 3 to 4 years). Results: Although the current literature suggests a differentiation between EIA and EIB, this differentiation is not always clear, and the terms are still often used interchangeably. This lack of distinction makes it difficult to draw conclusions on optimal diagnosis and treatment of EIB. Conclusion: EIB is prevalent in elite-level athletes, with certain groups being at increased risk. Diagnostic testing should be used when possible, given that recent studies suggest poor correlation between symptoms and testing. The mainstay of treatment remains the use of short-acting ?-adrenergic agonists.

Molis, Marc A.; Molis, Whitney E.

2010-01-01

111

Exercise-induced asthma  

Microsoft Academic Search

An acid-induced, cholinergic esophagobronchial reflex has been described whereby acid refluxing into the esophagus causes bronchospasm. Reports of exertional gastroesophageal acid reflux prompted us to study the possibility that exercise-induced asthma (EIA) could be related to gastroesophageal reflux (GER). Following an overnight fast, 10 athletes with a history of EIA (nine men, one woman; mean age 31) were studied. Continuous

Richard A. Wright; Michael A. Sagatelian; Michael E. Simons; Stephen A. McClave; Thomas M. Roy

1996-01-01

112

Promise of Neurorestoration and Mitochondrial Biogenesis in Parkinson's Disease with Multi Target Drugs: An Alternative to Stem Cell Therapy  

PubMed Central

There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1? (peroxisome proliferator-activated receptor ? coactivator-1?), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis.

Oh, Young J.

2013-01-01

113

The deacetylase enzyme SIRT1 is not associated with oxidative capacity in rat heart and skeletal muscle and its overexpression reduces mitochondrial biogenesis  

PubMed Central

Deacetylation of PGC-1? by SIRT1 is thought to be an important step in increasing PGC-1? transcriptional activity, since in muscle cell lines SIRT1 induces PGC-1? protein expression and mitochondrial biogenesis. We examined the relationship between SIRT1 protein and activity, PGC-1? and markers of mitochondrial density, (a) across a range of metabolically heterogeneous skeletal muscles and the heart, and when mitochondrial biogenesis was stimulated by (b) chronic muscle stimulation (7 days) and (c) AICAR administration (5 days), and finally, (d) we also examined the effects of SIRT1 overexpression on mitochondrial biogenesis and PGC-1?. SIRT1 protein and activity were correlated (r= 0.97). There were negative correlations between SIRT1 protein and PGC-1? (r=?0.95), COX IV (r=?0.94) and citrate synthase (r=?0.97). Chronic muscle stimulation and AICAR upregulated PGC-1? protein (22–159%) and oxidative capacity (COX IV, 20–69%); in each instance SIRT1 protein was downregulated by 20–40%, while SIRT1 intrinsic activity was increased. SIRT1 overexpression in rodent muscle increased SIRT1 protein (+240%) and doubled SIRT1 activity, but PGC-1? (?25%), mtTFA (?14%) and COX IV (?10%) proteins were downregulated. Taken altogether these experiments are not consistent with the notion that SIRT1 protein plays an obligatory regulatory role in the process of PGC-1?-mediated mitochondrial biogenesis in mammalian muscle.

Gurd, Brendon J; Yoshida, Yuko; Lally, James; Holloway, Graham P; Bonen, Arend

2009-01-01

114

The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone.  

PubMed

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. PMID:22814253

Baxter, Kristin Kathleen; Uittenbogaard, Martine; Chiaramello, Anne

2012-07-16

115

Biogenesis of giant mitochondria during insect flight muscle development in the locust, Locusta migratoria (L.). Transcription, translation and copy number of mitochondrial DNA.  

PubMed

The biogenesis of giant mitochondria in flight muscle of Locusta migratoria (L.) was analyzed at the molecular level. During the 2 weeks between the beginning of the last larval stage and the imago capable of sustained flight, individual mitochondria have been shown to enlarge 30-fold and the fractional mitochondrial volume of muscle cells increases fourfold [Brosemer, R.W., Vogell, W. and Bücher, Th. (1963) Biochem. Z. 338, 854-910]. Within the same period, the activity of cytochrome c oxidase, containing subunits encoded on mitochondrial DNA, increased twofold. However, no significant change in mitochondrial DNA copy number, and even a threefold decrease in mitochondrial transcripts, was observed. Mitochondrial translation rate, measured in isolated organelles, was twofold higher in larval muscle, which can be explained only partly by the higher content of mitochondrial RNAs. Thus, rather unusually, in this system of mitochondrial differentiation, the mitochondrial biosynthetic capacity correlates with the rate of organelle biogenesis rather than the steady-state concentration of a marker enzyme. The copy number of mitochondrial DNA does not seem to play a major role in determining either mitochondrial transcript levels or functional mass. PMID:10601845

Sogl, B; Gellissen, G; Wiesner, R J

2000-01-01

116

Training-induced acceleration of O(2) uptake on-kinetics precedes muscle mitochondrial biogenesis in humans.  

PubMed

The effects of 5 weeks of moderate-intensity endurance training on pulmonary oxygen uptake kinetics (V(O(2)) on-kinetics) were studied in 15 healthy men (mean ± SD: age 22.7 ± 1.8 years, body weight 76.4 ± 8.9 kg and maximal V(O(2)) 46.0 ± 3.7 ml kg(-1) min(-1)). Training caused a significant acceleration (P = 0.003) of V(O(2)) on-kinetics during moderate-intensity cycling (time constant of the 'primary' component 30.0 ± 6.6 versus 22.8 ± 5.6 s before and after training, respectively) and a significant decrease (P = 0.04) in the amplitude of the primary component (837 ± 351 versus 801 ± 330 ml min(-1)). No changes in myosin heavy chain distribution, muscle fibre capillarization, level of peroxisome proliferator-activated receptor ? coactivator 1? and other markers of mitochondrial biogenesis (mitochondrial DNA copy number, cytochrome c and cytochrome oxidase subunit I contents) in the vastus lateralis were found after training. A significant downregulation in the content of the sarcoplasmic reticulum ATPase 2 (SERCA2; P = 0.03) and a tendency towards a decrease in SERCA1 (P = 0.055) was found after training. The decrease in SERCA1 was positively correlated (P = 0.05) with the training-induced decrease in the gain of the V(O(2)) on-kinetics (?V(O(2)) at steady state/?power output). In the early stage of training, the acceleration in V(O(2)) on-kinetics during moderate-intensity cycling can occur without enhanced mitochondrial biogenesis or changes in muscle myosin heavy chain distribution and in muscle fibre capillarization. The training-induced decrease of the O(2) cost of cycling could be caused by the downregulation of SERCA pumps. PMID:23204290

Zoladz, Jerzy A; Grassi, Bruno; Majerczak, Joanna; Szkutnik, Zbigniew; Korosty?ski, Micha?; Karasi?ski, Janusz; Kilarski, Wincenty; Korzeniewski, Bernard

2012-11-30

117

Mitochondrial gene therapy improves respiration, biogenesis, and transcription in G11778A Leber's hereditary optic neuropathy and T8993G Leigh's syndrome cells.  

PubMed

Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ?1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. PMID:22390282

Iyer, Shilpa; Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R; Bennett, James P

2012-04-17

118

Mitochondrial Gene Therapy Improves Respiration, Biogenesis, and Transcription in G11778A Leber's Hereditary Optic Neuropathy and T8993G Leigh's Syndrome Cells  

PubMed Central

Abstract Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ?1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future.

Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R.

2012-01-01

119

Yeast Mitochondrial Biogenesis: A Role for the PUF RNA-Binding Protein Puf3p in mRNA Localization  

PubMed Central

The asymmetric localization of mRNA plays an important role in coordinating posttranscriptional events in eukaryotic cells. We investigated the peripheral mitochondrial localization of nuclear-encoded mRNAs (MLR) in various conditions in which the mRNA binding protein context and the translation efficiency were altered. We identified Puf3p, a Pumilio family RNA-binding protein, as the first trans-acting factor controlling the MLR phenomenon. This allowed the characterization of two classes of genes whose mRNAs are translated to the vicinity of mitochondria. Class I mRNAs (256 genes) have a Puf3p binding motif in their 3'UTR region and many of them have their MLR properties deeply affected by PUF3 deletion. Conversely, mutations in the Puf3p binding motif alter the mitochondrial localization of BCS1 mRNA. Class II mRNAs (224 genes) have no Puf3p binding site and their asymmetric localization is not affected by the absence of PUF3. In agreement with a co-translational import process, we observed that the presence of puromycin loosens the interactions between most of the MLR-mRNAs and mitochondria. Unexpectedly, cycloheximide, supposed to solidify translational complexes, turned out to destabilize a class of mRNA-mitochondria interactions. Classes I and II mRNAs, which are therefore transported to the mitochondria through different pathways, correlated with different functional modules. Indeed, Class I genes code principally for the assembly factors of respiratory chain complexes and the mitochondrial translation machinery (ribosomes and translation regulators). Class II genes encode proteins of the respiratory chain or proteins involved in metabolic pathways. Thus, MLR, which is intimately linked to translation control, and the activity of mRNA-binding proteins like Puf3p, may provide the conditions for a fine spatiotemporal control of mitochondrial protein import and mitochondrial protein complex assembly. This work therefore provides new openings for the global study of mitochondria biogenesis.

Delaveau, Thierry; Jourdren, Laurent; Le Crom, Stephane; Lemoine, Sophie; Tanty, Veronique; Devaux, Frederic; Jacq, Claude

2008-01-01

120

Yeast mitochondrial RNase P RNA synthesis is altered in an RNase P protein subunit mutant: insights into the biogenesis of a mitochondrial RNA-processing enzyme.  

PubMed Central

Rpm2p is a protein subunit of Saccharomyces cerevisiae yeast mitochondrial RNase P, an enzyme which removes 5' leader sequences from mitochondrial tRNA precursors. Precursor tRNAs accumulate in strains carrying a disrupted allele of RPM2. The resulting defect in mitochondrial protein synthesis causes petite mutants to form. We report here that alteration in the biogenesis of Rpm1r, the RNase P RNA subunit, is another consequence of disrupting RPM2. High-molecular-weight transcripts accumulate, and no mature Rpm1r is produced. Transcript mapping reveals that the smallest RNA accumulated is extended on both the 5' and 3' ends relative to mature Rpm1r. This intermediate and other longer transcripts which accumulate are also found as low-abundance RNAs in wild-type cells, allowing identification of processing events necessary for conversion of the primary transcript to final products. Our data demonstrate directly that Rpm1r is transcribed with its substrates, tRNA met f and tRNAPro, from a promoter located upstream of the tRNA met f gene and suggest that a portion also originates from a second promoter, located between the tRNA met f gene and RPM1. We tested the possibility that precursors accumulate because the RNase P deficiency prevents the removal of the downstream tRNAPro. Large RPM1 transcripts still accumulate in strains missing this tRNA. Thus, an inability to process cotranscribed tRNAs does not explain the precursor accumulation phenotype. Furthermore, strains with mutant RPM1 genes also accumulate precursor Rpm1r, suggesting that mutations in either gene can lead to similar biogenesis defects. Several models to explain precursor accumulation are presented.

Stribinskis, V; Gao, G J; Sulo, P; Dang, Y L; Martin, N C

1996-01-01

121

Elevated PGC-1? Activity Sustains Mitochondrial Biogenesis and Muscle Function without Extending Survival in a Mouse Model of Inherited ALS  

PubMed Central

SUMMARY The transcriptional coactivator PGC-1? induces multiple effects on muscle, including increased mitochondrial mass and activity. Amyotrophic lateral sclerosis (ALS) is a progressive, fatal, adult-onset neurodegenerative disorder characterized by selective loss of motor neurons and skeletal muscle degeneration. An early event is thought to be denervation-induced muscle atrophy accompanied by alterations in mitochondrial activity and morphology within muscle. We now report that elevation of PGC-1? levels in muscles of mice that develop fatal paralysis from an ALS-causing SOD1 mutant elevates PGC-1?-dependent pathways throughout disease course. Mitochondrial biogenesis and activity are maintained through end-stage disease, accompanied by retention of muscle function, delayed muscle atrophy, and significantly improved muscle endurance even at late disease stages. However, survival was not extended. Therefore, muscle is not a primary target of mutant SOD1-mediated toxicity, but drugs increasing PGC-1? activity in muscle represent an attractive therapy for maintaining muscle function during progression of ALS.

Da Cruz, Sandrine; Parone, Philippe A.; Lopes, Vanda S.; Lillo, Concepcion; McAlonis-Downes, Melissa; Lee, Sandra K.; Vetto, Anne P.; Petrosyan, Susanna; Marsala, Martin; Murphy, Anne N.; Williams, David S.; Spiegelman, Bruce M.; Cleveland, Don W.

2013-01-01

122

Rosiglitazone Induces Mitochondrial Biogenesis in Differentiated Murine 3T3-L1 and C3H/10T1/2 Adipocytes  

PubMed Central

Growing evidence indicates that PPAR? agonists, including rosiglitazone (RSG), induce adipose mitochondrial biogenesis. By systematically analyzing mitochondrial gene expression in two common murine adipocyte models, the current study aimed to further establish the direct role of RSG and capture temporal changes in gene transcription. Microarray profiling revealed that in fully differentiated 3T3-L1 and C3H/10T1/2 adipocytes treated with RSG or DMSO vehicle for 1, 2, 4, 7, 24, and 48?hrs, RSG overwhelmingly increased mitochondrial gene transcripts time dependently. The timing of the increases was consistent with the cascade of organelle biogenesis, that is, initiated by induction of transcription factor(s), followed by increases in the biosynthesis machinery, and then by increases in functional components. The transcriptional increases were further validated by increased mitochondrial staining, citrate synthase activity, and O2 consumption, and were found to be associated with increased adiponectin secretion. The work provided further insight on the mechanism of PPAR?-induced mitochondrial biogenesis in differentiated adipocytes.

Rong, James X.; Klein, Jean-Louis D.; Qiu, Yang; Xie, Mi; Johnson, Jennifer H.; Waters, K. Michelle; Zhang, Vivian; Kashatus, Jennifer A.; Remlinger, Katja S.; Bing, Nan; Crosby, Renae M.; Jackson, Tymissha K.; Witherspoon, Sam M.; Moore, John T.; Ryan, Terence E.; Neill, Sue D.; Strum, Jay C.

2011-01-01

123

Rosiglitazone Induces Mitochondrial Biogenesis in Differentiated Murine 3T3-L1 and C3H/10T1/2 Adipocytes.  

PubMed

Growing evidence indicates that PPAR? agonists, including rosiglitazone (RSG), induce adipose mitochondrial biogenesis. By systematically analyzing mitochondrial gene expression in two common murine adipocyte models, the current study aimed to further establish the direct role of RSG and capture temporal changes in gene transcription. Microarray profiling revealed that in fully differentiated 3T3-L1 and C3H/10T1/2 adipocytes treated with RSG or DMSO vehicle for 1, 2, 4, 7, 24, and 48?hrs, RSG overwhelmingly increased mitochondrial gene transcripts time dependently. The timing of the increases was consistent with the cascade of organelle biogenesis, that is, initiated by induction of transcription factor(s), followed by increases in the biosynthesis machinery, and then by increases in functional components. The transcriptional increases were further validated by increased mitochondrial staining, citrate synthase activity, and O(2) consumption, and were found to be associated with increased adiponectin secretion. The work provided further insight on the mechanism of PPAR?-induced mitochondrial biogenesis in differentiated adipocytes. PMID:22013433

Rong, James X; Klein, Jean-Louis D; Qiu, Yang; Xie, Mi; Johnson, Jennifer H; Waters, K Michelle; Zhang, Vivian; Kashatus, Jennifer A; Remlinger, Katja S; Bing, Nan; Crosby, Renae M; Jackson, Tymissha K; Witherspoon, Sam M; Moore, John T; Ryan, Terence E; Neill, Sue D; Strum, Jay C

2011-10-15

124

Gain-of-function R225Q mutation in AMP-activated protein kinase gamma3 subunit increases mitochondrial biogenesis in glycolytic skeletal muscle.  

PubMed

AMP-activated protein kinase (AMPK) is a heterotrimeric complex, composed of a catalytic subunit (alpha) and two regulatory subunits (beta and gamma), that works as a cellular energy sensor. The existence of multiple heterotrimeric complexes provides a molecular basis for the multiple roles of this highly conserved signaling system. The AMPK gamma3 subunit is predominantly expressed in skeletal muscle, mostly in type II glycolytic fiber types. We determined whether the AMPK gamma3 subunit has a role in signaling pathways that mediate mitochondrial biogenesis in skeletal muscle. We provide evidence that overexpression or ablation of the AMPK gamma3 subunit does not appear to play a critical role in defining mitochondrial content in resting skeletal muscle. However, overexpression of a mutant form (R225Q) of the AMPK gamma3 subunit (Tg-AMPKgamma3(225Q)) increases mitochondrial biogenesis in glycolytic skeletal muscle. These adaptations are associated with an increase in expression of the co-activator PGC-1alpha and several transcription factors that regulate mitochondrial biogenesis, including NRF-1, NRF-2, and TFAM. Succinate dehydrogenase staining, a marker of the oxidative profile of individual fibers, was also increased in transversal skeletal muscle sections of white gastrocnemius muscle from Tg-AMPKgamma3(225Q) mice, independent of changes in fiber type composition. In conclusion, a single nucleotide mutation (R225Q) in the AMPK gamma3 subunit is associated with mitochondrial biogenesis in glycolytic skeletal muscle, concomitant with increased expression of the co-activator PGC-1alpha and several transcription factors that regulate mitochondrial proteins, without altering fiber type composition. PMID:18838377

Garcia-Roves, Pablo M; Osler, Megan E; Holmström, Maria H; Zierath, Juleen R

2008-10-06

125

Exercise-induced asthma.  

PubMed

Exercise-induced asthma (EIA) is a common condition that can impede physical activity, particularly for children, adolescents, and young adults. A detailed patient history can help the physician identify subtle EIA clues such as fatigue or poorer performance than training would predict. A careful physical exam can help rule out conditions that mimic EIA such as respiratory infections or cardiac conditions. Pulmonary function testing is often useful for assessing severity and establishing a baseline for assessing treatment efficacy. Treatment options include nonpharmacologic measures that address the exercise environment and warm-up routines. Several medication options and combinations can help patients avoid symptoms and participate fully in fitness and sports activities. PMID:20086685

Lacroix, V J

1999-11-01

126

Exercise induced pulmonary vasoconstriction.  

PubMed Central

Pulmonary vascular resistance normally falls or remains unchanged during exercise. Seven children with pulmonary hypertension were exercised during cardiac catheterisation after operative correction of ventricular septal defect (6) and truncus arteriosus (1). Except for the presence of moderate pulmonary hypertension, resting haemodynamics in these seven children were similar to those of normal children of equal age, but during exercise the postoperative patients showed a rise rather than a fall (+2% vs -18%) in total pulmonary vascular resistance. Two of the seven children had a substantial increase in pulmonary arteriolar resistance during exercise (from 509 to 715 dyne s cm-5 in one patient and from 606 to 828 dyne s cm-5 in the other). These two patients did not differ from normal children in respect of arterial or mixed venous oxygen saturations or of pH with exercise, nor was left atrial pressure related to the rise in pulmonary resistance. These two patients, however, had only a small rise in cardiac output during exercise (6.8% and 43.1%) in spite of a substantial increase in oxygen consumption (121% and 373%). One of the patients with exercise-induced pulmonary vasoconstriction had an 82% increase in resting pulmonary vascular resistance over a five year period subsequent to her first exercise study. Analysis of these data, and those previously reported, suggests that exercise induced pulmonary vasoconstriction may occur in 10 to 25% of patients who survive correction of certain congenital cardiac defects. The vasoconstriction cannot be attributed to abnormal changes in blood gases or left atrial pressure, and may be an early sign of progressive pulmonary hypertension.

Kulik, T J; Bass, J L; Fuhrman, B P; Moller, J H; Lock, J E

1983-01-01

127

Exercise-induced bronchoconstriction.  

PubMed

Exercise-induced asthma, or more appropriately, exercise-induced bronchoconstriction (EIB), occurs in 80 to 90% of individuals with asthma and in approximately 11% of the general population without asthma. EIB is characterised by post-exercise airways obstruction resulting in reductions in forced expiratory volume in 1 second (FEV(1)) of greater than 10% compared with pre-exercise values. The mechanism of EIB remains elusive, although both cooling and drying of airways play prominent roles. Cold, dry inhaled air during exercise or voluntary hyperventilation is the most potent stimulus for EIB. Inflammatory mediators play central roles in causing the post-exercise airways obstruction. Diagnosis of EIB requires the use of an exercise test. The exercise can be a field or laboratory based test, but should be of relatively high intensity (80 to 90% of maximal heart rate) and duration (at least 5 to 8 minutes). Pre- and post-exercise pulmonary function should be compared, and post exercise pulmonary function determined over 20 to 30 minutes for characterisation of EIB. A pre- to post-exercise drop in FEV(1) of greater than 10% is abnormal. Approaches to treatment of EIB include both nonpharmacological and pharmacological strategies. A light exercise warm up prior to moderate to heavy exercise reduces the severity of EIB. More recently, studies have supported a role for dietary salt as a modifier of the severity of EIB, suggesting that salt restrictive diets should reduce symptoms of EIB. Short acting, inhaled beta(2)-agonists constitute the most used prophylactic treatment for EIB. However, antileukotriene agents are emerging as effective, well tolerated, long-term treatments for EIB. PMID:12149043

Gotshall, Robert W

2002-01-01

128

Metallothionein Abrogates GTP Cyclohydrolase I inhibition-Induced Cardiac Contractile and Morphological Defect: Role of Mitochondrial Biogenesis  

PubMed Central

One key mechanism for endothelial dysfunction is eNOS uncoupling, whereby eNOS generates O2•? rather than NO, due to deficient eNOS cofactor tetrahydrobiopterin (BH4). This study was designed to examine the effect of BH4 deficiency on cardiac morphology and function as well as the impact of metallothionein (MT) on BH4 deficiency-induced abnormalities, if any. FVB and cardiac-specific MT transgenic mice were exposed to 2,4-diamino-6-hydroxy-pyrimidine (DAHP, 10 mmol/l, 3 wks), an inhibitor of the BH4 synthetic enzyme GTP cyclohydrolase I. DAHP reduced plasma BH4 levels by 85% and elevated blood pressure in both FVB and MT mice. Echocardiography found decreased fractional shortening and increased end systolic diameter in DAHP-treated FVB mice. Cardiomyocytes from DAHP-treated FVB mice displayed enhanced O2•? production, contractile and intracellular Ca2+ defects including depressed peak shortening and maximal velocity of shortening/relengthening, prolonged duration of relengthening, reduced intracellular Ca2+ rise and clearance. DAHP triggered mitochondrial swelling/myocardial filament aberrations and mitochondrial O2•? accumulation, assessed by TEM and MitoSOX Red fluorescence, respectively. DAHP also promoted the L-NAME inhibitable O2•? production and eNOS phosphorylation at Thr497. Although MT had little effect on cardiac mechanics and ultrastructure, it attenuated DAHP-induced defects in cardiac function, morphology, O2•? production and eNOS phosphorylation (Thr497). The DAHP-induced cardiomyocyte mechanical responses were alleviated by in vitro BH4 treatment. DAHP inhibited mitochondrial biogenesis, mitochondrial uncoupling protein 2 (UCP2) and chaperone HSP90, all but UCP2 was rescued by MT. Our data suggest a role of BH4 deficiency in cardiac dysfunction and therapeutic potential of antioxidants against eNOS uncoupling in the hearts.

Ceylan-Isik, Asli F.; Guo, Kelly K.; Carlson, Edward C.; Privratsky, Jamie R.; Liao, Song-Jie; Cai, Lu; Chen, Alex F.; Ren, Jun

2009-01-01

129

Why translation counts for mitochondria - retrograde signalling links mitochondrial protein synthesis to mitochondrial biogenesis and cell proliferation.  

PubMed

Organelle biosynthesis is a key requirement for cell growth and division. The regulation of mitochondrial biosynthesis exhibits additional layers of complexity compared with that of other organelles because they contain their own genome and dedicated ribosomes. Maintaining these components requires gene expression to be coordinated between the nucleo-cytoplasmic compartment and mitochondria in order to monitor organelle homeostasis and to integrate the responses to the physiological and developmental demands of the cell. Surprisingly, the parameters that are used to monitor or count mitochondrial abundance are not known, nor are the signalling pathways. Inhibiting the translation on mito-ribosomes genetically or with antibiotics can impair cell proliferation and has been attributed to defects in aerobic energy metabolism, even though proliferating cells rely primarily on glycolysis to fuel their metabolic demands. However, a recent study indicates that mitochondrial translational stress and the rescue mechanisms that relieve this stress cause the defect in cell proliferation and occur before any impairment of oxidative phosphorylation. Therefore, the process of mitochondrial translation in itself appears to be an important checkpoint for the monitoring of mitochondrial homeostasis and might have a role in establishing mitochondrial abundance within a cell. This hypothesis article will explore the evidence supporting a role for mito-ribosomes and translation in a mitochondria-counting mechanism. PMID:24013545

Battersby, Brendan J; Richter, Uwe

2013-09-06

130

Contractile activity-induced mitochondrial biogenesis and mTORC1.  

PubMed

In response to exercise training, or chronic contractile activity, mitochondrial content is known to be enriched within skeletal muscle. However, the molecular mechanisms that mediate this adaptation are incompletely defined. Recently, the protein complex, mammalian target of rapamycin complex 1 (mTORC1), has been identified to facilitate the expression of nuclear genes encoding mitochondrial proteins (NUGEMPs) in resting muscle cells via the interaction of the mTORC1 components, mTOR and raptor, the transcription factor Yin Yang 1, and peroxisome proliferator-activated receptor-? coactivator-1?. It is currently unknown if this mechanism is operative during the increase in mitochondrial content that occurs within skeletal muscle with chronic contractile activity (CCA). Thus we employed a cell culture model of murine skeletal muscle and subjected the myotubes to CCA for 3 h per day for 4 consecutive days in the presence or absence of the mTORC1 inhibitor rapamycin. CCA produced increases in the mitochondrial markers cytochrome oxidase (COX) IV (2.5-fold), Tfam (1.5-fold), and COX activity (1.6-fold). Rapamycin-mediated inhibition of mTORC1 did not suppress these CCA-induced increases in mitochondrial proteins and organelle content. mTORC1 inhibition alone produced a selective upregulation of mitochondrial proteins (COX IV, Tfam), but diminished organelle state 3 respiration. CCA restored this impairment to normal. Our results suggest that mTORC1 activity is not integral for the increase in mitochondrial content elicited by CCA, but is required to maintain mitochondrial function and homeostasis in resting muscle. PMID:22700793

Carter, Heather N; Hood, David A

2012-06-13

131

A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins  

PubMed Central

Iron-sulfur (Fe/S) cluster-containing proteins catalyze a number of electron transfer and metabolic reactions. The components and molecular mechanisms involved in the assembly of the Fe/S clusters have been identified only partially. In eukaryotes, mitochondria have been proposed to execute a crucial task in the generation of intramitochondrial and extramitochondrial Fe/S proteins. Herein, we identify the essential ferredoxin Yah1p of Saccharomyces cerevisiae mitochondria as a central component of the Fe/S protein biosynthesis machinery. Depletion of Yah1p by regulated gene expression resulted in a 30-fold accumulation of iron within mitochondria, similar to what has been reported for other components involved in Fe/S protein biogenesis. Yah1p was shown to be required for the assembly of Fe/S proteins both inside mitochondria and in the cytosol. Apparently, at least one of the steps of Fe/S cluster biogenesis within mitochondria requires reduction by ferredoxin. Our findings lend support to the idea of a primary function of mitochondria in the biosynthesis of Fe/S proteins outside the organelle. To our knowledge, Yah1p is the first member of the ferredoxin family for which a function in Fe/S cluster formation has been established. A similar role may be predicted for the bacterial homologs that are encoded within iron-sulfur cluster assembly (isc) operons of prokaryotes.

Lange, Heike; Kaut, Anita; Kispal, Gyula; Lill, Roland

2000-01-01

132

A subcomplex of human mitochondrial RNase P is a bifunctional methyltransferase--extensive moonlighting in mitochondrial tRNA biogenesis  

PubMed Central

Transfer RNAs (tRNAs) reach their mature functional form through several steps of processing and modification. Some nucleotide modifications affect the proper folding of tRNAs, and they are crucial in case of the non-canonically structured animal mitochondrial tRNAs, as exemplified by the apparently ubiquitous methylation of purines at position 9. Here, we show that a subcomplex of human mitochondrial RNase P, the endonuclease removing tRNA 5? extensions, is the methyltransferase responsible for m1G9 and m1A9 formation. The ability of the mitochondrial tRNA:m1R9 methyltransferase to modify both purines is uncommon among nucleic acid modification enzymes. In contrast to all the related methyltransferases, the human mitochondrial enzyme, moreover, requires a short-chain dehydrogenase as a partner protein. Human mitochondrial RNase P, thus, constitutes a multifunctional complex, whose subunits moonlight in cascade: a fatty and amino acid degradation enzyme in tRNA methylation and the methyltransferase, in turn, in tRNA 5? end processing.

Vilardo, Elisa; Nachbagauer, Christa; Buzet, Aurelie; Taschner, Andreas; Holzmann, Johann; Rossmanith, Walter

2012-01-01

133

Stage and tissue-specific expression of rice OsIsu1 gene encoding a scaffold protein for mitochondrial iron–sulfur-cluster biogenesis  

Microsoft Academic Search

Isu is a scaffold protein involved in mitochondrial iron–sulfur-cluster biogenesis, which affects redox and iron homeostasis\\u000a in human and yeast cells. A BLASTP search identified two putative Isu genes in rice, and we designated one of them as OsIsu1. When expressed in onion epidermal cells, OsIsu1::GFP was localized to the mitochondria. Northern analysis showed that OsIsu1 was down-regulated in iron-deficient

Daisuke Tsugama; Shenkui Liu; Tetsuo Takano

2009-01-01

134

Exercise-Induced Bronchoconstriction Quiz  

MedlinePLUS

Exercise-Induced Bronchoconstriction (also called EIB) is a narrowing of the airways that makes it hard to ... have some narrowing of the airways when they exercise. Some patients will only have narrowing of the ...

135

Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involving in mitochondrial biogenesis  

SciTech Connect

By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA. 20 refs., 1 fig., 2 tabs.

Tiranti, V.; Rossi, G.; DiDonato, S. [Istituto Nazionale Neurologico, Carlo Besta (Italy)] [and others

1995-01-20

136

The Drosophila inner-membrane protein PMI controls crista biogenesis and mitochondrial diameter.  

PubMed

Cristae are mitochondrial inner-membrane structures that concentrate respiratory chain complexes and hence regulate ATP production. Mechanisms controlling crista morphogenesis are poorly understood and few crista determinants have been identified. Among them are the Mitofilins that are required to establish crista junctions and ATP-synthase subunits that bend the membrane at the tips of the cristae. We report here the phenotypic consequences associated with the in vivo inactivation of the inner-membrane protein Pantagruelian Mitochondrion I (PMI) both at the scale of the whole organism, and at the level of mitochondrial ultrastructure and function. We show that flies in which PMI is genetically inactivated experience synaptic defects and have a reduced life span. Electron microscopy analysis of the inner-membrane morphology demonstrates that loss of PMI function increases the average length of mitochondrial cristae in embryonic cells. This phenotype is exacerbated in adult neurons in which cristae form a dense tangle of elongated membranes. Conversely, we show that PMI overexpression is sufficient to reduce crista length in vivo. Finally, these crista defects are associated with impaired respiratory chain activity and increases in the level of reactive oxygen species. Since PMI and its human orthologue TMEM11 are regulators of mitochondrial morphology, our data suggest that, by controlling crista length, PMI influences mitochondrial diameter and tubular shape. PMID:23264743

Macchi, Marc; El Fissi, Najla; Tufi, Roberta; Bentobji, Mélanie; Liévens, Jean-Charles; Martins, L Miguel; Royet, Julien; Rival, Thomas

2012-12-21

137

Green tea polyphenols stimulate mitochondrial biogenesis and improve renal function after chronic cyclosporin a treatment in rats.  

PubMed

Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-? (AS-?) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-? coactivator (PGC)-1?, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-?, ND3, COX-IV, mtDNA copy number, PGC-1? mRNA and protein, decreased acetylated PGC-1?, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB. PMID:23755172

Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Thurman, Ronald G; Lemasters, John J; Schnellmann, Rick G; Zhong, Zhi

2013-06-03

138

A Cardiac-Specific Robotized Cellular Assay Identified Families of Human Ligands as Inducers of PGC-1? Expression and Mitochondrial Biogenesis  

PubMed Central

Background Mitochondrial function is dramatically altered in heart failure (HF). This is associated with a decrease in the expression of the transcriptional coactivator PGC-1?, which plays a key role in the coordination of energy metabolism. Identification of compounds able to activate PGC-1? transcription could be of future therapeutic significance. Methodology/Principal Findings We thus developed a robotized cellular assay to screen molecules in order to identify new activators of PGC-1? in a cardiac-like cell line. This screening assay was based on both the assessment of activity and gene expression of a secreted luciferase under the control of the human PGC-1? promoter, stably expressed in H9c2 cells. We screened part of a library of human endogenous ligands and steroid hormones, B vitamins and fatty acids were identified as activators of PGC-1? expression. The most responsive compounds of these families were then tested for PGC-1? gene expression in adult rat cardiomyocytes. These data highly confirmed the primary screening, and the increase in PGC-1? mRNA correlated with an increase in several downstream markers of mitochondrial biogenesis. Moreover, respiration rates of H9c2 cells treated with these compounds were increased evidencing their effectiveness on mitochondrial biogenesis. Conclusions/Significance Using our cellular reporter assay we could identify three original families, able to activate mitochondrial biogenesis both in cell line and adult cardiomyocytes. This first screening can be extended to chemical libraries in order to increase our knowledge on PGC-1? regulation in the heart and to identify potential therapeutic compounds able to improve mitochondrial function in HF.

Ruiz, Matthieu; Courilleau, Delphine; Jullian, Jean-Christophe; Fortin, Dominique; Ventura-Clapier, Renee; Blondeau, Jean-Paul; Garnier, Anne

2012-01-01

139

Hydroxytyrosol protects against oxidative damage by simultaneous activation of mitochondrial biogenesis and phase II detoxifying enzyme systems in retinal pigment epithelial cells.  

PubMed

Studies in this laboratory have previously shown that hydroxytyrosol, the major antioxidant polyphenol in olives, protects ARPE-19 human retinal pigment epithelial cells from oxidative damage induced by acrolein, an environmental toxin and endogenous end product of lipid oxidation, that occurs at increased levels in age-related macular degeneration lesions. A proposed mechanism for this is that protection by hydroxytyrosol against oxidative stress is conferred by the simultaneous activation of two critically important pathways, viz., induction of phase II detoxifying enzymes and stimulation of mitochondrial biogenesis. Cultured ARPE-19 cells were pretreated with hydroxytyrosol and challenged with acrolein. The protective effects of hydroxytyrosol on key factors of mitochondrial biogenesis and phase II detoxifying enzyme systems were examined. Hydroxytyrosol treatment simultaneously protected against acrolein-induced inhibition of nuclear factor-E2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor coactivator 1 alpha (PPARGC1?) in ARPE-19 cells. The activation of Nrf2 led to activation of phase II detoxifying enzymes, including ?-glutamyl-cysteinyl-ligase, NADPH (nicotinamide adenine dinucleotide phosphate)-quinone-oxidoreductase 1, heme-oxygenase-1, superoxide dismutase, peroxiredoxin and thioredoxin as well as other antioxidant enzymes, while the activation of PPARGC1? led to increased protein expression of mitochondrial transcription factor A, uncoupling protein 2 and mitochondrial complexes. These results suggest that hydroxytyrosol is a potent inducer of phase II detoxifying enzymes and an enhancer of mitochondrial biogenesis. Dietary supplementation of hydroxytyrosol may contribute to eye health by preventing the degeneration of retinal pigment epithelial cells induced by oxidative stress. PMID:20149621

Zhu, Lu; Liu, Zhongbo; Feng, Zhihui; Hao, Jiejie; Shen, Weili; Li, Xuesen; Sun, Lijuan; Sharman, Edward; Wang, Ying; Wertz, Karin; Weber, Peter; Shi, Xianglin; Liu, Jiankang

2010-02-09

140

Chronic electrical stimulation drives mitochondrial biogenesis in skeletal muscle of a lizard, Varanus exanthematicus.  

PubMed

We investigated the capacity for phenotypic plasticity of skeletal muscle from Varanus exanthematicus, the savannah monitor lizard. Iliofibularis muscle from one leg of each lizard was electrically stimulated for 8 weeks. Both stimulated and contralateral control muscles were collected and processed for electron microscopy. We used stereological analysis of muscle cross-sections to quantify the volume densities of contractile elements, sarcoplasmic reticulum, mitochondria and intracellular lipids. We found that mitochondrial volume density was approximately fourfold higher in the stimulated muscle compared to controls, which were similar to previously reported values. Sarcoplasmic reticulum volume density was reduced by an amount similar to the increase in mitochondrial volume density while the volume density of contractile elements remained unchanged. Intracellular lipid accumulation was visibly apparent in many stimulated muscle sections but the volume density of lipids did not reach a significant difference. Although monitor lizards lack the highly developed aerobic metabolism of mammals, they appear to possess the capacity for muscle plasticity. PMID:17872989

Schaeffer, Paul J; Nichols, Scott D; Lindstedt, Stan L

2007-10-01

141

Impaired Mitochondrial Biogenesis Precedes Heart Failure in Right Ventricular Hypertrophy in Congenital Heart Disease  

PubMed Central

Background The outcome of the surgical repair in congenital heart disease (CHD) correlates with the degree of myocardial damage. In this study we determined whether mitochondrial DNA depletion is a sensitive marker of right ventricular (RV) damage and whether impaired mitochondrial DNA (mtDNA) replication contributes to the transition from compensated hypertrophy to failure. Methods and Results RV samples obtained from 31 patients undergoing cardiac surgery were compared to 5 RV samples from non-failing hearts (control). Patients were divided into compensated hypertrophy and failure groups based on preoperative echocardiography, catheterization and/or MRI data. Mitochondrial enzyme activities (citrate synthase and succinate dehydrogenase) were maintained during hypertrophy and decreased by ~40% (p<0.05 vs. control) at the stage of failure. In contrast, mtDNA content was progressively decreased in the hypertrophied RV through failure (by 28±8% and 67±11% respectively, p<0.05 for both), whereas mtDNA encoded gene expression was sustained by increased transcriptional activity during compensated hypertrophy but not in failure. MtDNA depletion was attributed to reduced mtDNA replication in both hypertrophied and failing RV and it was independent of PGC-1 down-regulation but was accompanied by reduced expression of proteins constituting the mtDNA replication fork. Decreased mtDNA content in compensated hypertrophy was also associated with pathological changes of mitochondria ultrastructure. Conclusions Impaired mtDNA replication causes early and progressive depletion of mtDNA in the RV of the CHD patients during the transition from hypertrophy to failure. Decreased mtDNA content is likely a sensitive marker of mitochondrial injury in this patient population.

Karamanlidis, Georgios; Bautista-Hernandez, Victor; Fynn-Thompson, Francis; Nido, Pedro del; Tian, Rong

2011-01-01

142

Maternal exercise during pregnancy affects mitochondrial enzymatic activity and biogenesis in offspring brain.  

PubMed

The present study addresses whether exercise during pregnancy in mouse alters mitochondrial function in the brains of the resultant offspring. We divided pregnant mice into four groups: a control group and groups of mice that exercised for 20 (E20m), 30 (E30m) and 40 min/d (E40m). The pregnant mice ran on a treadmill at 12 m/min, 5 d/week for a duration of 3 weeks. The protein expression of cytochrome c oxidase subunit Va (CVa) was downregulated in the offspring of the E20m group, unlike that in the control animals, whereas CVa expression was reserved in the E40m neonates. The F1-ATPase catalytic core (Core) protein expression levels were the highest in the E40m group neonates. Complex I, IV and ATPase activities were significantly lower in the E20m group than that in the control group neonates and were reserved in the E30m and E40m group neonates. The activities of citrate synthase and pyruvate dehydrogenase were consistent with those of complex I, IV and ATPase. Peroxisome proliferator-activated receptor-gamma coactivator 1-alpha, mitochondrial transcription factor A, nuclear respiratory factor-1 and mitochondrial DNA showed high levels of expression in the E40m neonates compared with the other groups. Malondialdehyde (MDA) levels in E40m neonates were higher than that in the controls but were lower than that in the E20m neonates. Finally, 40 min/d of maternal exercise improved mitochondrial function in the resultant pups and was concomitant with brain-derived trophic factor induction in the hippocampus, thereby functionally improving short-term memory. PMID:23227820

Park, Jong-Won; Kim, Mun-Hee; Eo, Su-Ju; Lee, Eun-Ho; Kang, Jong-Suk; Chang, Hyuk-Ki; Leem, Yea-Hyun

2013-01-11

143

Biogenesis of the preprotein translocase of the outer mitochondrial membrane: protein kinase A phosphorylates the precursor of Tom40 and impairs its import  

PubMed Central

The preprotein translocase of the outer mitochondrial membrane (TOM) functions as the main entry gate for the import of nuclear-encoded proteins into mitochondria. The major subunits of the TOM complex are the three receptors Tom20, Tom22, and Tom70 and the central channel-forming protein Tom40. Cytosolic kinases have been shown to regulate the biogenesis and activity of the Tom receptors. Casein kinase 2 stimulates the biogenesis of Tom22 and Tom20, whereas protein kinase A (PKA) impairs the receptor function of Tom70. Here we report that PKA exerts an inhibitory effect on the biogenesis of the ?-barrel protein Tom40. Tom40 is synthesized as precursor on cytosolic ribosomes and subsequently imported into mitochondria. We show that PKA phosphorylates the precursor of Tom40. The phosphorylated Tom40 precursor is impaired in import into mitochondria, whereas the nonphosphorylated precursor is efficiently imported. We conclude that PKA plays a dual role in the regulation of the TOM complex. Phosphorylation by PKA not only impairs the receptor activity of Tom70, but it also inhibits the biogenesis of the channel protein Tom40.

Rao, Sanjana; Schmidt, Oliver; Harbauer, Angelika B.; Schonfisch, Birgit; Guiard, Bernard; Pfanner, Nikolaus; Meisinger, Chris

2012-01-01

144

Pioglitazone Enhances Mitochondrial Biogenesis and Ribosomal Protein Biosynthesis in Skeletal Muscle in Polycystic Ovary Syndrome  

PubMed Central

Insulin resistance is a common metabolic abnormality in women with PCOS and leads to an elevated risk of type 2 diabetes. Studies have shown that thiazolidinediones (TZDs) improve metabolic disturbances in PCOS patients. We hypothesized that the effect of TZDs in PCOS is, in part, mediated by changes in the transcriptional profile of muscle favoring insulin sensitivity. Using Affymetrix microarrays, we examined the effect of pioglitazone (30 mg/day for 16 weeks) on gene expression in skeletal muscle of 10 obese women with PCOS metabolically characterized by a euglycemic-hyperinsulinemic clamp. Moreover, we explored gene expression changes between these PCOS patients before treatment and 13 healthy women. Treatment with pioglitazone improved insulin-stimulated glucose metabolism and plasma adiponectin, and reduced fasting serum insulin (all P<0.05). Global pathway analysis using Gene Map Annotator and Pathway Profiler (GenMAPP 2.1) and Gene Set Enrichment Analysis (GSEA 2.0.1) revealed a significant upregulation of genes representing mitochondrial oxidative phosphorylation (OXPHOS), ribosomal proteins, mRNA processing reactome, translation factors, and proteasome degradation in PCOS after pioglitazone therapy. Quantitative real-time PCR suggested that upregulation of OXPHOS genes was mediated by an increase in PGC-1? expression (P<0.05). Pretreatment expression of genes representing OXPHOS and ribosomal proteins was down-regulated in PCOS patients compared to healthy women. These data indicate that pioglitazone therapy restores insulin sensitivity, in part, by a coordinated upregulation of genes involved in mitochondrial OXPHOS and ribosomal protein biosynthesis in muscle in PCOS. These transcriptional effects of pioglitazone may contribute to prevent the onset of type 2 diabetes in these women.

Skov, Vibe; Glintborg, Dorte; Knudsen, Steen; Tan, Qihua; Jensen, Thomas; Kruse, Torben A.; Beck-Nielsen, Henning; H?jlund, Kurt

2008-01-01

145

Adolescents and Exercise Induced Asthma  

ERIC Educational Resources Information Center

|This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)|

Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

2008-01-01

146

Adolescents and Exercise Induced Asthma  

ERIC Educational Resources Information Center

This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)

Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

2008-01-01

147

Exercise-induced muscle damage and immune cell apoptosis  

Microsoft Academic Search

The purpose of this study was to examine the effect of unaccustomed downhill running on muscle damage, oxidative stress and leukocyte apoptosis. Additionally, four pro-\\/anti- apoptotic proteins, representing the receptor mediated or mitochondrial apoptotic pathway, were assessed to provide insight into the mechanisms involved in exercise-induced apoptosis. Twelve moderately trained subjects aged 18-26 yr performed three 40 min treadmill exercises

Kyung-Shin Park; Darlene A. Sedlock; James W. Navalta; Herbert L. Weith

2006-01-01

148

Sex-dependent differences in rat brown adipose tissue mitochondrial biogenesis and insulin signaling parameters in response to an obesogenic diet.  

PubMed

Marked sex-dependent differences in mitochondrial function and redox status have been found in brown adipose tissue (BAT) of control rats. Insulin also plays a role in the development and maintenance of this tissue. The aim was to investigate sexual dimorphism in the effects of diet-induced obesity on BAT mitochondrial function, as well as on insulin signaling pathway. 10-week-old Wistar rats of both sexes were fed a control diet or a palatable high-fat diet for 26 weeks. Serum markers of insulin sensitivity were analyzed. Mitochondrial DNA (mtDNA) content, mitochondrial oxidative activities, PGC-1? mRNA levels, as well as the protein levels of insulin receptor subunit ? (IR?), glucose transporter GLUT4, ?(3)-adrenergic receptor (?(3)-AR), phosphatidylinositol 3-kinase, mitochondrial transcription factor A (TFAM), cytochrome c oxidase subunit IV (COX IV), and uncoupling protein 1 (UCP1) were measured in BAT. Obese females showed impaired systemic insulin sensitivity accompanied by diminished IR?, GLUT4, and ?(3)-AR protein levels in BAT. In addition, TFAM and COX IV protein and PGC-1? mRNA levels decreased in obese females, whereas mtDNA levels increased. In obese males, oxidative and thermogenic capacities rose and no significant changes were observed in the insulin signaling pathway elements. The reduction of the insulin signaling pathway in BAT of obese females may be responsible, at least partially, for the impaired biogenesis process, which could favor the increase of body weight found in this sex. In contrast, the enhanced mitochondrial functionality in the BAT of males would avoid increased oxidative damage and the impairment of insulin signaling. PMID:23108789

Nadal-Casellas, A; Bauzá-Thorbrügge, M; Proenza, A M; Gianotti, M; Lladó, I

2012-10-29

149

Endurance exercise is protective for mice with mitochondrial myopathy.  

PubMed

Defects in the mitochondrial ATP-generating system are one of the most commonly inherited neurological disorders, but they remain without treatment. We have recently shown that modulation of the peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) level in skeletal muscle of a mitochondrial myopathy mouse model offers a therapeutic approach. Here we analyzed if endurance exercise, which is known to be associated with an increased PGC-1alpha level in muscle, offers the same beneficial effect. We subjected male and female mice that develop a severe mitochondrial myopathy due to a cytochrome-c oxidase deficiency at 3 mo of age to endurance exercise training and monitored phenotypical and metabolic changes. Sedentary myopathy and wild-type mice were used as controls. Exercise increased PGC-1alpha in muscle, resulting in increased mitochondrial biogenesis, and successfully stimulated residual respiratory capacity in muscle tissue. As a consequence, ATP levels were increased in exercised mice compared with sedentary myopathy animals, which resulted in a delayed onset of the myopathy and a prolonged lifespan of the exercised mice. As an added benefit, endurance exercise induced antioxidant enzymes. The overall protective effect of endurance exercise delayed the onset of the mitochondrial myopathy and increased life expectancy in the mouse model. Thus stimulating residual oxidative phosphorylation function in the affected muscle by inducing mitochondrial biogenesis through endurance exercise might offer a valuable therapeutic intervention for mitochondrial myopathy patients. PMID:19286571

Wenz, Tina; Diaz, Francisca; Hernandez, Dayami; Moraes, Carlos T

2009-03-12

150

PPR2263, a DYW-Subgroup Pentatricopeptide Repeat Protein, Is Required for Mitochondrial nad5 and cob Transcript Editing, Mitochondrion Biogenesis, and Maize Growth[C][W  

PubMed Central

RNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain–containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize.

Sosso, Davide; Mbelo, Sylvie; Vernoud, Vanessa; Gendrot, Ghislaine; Dedieu, Annick; Chambrier, Pierre; Dauzat, Myriam; Heurtevin, Laure; Guyon, Virginie; Takenaka, Mizuki; Rogowsky, Peter M.

2012-01-01

151

PPR2263, a DYW-Subgroup Pentatricopeptide repeat protein, is required for mitochondrial nad5 and cob transcript editing, mitochondrion biogenesis, and maize growth.  

PubMed

RNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain-containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize. PMID:22319053

Sosso, Davide; Mbelo, Sylvie; Vernoud, Vanessa; Gendrot, Ghislaine; Dedieu, Annick; Chambrier, Pierre; Dauzat, Myriam; Heurtevin, Laure; Guyon, Virginie; Takenaka, Mizuki; Rogowsky, Peter M

2012-02-07

152

Food related, exercise induced anaphylaxis.  

PubMed Central

Four children under 12 years of age with food dependent, exercise induced anaphylaxis (EIAn) were investigated. These children and five controls performed exercise challenges when fasting and one hour after a meal without food suspected to predispose to the reaction. Patients then performed exercise tests after intake of each suspected food. Three out of 15 food-exercise combination challenges were positive, but no reactions were provoked after exercise without prior intake of suspected foods. Patients underwent skin prick tests to foods and serum total and specific IgE antibodies were measured. Skin prick test results were positive and RAST results were positive in two of three instances. In case 3, food-exercise combination challenges did not provoke any clinical reaction. The diagnosis of food dependent EIAn should be considered in young children with EIAn of unknown origin.

Caffarelli, C; Terzi, V; Perrone, F; Cavagni, G

1996-01-01

153

Dual Location of the Mitochondrial Preprotein Transporters B14.7 and Tim23-2 in Complex I and the TIM17:23 Complex in Arabidopsis Links Mitochondrial Activity and Biogenesis[C][W][OA  

PubMed Central

Interactions between the respiratory chain and protein import complexes have been previously reported in Saccharomyces cerevisiae, but the biological significance of such interactions remains unknown. Characterization of two mitochondrial preprotein and amino acid transport proteins from Arabidopsis thaliana, NADH dehydrogenase B14.7 like (B14.7 [encoded by At2g42210]) and Translocase of the inner membrane subunit 23-2 (Tim23-2 [encoded by At1g72750]), revealed both proteins are present in respiratory chain complex I and the Translocase of the Inner Membrane 17:23. Whereas depletion of B14.7 by T-DNA insertion is lethal, Tim23-2 can be depleted without lethality. Subtle overexpression of Tim23-2 results in a severe delayed growth phenotype and revealed an unexpected, inverse correlation between the abundance of Tim23-2 and the abundance of respiratory complex I. This newly discovered relationship between protein import and respiratory function was confirmed through the investigation of independent complex I knockout mutants, which were found to have correspondingly increased levels of Tim23-2. This increase in Tim23-2 was also associated with delayed growth phenotypes, increased abundance of other import components, and an increased capacity for mitochondrial protein import. Analysis of the Tim23-2–overexpressing plants through global quantitation of transcript abundance and in-organelle protein synthesis assays revealed widespread alterations in transcript abundance of genes encoding mitochondrial proteins and altered rates of mitochondrial protein translation, indicating a pivotal relationship between the machinery of mitochondrial biogenesis and mitochondrial function.

Wang, Yan; Carrie, Chris; Giraud, Estelle; Elhafez, Dina; Narsai, Reena; Duncan, Owen; Whelan, James; Murcha, Monika W.

2012-01-01

154

Activation of the Human Mitochondrial Transcription Factor A Gene by Nuclear Respiratory Factors: A Potential Regulatory Link Between Nuclear and Mitochondrial Gene Expression in Organelle Biogenesis  

Microsoft Academic Search

Mitochondrial transcription factor A (mtTFA), the product of a nuclear gene, stimulates transcription from the two divergent mitochondrial promoters and is likely the principal activator of mitochondrial gene expression in vertebrates. Here we establish that the proximal promoter of the human mtTFA gene is highly dependent upon recognition sites for the nuclear respiratory factors, NRF-1 and NRF-2, for activity. These

Joseph V. Virbasius; Richard C. Scarpulla

1994-01-01

155

Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae: multiple trans-acting nuclear genes exert specific effects on expression of each of the cytochrome c oxidase subunits encoded on mitochondrial DNA.  

PubMed

Fourteen nuclear complementation groups of mutants that specifically affect the three mitochondrially-encoded subunits of yeast cytochrome c oxidase have been characterized. Genes represented by these complementation groups are not required for mitochondrial transcription, transcript processing, or translation per se but are required for the expression of one of the three genes--COX1, COX2, or COX3--which encode the cytochrome c oxicase subunits I, II, or III, respectively. Five of these genes affect the biogenesis of cytochrome c oxidase subunit I, 3 affect the biogenesis of subunit II, 3 affect the biogenesis of subunit III and 3 affect the biogenesis of both cytochrome c oxidase subunit I and cytochrome b, the product of COB. Among the 5 complementation groups of mutants that affect the expression of COX1, 2 lack COX1 transcripts, 1 produces incompletely processed COX1 transcripts, and 2 contain normal levels of normal-sized COX1 transcripts. In contrast, all 3 complementation groups which affect the expression of COX2 and all 3 complementation groups which affect the expression of COX3 exhibit no, or little, detectable difference with respect to the wild type pattern of transcripts. The 3 complementation groups which affect the expression of both COX1 and COB all have aberrant COX1 and COB transcript patterns. These findings indicate that multiple trans-acting nuclear genes are required for specific expression of each COX gene encoded on mitochondrial DNA and suggest that their products act at different steps in the expression of these mitochondrial genes. PMID:2833360

Kloeckener-Gruissem, B; McEwen, J E; Poyton, R O

1987-01-01

156

Biogenesis of Mitochondria: Analysis of Deletion of Mitochondrial Antibiotic Resistance Markers in Petite Mutants of Saccharomyces cerevisiae1  

PubMed Central

Yeast strains carrying markers in several mitochondrial antibiotic resistance loci have been employed in a study of the retention and deletion of mitochondrial genes in cytoplasmic petite mutants. An assessment is made of the results in terms of the probable arrangement and linkage of mitochondrial genetic markers. The results are indicative of the retention of continuous stretches of the mitochondrial genome in most petite mutants, and it is therefore possible to propose a gene order based on co-retention of different markers. The order par, mik1, oli1 is suggested from the petite studies in the case of three markers not previously assigned an unambiguous order by analysis of mitochondrial gene recombination. The frequency of separation of markers by deletion in petites was of an order similar to that obtained by recombination in polar crosses, except in the case of the ery1 and cap1 loci, which were rarely separated in petite mutants. The deletion or retention of the locus determining polarity of recombination (?) was also demonstrated and shown to coincide with deletion or retention of the ery1, cap1 region of the mitochondrial genome. Petites retaining this region, when crossed with rho+ strains, display features of polarity of recombination and transmission similar to the parent rho+ strain. By contrast a petite determined to have lost the ?+ locus did not show normal polarity of marker transmission. Differences were observed in the relative frequency of retention of markers in a number of strains and also when comparing petites derived spontaneously with those obtained after ultraviolet light mutagenesis. By contrast, a similar pattern of marker retention was seen when comparing spontaneous with ethidium bromide-induced petites.

Molloy, P. L.; Linnane, Anthony W.; Lukins, H. B.

1975-01-01

157

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit  

PubMed Central

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle.

He, J.; Cooper, H. M.; Reyes, A.; Di Re, M.; Kazak, L.; Wood, S. R.; Mao, C. C.; Fearnley, I. M.; Walker, J. E.; Holt, I. J.

2012-01-01

158

Berberine protects against high fat diet-induced dysfunction in muscle mitochondria by inducing SIRT1-dependent mitochondrial biogenesis  

Microsoft Academic Search

Berberine (BBR) has recently been shown to improve insulin sensitivity in rodent models of insulin resistance. Although this effect was explained partly through an observed activation of AMP-activated protein kinase (AMPK), the upstream and downstream mediators of this phenotype were not explored. Here, we show that BBR supplementation reverts mitochondrial dysfunction induced by High Fat Diet (HFD) and hyperglycemia in

Ana P. Gomes; Filipe V. Duarte; Patricia Nunes; Basil P. Hubbard; João S. Teodoro; Ana T. Varela; John G. Jones; David A. Sinclair; Carlos M. Palmeira; Anabela P. Rolo

159

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats  

Microsoft Academic Search

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance

Hyun Woo Jeong; Si Young Cho; Shinae Kim; Eui Seok Shin; Jae Man Kim; Min Jeong Song; Pil Joon Park; Jong Hee Sohn; Hyon Park; Dae-Bang Seo; Wan Gi Kim; Sang-Jun Lee

2012-01-01

160

A practical model of low-volume high-intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms.  

PubMed

High-intensity interval training (HIT) induces skeletal muscle metabolic and performance adaptations that resemble traditional endurance training despite a low total exercise volume. Most HIT studies have employed 'all out', variable-load exercise interventions (e.g. repeated Wingate tests) that may not be safe, practical and/or well tolerated by certain individuals. Our purpose was to determine the performance, metabolic and molecular adaptations to a more practical model of low-volume HIT. Seven men (21 + or - 0.4 years, V(O2peak) = 46 + or - 2 ml kg(-1) min(-1)) performed six training sessions over 2 weeks. Each session consisted of 8-12 x 60 s intervals at approximately 100% of peak power output elicited during a ramp V(O2) peak test (355 + or - 10 W) separated by 75 s of recovery. Training increased exercise capacity, as assessed by significant improvements on both 50 kJ and 750 kJ cycling time trials (P < 0.05 for both). Skeletal muscle (vastus lateralis) biopsy samples obtained before and after training revealed increased maximal activity of citrate synthase (CS) and cytochrome c oxidase (COX) as well as total protein content of CS, COX subunits II and IV, and the mitochondrial transcription factor A (Tfam) (P < 0.05 for all). Nuclear abundance of peroxisome proliferator-activated receptor gamma co-activator 1alpha (PGC-1alpha) was approximately 25% higher after training (P < 0.05), but total PGC-1alpha protein content remained unchanged. Total SIRT1 content, a proposed activator of PGC-1alpha and mitochondrial biogenesis, was increased by approximately 56% following training (P < 0.05). Training also increased resting muscle glycogen and total GLUT4 protein content (both P < 0.05). This study demonstrates that a practical model of low volume HIT is a potent stimulus for increasing skeletal muscle mitochondrial capacity and improving exercise performance. The results also suggest that increases in SIRT1, nuclear PGC-1alpha, and Tfam may be involved in coordinating mitochondrial adaptations in response to HIT in human skeletal muscle. PMID:20100740

Little, Jonathan P; Safdar, Adeel; Wilkin, Geoffrey P; Tarnopolsky, Mark A; Gibala, Martin J

2010-01-25

161

Purple sweet potato color attenuates domoic acid-induced cognitive deficits by promoting estrogen receptor-?-mediated mitochondrial biogenesis signaling in mice.  

PubMed

Recent findings suggest that endoplasmic reticulum stress may be involved in the pathogenesis of domoic acid-induced neurodegeneration. Purple sweet potato color, a class of naturally occurring anthocyanins, has beneficial health and biological effects. Recent studies have also shown that anthocyanins have estrogenic activity and can enhance estrogen receptor-? expression. In this study, we evaluated the effect of purple sweet potato color on cognitive deficits induced by hippocampal mitochondrial dysfunction in domoic acid-treated mice and explored the potential mechanisms underlying this effect. Our results showed that the oral administration of purple sweet potato color to domoic acid-treated mice significantly improved their behavioral performance in a step-through passive avoidance task and a Morris water maze task. These improvements were mediated, at least in part, by a stimulation of estrogen receptor-?-mediated mitochondrial biogenesis signaling and by decreases in the expression of p47phox and gp91phox. Decreases in reactive oxygen species and protein carbonylation were also observed, along with a blockade of the endoplasmic reticulum stress pathway. Furthermore, purple sweet potato color significantly suppressed endoplasmic reticulum stress-induced apoptosis, which prevented neuron loss and restored the expression of memory-related proteins. However, knockdown of estrogen receptor-? using short hairpin RNA only partially blocked the neuroprotective effects of purple sweet potato color in the hippocampus of mice cotreated with purple sweet potato color and domoic acid, indicating that purple sweet potato color acts through multiple pathways. These results suggest that purple sweet potato color could be a possible candidate for the prevention and treatment of cognitive deficits in excitotoxic and other brain disorders. PMID:22178976

Lu, Jun; Wu, Dong-mei; Zheng, Yuan-lin; Hu, Bin; Cheng, Wei; Zhang, Zi-feng

2011-11-23

162

Mitochondrial copper metabolism in yeast: mutational analysis of Sco1p involved in the biogenesis of cytochrome c oxidase  

Microsoft Academic Search

Saccharomyces cerevisiae Sco1p is believed to be involved in the transfer of copper from the carrier Cox17p to the mitochondrial cytochrome c oxidase subunits 1 and 2. We here report on the results of a mutational analysis of Sco1p. The two cysteine residues of a\\u000a potential metal-binding motif (CxxxC) are essential for protein function as shown by their substitution by

Anja Rentzsch; Gaby Krummeck-Weiß; Angelika Hofer; Anne Bartuschka; Kai Ostermann; Gerhard Rödel

1999-01-01

163

Acetyl-L-carnitine activates the peroxisome proliferator-activated receptor-? coactivators PGC-1?/PGC-1?-dependent signaling cascade of mitochondrial biogenesis and decreases the oxidized peroxiredoxins content in old rat liver.  

PubMed

The behavior of the peroxisome proliferator-activated receptor-? coactivators PGC-1?/PGC-?-dependent mitochondrial biogenesis signaling pathway, as well as the level of some antioxidant enzymes and proteins involved in mitochondrial dynamics in the liver of old rats before and after 2 months of acetyl-L-carnitine (ALCAR) supplementation, was tested. The results reveal that ALCAR treatment is able to reverse the age-associated decline of PGC-1?, PGC-1?, nuclear respiratory factor 1 (NRF-1), mitochondrial transcription factor A (TFAM), nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 1 (ND1), and cytochrome c oxidase subunit IV (COX IV) protein levels, of mitochondrial DNA (mtDNA) content, and of citrate synthase activity. Moreover, it partially reverses the mitochondrial superoxide dismutase 2 (SOD2) decline and reduces the cellular content of oxidized peroxiredoxins. These data demonstrate that ALCAR treatment is able to promote in the old rat liver a new mitochondrial population that can contribute to the cellular oxidative stress reduction. Furthermore, a remarkable decline of Drp1 and of Mfn2 proteins is reported here for the first time, suggesting a reduced mitochondrial dynamics in aging liver with no effect of ALCAR treatment. PMID:22533417

Pesce, Vito; Nicassio, Luigi; Fracasso, Flavio; Musicco, Clara; Cantatore, Palmiro; Gadaleta, Maria Nicola

2012-04-01

164

Assessment of Mitochondrial Biogenesis and mTORC1 Signaling During Chronic Rapamycin Feeding in Male and Female Mice.  

PubMed

Chronic inhibition of the protein synthesis regulator mTORC1 through rapamycin extends life span in mice, with longer extension in females than in males. Whether rapamycin treatment inhibits protein synthesis or whether it does so differently between sexes has not been examined. UM-HET3 mice were fed a control or rapamycin-supplemented (Rap) diet for 12 weeks. Protein synthesis in mixed, cytosolic (cyto), and mitochondrial (mito) fractions and DNA synthesis and mTORC1 signaling were determined in skeletal muscle, heart, and liver. In both sexes, mito protein synthesis was maintained in skeletal muscle from Rap despite decreases in mixed and cyto fractions, DNA synthesis, and rpS6 phosphorylation. In the heart, no change in protein synthesis occurred despite the decreased DNA synthesis. In the heart and liver, Rap males were more sensitive to mTORC1 inhibition than Rap females. In conclusion, we show changes in protein synthesis and mTORC1 signaling that differ by sex and tissue. PMID:23657975

Drake, Joshua C; Peelor, Frederick F; Biela, Laurie M; Watkins, Molly K; Miller, Richard A; Hamilton, Karyn L; Miller, Benjamin F

2013-05-08

165

Increased fatigue resistance linked to Ca2+-stimulated mitochondrial biogenesis in muscle fibres of cold-acclimated mice.  

PubMed

Mammals exposed to a cold environment initially generate heat by repetitive muscle activity (shivering). Shivering is successively replaced by the recruitment of uncoupling protein-1 (UCP1)-dependent heat production in brown adipose tissue. Interestingly, adaptations observed in skeletal muscles of cold-exposed animals are similar to those observed with endurance training. We hypothesized that increased myoplasmic free [Ca2+] ([Ca2+]i) is important for these adaptations. To test this hypothesis, experiments were performed on flexor digitorum brevis (FDB) muscles, which do not participate in the shivering response, of adult wild-type (WT) and UCP1-ablated (UCP1-KO) mice kept either at room temperature (24°C) or cold-acclimated (4°C) for 4-5 weeks. [Ca2+]i (measured with indo-1) and force were measured under control conditions and during fatigue induced by repeated tetanic stimulation in intact single fibres. The results show no differences between fibres from WT and UCP1-KO mice. However, muscle fibres from cold-acclimated mice showed significant increases in basal [Ca2+]i (?50%), tetanic [Ca2+]i (?40%), and sarcoplasmic reticulum (SR) Ca2+ leak (?fourfold) as compared to fibres from room-temperature mice. Muscles of cold-acclimated mice showed increased expression of peroxisome proliferator-activated receptor-? coactivator-1? (PGC-1?) and increased citrate synthase activity (reflecting increased mitochondrial content). Fibres of cold-acclimated mice were more fatigue resistant with higher tetanic [Ca2+]i and less force loss during fatiguing stimulation. In conclusion, cold exposure induces changes in FDB muscles similar to those observed with endurance training and we propose that increased [Ca2+]i is a key factor underlying these adaptations. PMID:20837639

Bruton, Joseph D; Aydin, Jan; Yamada, Takashi; Shabalina, Irina G; Ivarsson, Niklas; Zhang, Shi-Jin; Wada, Masanobu; Tavi, Pasi; Nedergaard, Jan; Katz, Abram; Westerblad, Håkan

2010-11-01

166

Multi-site control and regulation of mitochondrial energy production  

Microsoft Academic Search

With the extraordinary progress of mitochondrial science and cell biology, novel biochemical pathways have emerged as strategic points of bioenergetic regulation and control. They include mitochondrial fusion, fission and organellar motility along microtubules and microfilaments (mitochondrial dynamics), mitochondrial turnover (biogenesis and degradation), and mitochondrial phospholipids synthesis. Yet, much is still unknown about the mutual interaction between mitochondrial energy state, biogenesis,

G. Benard; N. Bellance; C. Jose; S. Melser; K. Nouette-Gaulain; R. Rossignol

2010-01-01

167

? 2 -Agonists and exercise-induced asthma  

Microsoft Academic Search

?2-Agonists taken immediately before exercise provide significant protection against exercise-induced asthma (EIA) in most patients.\\u000a However, when they are taken daily, there are some negative aspects regarding severity, control, and recovery from EIA. First,\\u000a there is a significant minority (15–20%) of asthmatics whose EIA is not prevented by ?2-agonists, even when inhaled corticosteroids are used concomitantly. Second, with daily use,

Sandra D. Anderson; Corinne Caillaud; John D. Brannan

2006-01-01

168

Exercise-Induced Anaphylaxis and Food-Dependent Exercise-Induced Anaphylaxis  

Microsoft Academic Search

\\u000a Exercise-induced anaphylaxis (EIAn) is characterized by symptoms of anaphylaxis in the setting of significant physical exertion.\\u000a A food-dependent form of exercise-induced ­anaphylaxis also exists, in which symptoms develop only if the patient has eaten\\u000a in the hours immediately preceding exercise. In most patients with the food-dependent form, only a specific food(s) will elicit\\u000a symptoms when combined with exercise, and patients

Anna M. Feldweg; Albert L. Sheffer

169

Mitochondrial biogenesis and healthy aging  

Microsoft Academic Search

Aging is associated with an overall loss of function at the level of the whole organism that has origins in cellular deterioration. Most cellular components, including mitochondria, require continuous recycling and regeneration throughout the lifespan. Mitochondria are particularly susceptive to damage over time as they are the major bioenergetic machinery and source of oxidative stress in cells. Effective control of

Guillermo López-Lluch; Pablo M. Irusta; Placido Navas; Rafael de Cabo

2008-01-01

170

Food-dependent exercise-induced anaphylaxis.  

PubMed

A 58-year-old farmer was admitted to our hospital because of repeated episodes of anaphylaxis. He had experienced 12 episodes of anaphylactic shock over the previous 17 years. These attacks included three episodes of bee sting. In general, the episodes occurred during farm work (exercise) and within two hours of eating cake in the afternoon. Because an immediate skin reaction to wheat flour was highly positive, a diagnosis of wheat allergy was considered. These findings suggested that his illness was consistent with food-dependent exercise-induced anaphylaxis. PMID:1477465

Okazaki, M; Kitani, H; Mifune, T; Mitsunobu, F; Saito, S; Asaumi, N; Tanizaki, Y

1992-08-01

171

The functional interaction of mitochondrial hsp70s with the escort protein zim17 is critical for fe/s biogenesis and substrate interaction at the inner membrane preprotein translocase.  

PubMed

The yeast protein Zim17 belongs to a unique class of co-chaperones that maintain the solubility of Hsp70 proteins in mitochondria and plastids of eukaryotic cells. However, little is known about the functional cooperation between Zim17 and mitochondrial Hsp70 proteins in vivo. To analyze the effects of a loss of Zim17 function in the authentic environment, we introduced novel conditional mutations within the ZIM17 gene of the model organism Saccharomyces cerevisiae that allowed a recovery of temperature-sensitive but respiratory competent zim17 mutant cells. On fermentable growth medium, the mutant cells were prone to acquire respiratory deficits and showed a strong aggregation of the mitochondrial Hsp70 Ssq1 together with a concomitant defect in Fe/S protein biogenesis. In contrast, under respiring conditions, the mitochondrial Hsp70s Ssc1 and Ssq1 exhibited only a partial aggregation. We show that the induction of the zim17 mutant phenotype leads to strong import defects for Ssc1-dependent matrix-targeted precursor proteins that correlate with a significantly reduced binding of newly imported substrate proteins to Ssc1. We conclude that Zim17 is not only required for the maintenance of mtHsp70 solubility but also directly assists the functional interaction of mtHsp70 with substrate proteins in a J-type co-chaperone-dependent manner. PMID:24030826

Lewrenz, Ilka; Rietzschel, Nicole; Guiard, Bernard; Lill, Roland; van der Laan, Martin; Voos, Wolfgang

2013-09-12

172

Intense exercise induces mitochondrial dysfunction in mice brain  

Microsoft Academic Search

There are conflicts between the effects of free radical over-production induced by exercise on neurotrophins and brain oxidative metabolism. The objective of this study was to investigate the effects of intense physical training on brain-derived neurotrophic factor (BDNF) levels, COX activity, and lipoperoxidation levels in mice brain cortex. Twenty-seven adult male CF1 mice were assigned to three groups: control untrained,

Aderbal S. Aguiar Jr; Talita Tuon; Cléber A. Pinho; Luciano A. Silva; Ana C. Andreazza; Flávio Kapczinski; João Quevedo; Emílio L. Streck; Ricardo A. Pinho

2008-01-01

173

Protective Effects of L-Arginine Supplementation Against Exhaustive Exercise-Induced Oxidative Stress in Young Rat Tissues  

Microsoft Academic Search

Recently, we showed that L-arginine (L-Arg) supplementation could attenuate acute exercise- induced oxidative and inflammatory stress in aging rats. In this study, we investigate whether L-Arg supplementation protects cellular oxidative stress, inflammation, or the mitochondrial DNA 4834-bp large deletion (mtDNA4834 deletion) in 14-week-old young rats tissues during exhaustive exercise. Rats were randomly divided into four groups: sedentary control (SC); SC

Chi-Chang Huang; Tien-Jen Lin; Yi-Fa Lu; Chun-Chieh Chen; Chih-Yang Huang; Wan-Teng Lin

174

Schizosaccharomyces pombe homologs of the Saccharomyces cerevisiae mitochondrial proteins Cbp6 and Mss51 function at a post-translational step of respiratory complex biogenesis  

PubMed Central

Complexes III and IV of the mitochondrial respiratory chain contain a few key subunits encoded by the mitochondrial genome. In Saccharomyces cerevisiae, fifteen mRNA-specific translational activators control mitochondrial translation, of which five are conserved in Schizosaccharomyces pombe. These include homologs of Cbp3, Cbp6 and Mss51 that participate in translation and the post-translational steps leading to the assembly of respiratory complexes III and IV. In this study we show that in contrast to budding yeast, Cbp3, Cbp6 and Mss51 from S. pombe are not required for the translation of mitochondrial mRNAs, but fulfill post-translational functions, thus probably accounting for their conservation.

Kuhl, Inge; Fox, Thomas D.; Bonnefoy, Nathalie

2012-01-01

175

Exercise induced compartment syndrome in a professional footballer.  

PubMed

Recurrent pain in the lower leg caused by exercise is a common problem in athletes. The main causes are exercise induced compartment syndrome, periostitis of the tibia, stress fracture, venous diseases, obliterative arterial diseases, and shin splints. Exercise induced compartment syndrome is the least common. A recurrent tightening or tense sensation and aching in anatomically defined compartments is pathognomonic. The symptoms are caused by abnormally high pressure in compartments of the leg during and after exercise. In this report, a case of exercise induced compartment syndrome in a professional footballer is described. PMID:15039267

Cetinus, E; Uzel, M; Bilgiç, E; Karaoguz, A; Herdem, M

2004-04-01

176

Exercise- and training-induced upregulation of skeletal muscle fatty acid oxidation are not solely dependent on mitochondrial machinery and biogenesis.  

PubMed

? Regulation of skeletal muscle fatty acid oxidation (FAO) and adaptation to exercise training have long been thought to depend on delivery of fatty acids (FAs) to muscle, their diffusion into muscle, and muscle mitochondrial content and biochemical machinery. However, FA entry into muscle occurs via a regulatable, protein-mediated mechanism, involving several transport proteins. Among these CD36 is key. Muscle contraction and pharmacological agents induce CD36 to translocate to the cell surface, a response that regulates FA transport, and hence FAO. In exercising CD36 KO mice, exercise duration (-44%), and FA transport (-41%) and oxidation (-37%) are comparably impaired, while carbohydrate metabolism is augmented. In trained CD36 KO mice, training-induced upregulation of FAO is not observed, despite normal training-induced increases in mitochondrial density and enzymes. Transfecting CD36 into sedentary WT muscle (+41%), comparable to training-induced CD36 increases (+44%) in WT muscle, markedly upregulates FAO to rates observed in trained WT mice, but without any changes in mitochondrial density and enzymes. Evidently, in vivo CD36-mediated FA transport is key for muscle fuel selection and training-induced FAO upregulation, independent of mitochondrial adaptations. This CD36 molecular mechanism challenges the view that skeletal muscle FAO is solely regulated by muscle mitochondrial content and machinery. PMID:22890711

Yoshida, Yuko; Jain, Swati S; McFarlan, Jay T; Snook, Laelie A; Chabowski, Adrian; Bonen, Arend

2012-08-13

177

Human mitochondrial ferritin improves respiratory function in yeast mutants deficient in iron-sulfur cluster biogenesis, but is not a functional homologue of yeast frataxin  

PubMed Central

We overexpressed human mitochondrial ferritin in frataxin-deficient yeast cells (?yfh1), but also in another mutant affected in [Fe-S] assembly (?ggc1). Ferritin was correctly processed and expressed in the mitochondria of these cells, but the fraction of total mitochondrial iron bound to ferritin was very low, and most of the iron remained in the form of insoluble particles of ferric phosphate in these mitochondria, as evidenced by gel filtration analysis of the mitochondrial matrix (fast protein liquid chromatography [FPLC]) and by Mössbauer spectroscopy. Mutant cells in which ferritin was overexpressed still accumulated iron in the mitochondria and remained deficient in [Fe-S] assembly, suggesting that human mitochondrial ferritin is not a functional homologue of yeast frataxin. However, the respiratory function was improved in these mutants, which correlates with an improvement of cytochrome and heme synthesis. Overexpression of mitochondrial ferritin in [Fe-S] mutants resulted in the appearance of a small pool of high-spin ferrous iron in the mitochondria, which was probably responsible for the improvement of heme synthesis and of the respiratory function in these mutants.

Sutak, Robert; Seguin, Alexandra; Garcia-Serres, Ricardo; Oddou, Jean-Louis; Dancis, Andrew; Tachezy, Jan; Latour, Jean-Marc; Camadro, Jean-Michel; Lesuisse, Emmanuel

2012-01-01

178

Management of Exercise-Induced Bronchospasm in NCAA Athletic Programs  

Microsoft Academic Search

PARSONS, J. P., V. PESTRITTO, G. PHILLIPS, C. KAEDING, T. M. BEST, G. WADLEY, and J. G. MASTRONARDE. Management of Exercise-Induced Bronchospasm in NCAA Athletic Programs. Med. Sci. Sports Exerc., Vol. 41, No. 4, pp. 737-741, 2009. Purpose: The prevalence of exercise-induced bronchospasm (EIB) is significantly higher in athletes than that in the general population and can result in significant

JONATHAN P. PARSONS; VINCENT PESTRITTO; GARY PHILLIPS; CHRISTOPHER KAEDING; THOMAS M. BEST; GAIL WADLEY; JOHN G. MASTRONARDE

2009-01-01

179

Seasonal Factors Influencing Exercise-Induced Asthma  

PubMed Central

Purpose Exercise-induced bronchoconstriction (EIB) in patients with asthma occurs more frequently in winter than in summer. The concentration of house dust mite (HDM) allergens in beds also shows seasonal variation. This study examined the relationship between seasonal differences in the prevalence of EIB and sensitization to HDMs in patients with asthma. Methods The medical records of 74 young adult male patients with asthma-like symptoms who underwent bronchial challenge with methacholine, 4.5% saline and exercise, and allergen skin prick tests, were reviewed. The subjects were divided into summer (n=27), spring/fall (n=26) and winter (n=21) groups according to the season during which they underwent testing. Results The positive responses to exercise differed according to season (48.1% in summer, 73.1% in spring/fall, and 90.5% in winter; P<0.01). In addition, the prevalence of positive responses to HDM (70.4%, 88.5%, and 95.2%, respectively; P<0.05) and pollen skin tests (37.0%, 19.2%, and 0%, respectively; P<0.01) also showed significant seasonal differences. Severe responses to 4.5% saline showed a similar trend, although it was not statistically significant (44.4%, 50.0%, and 71.4%, respectively; P=0.07). Skin test reactivity to HDMs was significantly related to maximal fall in forced expiratory volume in one second (FEV1) following exercise (r=0.302, P<0.01) and the index of airway hyperresponsiveness (AHR) to 4.5% saline (r=-0.232, P<0.05), but not methacholine (r=-0.125, P>0.05). Conclusions Positive skin test reactions to HDMs and EIB occurred in winter, spring/fall, and summer in decreasing order of frequency. Seasonal variation in the prevalence of EIB may be related to seasonal variation in sensitization to HDMs, accompanied by differences in indirect, but not direct, AHR.

Ki, Won-Joo; Kim, Tae-Ock; Han, Eui-Ryoung; Seo, Il-Kook

2012-01-01

180

Variegation mutants and mechanisms of chloroplast biogenesis  

Microsoft Academic Search

Variegated plants typically have green- and white-sectored leaves. Cells in the green sectors contain normal-appearing chloroplasts, whereas cells in the white sectors lack pig- ments and appear to be blocked at various stages of chlo- roplast biogenesis.Variegations can be caused by mutations in nuclear, chloroplast or mitochondrial genes. In some plants, the green and white sectors have different geno- types,

FEI YU; AIGEN FU; MANEESHA ALURU; YANG XU; HUIYING LIU; XIAYAN LIU; ANDREW FOUDREE; MILLY NAMBOGGA; STEVEN RODERMEL

2007-01-01

181

Current topics in bioenergetics: Structure, biogenesis, and assembly of energy transducing enzyme systems. Volume 15  

SciTech Connect

This book contains 11 chapters. The chapter titles are: Structure of NADH-Ubiquinone Reductase (Complex I); Structure of the Succinate-Ubiquinone Oxidoreductase (Complex II); Structure of Mitochondrial Ubiquinol-Cytochrome-c Redutase (Complex III); Structure of Cytochrome-c Oxidase; Evolution of a Regulatory Enzyme: Cytochrome-c Oxidase (Complex IV); The Assembly of F/sub 1/F/sub 0/-ATPase in Escherichia coli; Biogenesis of Mitochondrial Energy Transducing Complexes; Biogenesis of Mammalian Mitochondria; Structure and Biogenesis of Chloroplast Coupling Factor (CF/sub 0/CF/sub 1/)-ATPase; Mitochondrial Gene Products; and Overview: Bioenergetics between Chemistry, Genetics, and Physics.

Lee, C.P.

1987-01-01

182

Role of Twin Cys-Xaa9-Cys Motif Cysteines in Mitochondrial Import of the Cytochrome c Oxidase Biogenesis Factor Cmc1*  

PubMed Central

The Mia40 import pathway facilitates the import and oxidative folding of cysteine-rich protein substrates into the mitochondrial intermembrane space. Here we describe the in vitro and in organello oxidative folding of Cmc1, a twin CX9C-containing substrate, which contains an unpaired cysteine. In vitro, Cmc1 can be oxidized by the import receptor Mia40 alone when in excess or at a lower rate by only the sulfhydryl oxidase Erv1. However, physiological and efficient Cmc1 oxidation requires Erv1 and Mia40. Cmc1 forms a stable intermediate with Mia40 and is released from this interaction in the presence of Erv1. The three proteins are shown to form a ternary complex in mitochondria. Our results suggest that this mechanism facilitates efficient formation of multiple disulfides and prevents the formation of non-native disulfide bonds.

Bourens, Myriam; Dabir, Deepa V.; Tienson, Heather L.; Sorokina, Irina; Koehler, Carla M.; Barrientos, Antoni

2012-01-01

183

Role of twin Cys-Xaa9-Cys motif cysteines in mitochondrial import of the cytochrome C oxidase biogenesis factor Cmc1.  

PubMed

The Mia40 import pathway facilitates the import and oxidative folding of cysteine-rich protein substrates into the mitochondrial intermembrane space. Here we describe the in vitro and in organello oxidative folding of Cmc1, a twin CX(9)C-containing substrate, which contains an unpaired cysteine. In vitro, Cmc1 can be oxidized by the import receptor Mia40 alone when in excess or at a lower rate by only the sulfhydryl oxidase Erv1. However, physiological and efficient Cmc1 oxidation requires Erv1 and Mia40. Cmc1 forms a stable intermediate with Mia40 and is released from this interaction in the presence of Erv1. The three proteins are shown to form a ternary complex in mitochondria. Our results suggest that this mechanism facilitates efficient formation of multiple disulfides and prevents the formation of non-native disulfide bonds. PMID:22767599

Bourens, Myriam; Dabir, Deepa V; Tienson, Heather L; Sorokina, Irina; Koehler, Carla M; Barrientos, Antoni

2012-07-05

184

Exercise-induced asthma. What family physicians should do.  

PubMed Central

Exercise-induced asthma is described as a transitory increase in airway resistance during or after vigorous exercise. Nearly 90% of patients with chronic asthma and 40% of allergic nonasthmatic patients have the condition. Family physicians should try to educate patients about their asthma and, barring contraindications, encourage them to participate in regular physical activity.

D'Urzo, A.

1995-01-01

185

EXERCISE-INDUCED PULMONARY HEMORRHAGE AFTER RUNNING A MARATHON  

EPA Science Inventory

We report on a healthy 26-year-old male who had an exercise-induced pulmonary hemorrhage (EIPH) within 24 hours of running a marathon. There were no symptoms, abnormalities on exam, or radiographic infiltrates. He routinely participated in bronchoscopy research and the EIPH was e...

186

Exercise-induced knee joint laxity in distance runners  

Microsoft Academic Search

The objectives of this study were to evaluate the effect of exercise on knee joint laxity. If exercise induced laxity is physiological, incorporation of this quality into a ligament replacement material would be indicated. Twenty recreational long distance runners average age 41 (range 24 to 50 yr) were tested before and immediately after 30 minutes of running. Using a computerized

H V Johannsen; T Lind; B W Jakobsen; K Krøner

1989-01-01

187

Exercise-induced orgasm and pleasure among women  

Microsoft Academic Search

Orgasm is typically considered to be a sexual experience. However, orgasms occurring during physical exercise have been occasionally documented. The primary objective of the current study was to understand more about women's experience with exercise-induced orgasm (EIO) including the types of exercise that women have noted have led to EIO and associations with self-reported sexual experiences. A secondary purpose was

Debby Herbenick; J. Dennis Fortenberry

2011-01-01

188

3-D magnetic measurement of exercise-induced MCG.  

PubMed

We carried out a three-dimensional (3-D) vector measurement of exercise-induced magnetocardiograms (MCGs) for normal subjects with a wooden and brass-based bicycle ergometer. MCGs were measured by a 3-D second-order gradiometer connected to 39-channel SQUIDs, which can detect magnetic field components perpendicular to the chest wall (Bz) and tangential to the chest wall (Bx, By) simultaneously. Time-frequency analysis was applied to rest times and exercise-induced MCG data. It was shown that the power spectrum of the ST segment was different between the rest times and exercise-induced MCG. Principal component analysis (PCA) was also applied to the result of time-frequency analysis and the time course of frequency for the ST segment was evaluated quantitatively. It found that dominant frequency of the ST segment in the rest time was ranged 5.5 to 6.5 Hz in all components. And it was clearly shown that the peak frequency of the exercise-induced MCG was shifted to 10.5 Hz compared to that of rest MCG. PMID:16012702

Uchikawa, Y; Kim, B S; Kobayashi, K

2004-11-30

189

Influence of zafirlukast and loratadine on exercise-induced bronchoconstriction  

Microsoft Academic Search

Background: Airway obstruction induced by physical exercise is a common feature in asthma, and conventional treatments do not offer optimal protection. There is thus a need for additional therapies for optimal control of exercise-induced bronchoconstriction (EIB). Objective: The influence of treatment with the antihistamine loratadine and the antileukotriene zafirlukast alone and in combination on EIB was investigated. This combination has

Barbro Dahlén; Annika Roquet; Mark D. Inman; Östen Karlsson; Ian Naya; Gudrun Anstrén; Paul M. O'Byrne; Sven-Erik Dahlén

2002-01-01

190

The biogenesis of rat-liver mitochondrial ATPase. Evidence that the N, N'-dicyclohexyl carbodiimide-binding protein is synthesized outside the mitochondria.  

PubMed

1. Radioactive N,N'-dicyclohexyl carbodiimide (DCCD) is bound as effectively to the N, N'-dicyclohexyl carbodiimide- and oligomycin-sensitive ATPase complex in submitochondrial particles of normal rat liver as to the similar but partially N,N'-dicyclohexyl carbodiimide- and oligomycin-insensitive complex of thiamphenicol-treated rats. The latter complex is deficient in 3 subunits (subunit 6, 7 and 10). 2. Radioactive N,N'-dicyclohexyl carbodiimide is exclusively bound to the subunits present in the bands 8 and 11 of SDS-PAA gels of the purified ATPase complex. These subunits, most likely the dimer and monomer of the N,N'-dicyclohexyl carbodiimide-binding protein, are products of the cytoplasmic protein synthesis. 3. The results together indicate that the N,N'-dicyclohexyl carbodiimide-insensitivity of the ATPase complex formed during in vitro inhibition of mitochondrial protein synthesis, is not caused by a lack of inhibitor binding protein. The same holds for the oligomycin-insensitivity. PMID:6444525

de Jong, L; Holtrop, M; Kroon, A M

1980-02-29

191

Dominance in mitochondrial disorders  

Microsoft Academic Search

Dominant traits are rare in mitochondrial disorders but include important nosological entities such as alterations of organellar biogenesis and abnormalities in the structural integrity of the mitochondrial genome, determined by mutations in genes involved in its maintenance and propagation. Both haplo-insufficiency and ‘gain-of-function’ mechanisms underlie the pathogenesis of these disorders. Impairment in energy supply, abnormal mitochondrial trafficking, increased toxic damage

M. Zeviani; V. Carelli

2005-01-01

192

Mitochondrial autophagy.  

PubMed

Efficient and functional mitochondrial networks are essential for myocardial contraction and cardiomyocyte survival. Mitochondrial autophagy (mitophagy) refers to selective sequestration of mitochondria by autophagosomes, which subsequently deliver them to lysosomes for destruction. This process is essential for myocardial homeostasis and adaptation to stress. Elimination of damaged mitochondria protects against cell death, as well as stimulates mitochondrial biogenesis. Mitophagy is a tightly controlled and highly selective process. It is modulated by mitochondrial fission and fusion proteins, BCL-2 family proteins, and the PINK1/Parkin pathway. Recent studies have provided evidence that miRNAs can regulate mitophagy by controlling the expression of essential proteins involved in the process. Disruption of autophagy leads to rapid accumulation of dysfunctional mitochondria, and diseases associated with impaired autophagy produce severe cardiomyopathies. Thus, autophagy and mitophagy pathways hold promise as new therapeutic targets for clinical cardiac care.??(Circ J?2013; 77: 2449-2454). PMID:23985961

Thomas, Robert L; Gustafsson, Asa B

2013-08-27

193

Biogenesis of telomerase ribonucleoproteins  

PubMed Central

Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation.

Egan, Emily D.; Collins, Kathleen

2012-01-01

194

Exercise-induced second-degree atrioventricular block.  

PubMed

In this report we describe 2 patients with exercise-induced, second-degree atrioventricular (AV) block. Case 1 was a 49-year-old man with normal AV conduction at rest but who developed dyspnea on exertion. Treadmill testing showed an exercise-induced 2:1 AV block. Electrophysiologic study (EPS) demonstrated rate-dependent, presumably intrahissian, AV block. Case 2 was a 31-year-old woman with first-degree AV block and complete right bundle branch block with dyspnea on exertion and occasional syncope. She had twice undergone surgical patch closure of an ostium primum atrial septal defect. Exercise testing induced type II second-degree AV block. Atrial pacing during EPS did not disclose rate-dependent type II AV block, but disopyramide induced second-degree AV block. PMID:9152777

Yuzuki, Y; Horie, M; Makita, T; Watanuki, M; Takahashi, A; Sasayama, S

1997-03-01

195

Exercise-induced vasculitis associated with autoimmune disease.  

PubMed

Exercised-induced vasculitis (EIV) is an underreported and frequently misdiagnosed condition that occurs on the lower extremities shortly after exercise. Most reported cases have presented in healthy-appearing individuals, but some cases have been linked to other disease processes. A case report is presented of recurring EIV in a 65-year-old woman with a history of dermatitis herpetiformis; chronic, mildly elevated liver transaminases of unknown cause; microscopic colitis; celiac disease; multiple miscarriages; and heart block who was found to have autoimmune hepatitis upon workup of her rash. Both EIV and autoimmune hepatitis were misdiagnosed over many years by several clinicians in various specialties. Her family history was remarkable for 2 sisters with systemic lupus erythematosus and similar recurring exercise-induced rashes of the lower extremities, suggesting a familial link for this condition. Clinicians should recognize EIV and consider the possibility that this disorder may be the presenting sign of subclinical connective-tissue diseases. PMID:19681343

Knoell, Keith Allen

2009-06-01

196

Exercise-Induced Anaphylaxis: An Update on Diagnosis and Treatment  

PubMed Central

Exercise-induced anaphylaxis (EIA) and food-dependent, exercise-induced anaphylaxis (FDEIA) are rare but potentially life-threatening clinical syndromes in which association with exercise is crucial. The range of triggering physical activities is broad, including as mild an effort as a stroll. EIA is not fully repeatable (ie, the same exercise may not always result in anaphylaxis in a given patient). In FDEIA, the combined ingestion of sensitizing food and exercise is necessary to precipitate symptoms. Clinical features and management do not differ significantly from other types of anaphylaxis. The pathophysiology of EIA and FDEIA is not fully understood. Different hypotheses concerning the possible influence of exercise on the development of anaphylactic symptoms are taken into consideration. These include increased gastrointestinal permeability, blood flow redistribution, and most likely increased osmolality. This article also describes current diagnostic and therapeutic possibilities, including changes in lifestyle and preventive properties of antiallergic drugs as well as acute treatment of these dangerous syndromes.

Barg, Wojciech; Medrala, Wojciech

2010-01-01

197

The effect of loratadine in exercise-induced asthma  

PubMed Central

Aims: To assess the effect of loratadine in exercise induced asthma. Methods: Randomised, double blind, placebo controlled study of 10 mg oral loratadine, once daily for three days in 11 children. At the end of the treatment period FEV1 was measured, and patients were exercised on a treadmill. FEV1 measurements were repeated at intervals after exercise. Results: Loratadine significantly reduced the decrease in FEV1 after exercise at two, five, 10, 15, and 30 minutes, compared with placebo (p < 0.05). However, the mean decrease in FEV1 at five minutes was more than 15% of baseline in the loratadine group. Conclusions: Loratadine reduces, but does not prevent, exercise induced asthma in children.

Baki, A; Orhan, F

2002-01-01

198

Exercise-Induced Silent Myocardial Ischemia in Master Athletes  

Microsoft Academic Search

High-physical activity levels are associated with reduced risk of symptomatic coronary artery disease (CAD). However, there are a number of reports of exercise-related sudden death and myocardial infarction in aerobically trained athletes. This study compared the prevalence of exercise-induced silent myocardial ischemia on maximum graded exercise tests with tomographic thallium scintigraphy in 70 master male athletes (63 ± 6 years,

Leslie I Katzel; Jerome L Fleg; M. Janette Busby-Whitehead; John D Sorkin; Lewis C Becker; Edward G Lakatta; Andrew P Goldberg

1998-01-01

199

EXERCISE-INDUCED ASTHMA: FRESH INSIGHTS AND AN OVERVIEW  

Microsoft Academic Search

Exercise-induced asthma (EIA) is a common condition affecting 12-15% of the population. Ninety percent of asthmatic individuals and 35-45% of patients with allergic rhinitis are afflicted by EIA, while 3-10% of the general population is also believed to suffer from this condition. EIA is a condition which is more prevalent in strenuous outdoor, cold weather and winter sports. The pathophysiology

R Khajotia

200

Exercise-Induced Deep Vein Thrombosis of the Upper Extremity  

Microsoft Academic Search

Upper-extremity deep venous thrombosis (UEDVT) is an increasingly important clinical problem in children. These events are classified as primary or secondary, with the latter being the most common and usually associated with the presence of a central venous line. Among primary UEDVT, the so-called Paget-Schroetter syndrome, effort-related or exercise-induced upper-extremity thrombotic event represents an extremely rare finding that has never

Leonardo R. Brandão; Suzan Williams; Walter H. A. Kahr; Clodagh Ryan; Michael Temple; Anthony K.C. Chan

2006-01-01

201

Role of leukotrienes in exercise-induced bronchoconstriction  

Microsoft Academic Search

Exercise-induced bronchoconstriction (EIB) refers to acute airflow obstruction that is triggered by a period of physical exertion.\\u000a EIB occurs mainly in individuals with other features of asthma but is especially prominent in a subset of asthmatics with\\u000a pronounced indirect airway hyperresponsiveness. Leukotrienes (LTs) play a critical role in the pathophysiology of EIB. Asthmatics\\u000a who are susceptible to EIB have increased

Teal S. Hallstrand; William R. Henderson Jr

2009-01-01

202

Exercise-induced endotoxemia: the effect of ascorbic acid supplementation  

Microsoft Academic Search

Strenuous, long-duration aerobic exercise results in endotoxemia due to increased plasma levels of lipopolysaccharide (LPS) leading to cytokine release, oxidative stress, and altered gastrointestinal function. However, the effect of short-term strenuous aerobic exercise either with or without antioxidant supplementation on exercise-induced endotoxemia is unknown. A significant increase in the concentration of bacterial LPS (endotoxin) was noted in the venous circulation

Tony Ashton; Ian S Young; Gareth W Davison; Christopher C Rowlands; Jane McEneny; Catherine Van Blerk; Eleri Jones; John R Peters; Simon K Jackson

2003-01-01

203

Exercise induces autophagy in peripheral tissues and in the brain  

PubMed Central

We recently identified physical exercise as a newly defined inducer of autophagy in vivo. Exercise induced autophagy in multiple organs involved in metabolic regulation, such as muscle, liver, pancreas and adipose tissue. To study the physiological role of exercise-induced autophagy, we generated mice with a knock-in nonphosphorylatable mutation in BCL2 (Thr69Ala, Ser70Ala and Ser84Ala) (BCL2 AAA) that are defective in exercise- and starvation-induced autophagy but not in basal autophagy. We found that BCL2 AAA mice could not run on a treadmill as long as wild-type mice, and did not undergo exercise-mediated increases in skeletal glucose muscle uptake. Unlike wild-type mice, the BCL2 AAA mice failed to reverse high-fat diet-induced glucose intolerance after 8 weeks of exercise training, possibly due to defects in signaling pathways that regulate muscle glucose uptake and metabolism during exercise. Together, these findings suggested a hitherto unknown important role of autophagy in mediating exercise-induced metabolic benefits. In the present addendum, we show that treadmill exercise also induces autophagy in the cerebral cortex of adult mice. This observation raises the intriguing question of whether autophagy may in part mediate the beneficial effects of exercise in neurodegeneration, adult neurogenesis and improved cognitive function.

He, Congcong; Sumpter, Jr., Rhea; Levine, Beth

2012-01-01

204

Mitochondrial Turnover in the Heart  

PubMed Central

Mitochondrial quality control is increasingly recognized as an essential element in maintaining optimally functioning tissues. Mitochondrial quality control depends upon a balance between biogenesis and autophagic destruction. Mitochondrial dynamics (fusion and fission) allows for the redistribution of mitochondrial components. We speculate that this permits sorting of highly functional components into one end of a mitochondrion, while damaged components are segregated at the other end, to be jettisoned by asymmetric fission followed by selective mitophagy. Ischemic preconditioning requires autophagy/mitophagy, resulting in selective elimination of damaged mitochondria, leaving behind a population of robust mitochondria with a higher threshold for opening of the mitochondrial permeability transition pore. In this review we will consider the factors that regulate mitochondrial biogenesis and destruction, the machinery involved in both processes, and the biomedical consequences associated with altered mitochondrial turnover.

Gustafsson, Asa B.

2010-01-01

205

Molecular Genetics of Mitochondrial Disorders  

ERIC Educational Resources Information Center

|Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

Wong, Lee-Jun C.

2010-01-01

206

Eucapnic voluntary hyperventilation in diagnosing exercise-induced laryngeal obstructions.  

PubMed

Exercise-induced laryngeal obstructions (EILOs) cause exercise-related respiratory symptoms (ERRS) and are important differential diagnoses to exercise-induced asthma. The diagnostic method for EILOs includes provocation to induce the obstruction followed by a verification of the obstruction and the degree thereof. The objective of the present study was to examine if a eucapnic voluntary hyperventilation (EVH) test could induce laryngeal obstructions laryngoscopically identical in subtypes and development as seen during an exercise test. EVH and exercise testing with continuous laryngoscopy were performed during a screening of two national athletic teams (n = 67). The laryngoscopic recordings were examined for usability, abnormalities and maximal supraglottic and glottic obstruction using two currently available methods (Eilomea and CLE-score). The participants were asked questions on ERRS, and whether the symptoms experienced during each provocation matched those experienced during regular training. A total of 39 completed both tests. There were no significant differences in subtypes and development thereof, the experience of symptoms, and specificity and sensitivity between the methods. Significantly more recordings obtained during the exercise test were usable for evaluation primarily due to resilient mucus on the tip of the fiber-laryngoscope in the EVH test. Only recordings of six athletes from both provocation methods were usable for evaluation using the Eilomea method (high-quality demand). Amongst these, a linear correlation was found for the glottic obstruction. EVH tests can induce EILOs. However, the present test protocol needs adjustments to secure better visualisation of the larynx during provocation. PMID:23732952

Christensen, Pernille M; Rasmussen, Niels

2013-06-04

207

Exercise-induced endocannabinoid signaling is modulated by intensity.  

PubMed

Endocannabinoids (eCB) are endogenous ligands for cannabinoid receptors that are densely expressed in brain networks responsible for reward. Recent work shows that exercise activates the eCB system in humans and other mammals, suggesting eCBs are partly responsible for the reported improvements in mood and affect following aerobic exercise in humans. However, exercise-induced psychological changes reported by runners are known to be dependent on exercise intensity, suggesting that any underlying molecular mechanism should also change with varying levels of exercise intensity. Here, we examine circulating levels of eCBs following aerobic exercise (treadmill running) in recreationally fit human runners at four different intensities. We show that eCB signaling is indeed intensity dependent, with significant changes in circulating eCBs observed following moderate intensities only (very high and very low intensity exercises do not significantly alter circulating eCB levels). Our results are consistent with intensity-dependent psychological state changes with exercise and therefore support the hypothesis that eCB activity is related to neurobiological effects of exercise. Thus, future studies examining the role of exercise-induced eCB signaling on neurobiology or physiology must take exercise intensity into account. PMID:22990628

Raichlen, David A; Foster, Adam D; Seillier, Alexandre; Giuffrida, Andrea; Gerdeman, Gregory L

2012-09-19

208

Exercise-induced bronchoconstriction and atopy in Tunisian athletes  

PubMed Central

Background This study is a cross sectional analysis, aiming to evaluate if atopy is as a risk factor for exercise induced bronchoconstriction (EIB) among Tunisian athletes. Methods Atopy was defined by a skin prick test result and EIB was defined as a decrease of at least 15% in forced expiratory volume in one second (FEV1) after 8-min running at 80–85% HRmaxTheo. The study population was composed of 326 athletes (age: 20.8 ± 2.7 yrs – mean ± SD; 138 women and 188 men) of whom 107 were elite athletes. Results Atopy was found in 26.9% (88/326) of the athletes. Post exercise spirometry revealed the presence of EIB in 9.8% of the athletes including 13% of the elite athletes. Frequency of atopy in athletes with EIB was significantly higher than in athletes without EIB [62.5% vs 23.1%, respectively]. Conclusion This study showed that atopic Tunisian athletes presented a higher risk of developing exercise induced bronchoconstriction than non-atopic athletes.

Sallaoui, Ridha; Chamari, Karim; Mossa, Abbas; Tabka, Zouhair; Chtara, Moktar; Feki, Youssef; Amri, Mohamed

2009-01-01

209

Pharmacological approaches to restore mitochondrial function.  

PubMed

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders but also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson's disease. Numerous pathways maintain and/or restore proper mitochondrial function, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy and the mitochondrial unfolded protein response. New and powerful phenotypic assays in cell-based models as well as multicellular organisms have been developed to explore these different aspects of mitochondrial function. Modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for several diseases, which has spurred active drug discovery efforts in this area. PMID:23666487

Andreux, Pénélope A; Houtkooper, Riekelt H; Auwerx, Johan

2013-05-13

210

Exercise-induced cardiac performance in autoimmune (Type 1) diabetes is associated with a decrease in myocardial diacylglycerol  

PubMed Central

One of the fundamental biochemical defects underlying the complications of diabetic cardiovascular system is elevation of diacylglycerol (DAG) and its effects on protein kinase C (PKC) signaling. It has been noted that exercise training attenuates poor cardiac performance in Type 1 diabetes. However, the role of PKC signaling in exercise-induced alleviation of cardiac abnormalities in diabetes is not clear. We investigated the possibility that exercise training modulates PKC-?II signaling to elicit its beneficial effects on the diabetic heart. bio-breeding diabetic resistant rats, a model reminiscent of Type 1 diabetes in humans, were randomly assigned to four groups: 1) nonexercised nondiabetic (NN); 2) nonexercised diabetic (ND); 3) exercised nondiabetic; and 4) exercised diabetic. Treadmill training was initiated upon the onset of diabetes. At the end of 8 wk, left ventricular (LV) hemodynamic assessment revealed compromised function in ND compared with the NN group. LV myocardial histology revealed increased collagen deposition in ND compared with the NN group, while electron microscopy showed a reduction in the viable mitochondrial fraction. Although the PKC-?II levels and activity were unchanged in the diabetic heart, the DAG levels were increased. With exercise training, the deterioration of LV structure and function in diabetes was attenuated. Notably, improved cardiac performance in training was associated with a decrease in myocardial DAG levels in diabetes. Exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in myocardial DAG levels.

Loganathan, Rajprasad; Novikova, Lesya; Boulatnikov, Igor G.

2012-01-01

211

Biogenesis and Assembly of Eukaryotic Cytochrome c Oxidase Catalytic Core  

PubMed Central

Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin which assembly is intricate and highly regulated. The COX catalytic core is formed by three mitochondrial DNA encoded subunits, Cox1, Cox2 and Cox3, conserved in the bacterial enzyme. Their biogenesis requires the action of messenger-specific and subunit-specific factors which facilitate the synthesis, membrane insertion, maturation or assembly of the core subunits. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to identify these ancillary factors. Here we review the current state of knowledge of the biogenesis and assembly of the eukaryotic COX catalytic core and discuss the degree of conservation of the players and mechanisms operating from yeast to human.

Soto, Ileana C.; Fontanesi, Flavia; Liu, Jingjing; Barrientos, Antoni

2011-01-01

212

Peroxisome Biogenesis and Function  

PubMed Central

Peroxisomes are small and single membrane-delimited organelles that execute numerous metabolic reactions and have pivotal roles in plant growth and development. In recent years, forward and reverse genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to identify many peroxisome proteins and elucidate their functions. This review focuses on the advances in our understanding of peroxisome biogenesis and metabolism, and further explores the contribution of large-scale analysis, such as in sillco predictions and proteomics, in augmenting our knowledge of peroxisome function In Arabidopsis.

Kaur, Navneet; Reumann, Sigrun; Hu, Jianping

2009-01-01

213

Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency  

ERIC Educational Resources Information Center

|Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

2010-01-01

214

Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency  

ERIC Educational Resources Information Center

Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

2010-01-01

215

Suspected exercise-induced seizures in a young dog.  

PubMed

A 12-month-old female neutered crossbreed was referred for investigation of seizure-like episodes occurring only at intense exercise. Thorough medical, neurological and cardiac investigations were performed and excluded the most commonly known causes of seizure-like activity. The dog was fitted with an ambulatory electrocardiography device and underwent another exercise-induced seizure. The electrocardiogram during the episode revealed a sinus tachycardia at approximately 300 beats/minute. A video recording of the episode revealed generalised tonic clonic limb activity with jaw chomping and frothing at the mouth typical of seizure activity. Antiepileptic medications were not prescribed and the owner was advised not to exercise the dog intensely. The dog responded well and did not seizure after 12?months of mild-moderate off-lead exercise. As all the seizures in this case were triggered by intense physical activity, it is suggested that this may be a new form of reflex seizure activity. PMID:23387942

Motta, L; Dutton, E

2013-02-07

216

Moyamoya disease presenting with paroxysmal exercise-induced dyskinesia.  

PubMed

We report a patient with moyamoya disease presenting with paroxysmal exercise-induced dyskinesia (PED). A 31-year-old lathe man developed recurrent attacks of paroxysmal hemichorea. The attacks always affected his left limbs and occurred either after several hours of working or while playing football. The duration of attacks ranged from 30 min to 4h. Attacks were not provoked by sudden movements, consumption of coffee or alcohol, hyperventilation, emotional stress, exposure to cold or passive movement. An MRI of the brain showed no parenchymal lesions. However, (99m)Tc-ethylcysteine dimer SPECT study showed hypoperfusion in the right striatum. Digital subtraction angiography showed stenosis of the right internal carotid and middle cerebral artery with prominent basal collaterals, which was compatible with moyamoya disease. Imaging studies of the cerebral arteries should be done in patients with clinical features of PED in order to detect possible cases of moyamoya disease. PMID:16952479

Lyoo, Chul Hyoung; Kim, Dong Joon; Chang, Hyuk; Lee, Myung Sik

2006-09-06

217

Brief exercise induces an immediate and a delayed leucocytosis.  

PubMed Central

Haematological profiles were measured: (1) before and for 5 h 30 min after 30 min sports (squash, swimming, jogging); and (2) before, during and for 2 h 30 min after 30 min cycle ergometry at workloads which required rates of oxygen consumption that were between 48% and 84% of maximal. In both instances exercise induced an immediate leucocytosis (owing to rises in both neutrophils and lymphocytes) which subsided rapidly at the finish of exercise and was followed by a delayed neutrophilia of greater magnitude which peaked at approximately 3 h after the start of exercise. Changes in plasma catecholamines and cortisol recorded during and after exercise (cycle ergometry only) support the hypothesis that the immediate leucocytosis during brief exercise is attributable to elevated catecholamine levels, whereas the delayed neutrophilia is due to raised cortisol levels.

McCarthy, D A; Grant, M; Marbut, M; Watling, M; Wade, A J; Macdonald, I; Nicholson, S; Melsom, R D; Perry, J D

1991-01-01

218

Unraveling the complexities of SIRT1-mediated mitochondrial regulation in skeletal muscle.  

PubMed

Sirtuin 1 (SIRT1) is a purported central regulator of skeletal muscle mitochondrial biogenesis. Herein, we discuss our recent work using conditional mouse models, which highlight the complexities of SIRT1 biology in vivo, and question the role of SIRT1 in regulating mitochondrial function and mitochondrial adaptations to endurance exercise. Furthermore, we discuss the possible contribution of proposed SIRT1 substrates to muscle mitochondrial biogenesis. PMID:23792490

Philp, Andrew; Schenk, Simon

2013-07-01

219

New Insights into to Pathogenesis of Exercise-induced Bronchoconstriction  

PubMed Central

Purpose of review Exercise-induced bronchoconstriction (EIB) refers to acute airflow obstruction that is triggered by a period of physical exertion. Here we review recent findings about the epidemiology of EIB, immunopathology leading to EIB, and the latest understanding of the pathogenesis of EIB. Recent findings Longitudinal studies demonstrated that airway hyperresponsiveness to exercise or cold air at an early age are among the strongest predictors of persistent asthma. Patients that are susceptible to EIB have epithelial disruption and increased levels of inflammatory eicosanoids such as cysteinyl leukotrienes (CysLT)s. The leukocytes implicated in production of eicosanoids in the airways include both a unique mast cell population as well as eosinophils. A secreted phospholipase A2 (sPLA2) enzyme that serves as a regulator of CysLT formation is present in increased quantities in asthma. Transglutaminase 2 (TGM2) is expressed at increased levels in asthma and serves as a regulator of sPLA2-X. Further, sPLA2-X acts on target cells such as eosinophils to initiate cellular eicosanoid synthesis. Summary Recent studies have advanced our understanding of EIB as a syndrome that is caused by the increased production of inflammatory eicosanoids. The airway epithelium may be an important regulator of the production of inflammatory eicosanoids by leukocytes. Abstract word count: 199

Hallstrand, Teal S.

2012-01-01

220

Diaphragmatic breathing reduces exercise-induced oxidative stress.  

PubMed

Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1?h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals. PMID:19875429

Martarelli, Daniele; Cocchioni, Mario; Scuri, Stefania; Pompei, Pierluigi

2011-02-10

221

Diaphragmatic Breathing Reduces Exercise-Induced Oxidative Stress  

PubMed Central

Diaphragmatic breathing is relaxing and therapeutic, reduces stress, and is a fundamental procedure of Pranayama Yoga, Zen, transcendental meditation and other meditation practices. Analysis of oxidative stress levels in people who meditate indicated that meditation correlates with lower oxidative stress levels, lower cortisol levels and higher melatonin levels. It is known that cortisol inhibits enzymes responsible for the antioxidant activity of cells and that melatonin is a strong antioxidant; therefore, in this study, we investigated the effects of diaphragmatic breathing on exercise-induced oxidative stress and the putative role of cortisol and melatonin hormones in this stress pathway. We monitored 16 athletes during an exhaustive training session. After the exercise, athletes were divided in two equivalent groups of eight subjects. Subjects of the studied group spent 1?h relaxing performing diaphragmatic breathing and concentrating on their breath in a quiet place. The other eight subjects, representing the control group, spent the same time sitting in an equivalent quite place. Results demonstrate that relaxation induced by diaphragmatic breathing increases the antioxidant defense status in athletes after exhaustive exercise. These effects correlate with the concomitant decrease in cortisol and the increase in melatonin. The consequence is a lower level of oxidative stress, which suggests that an appropriate diaphragmatic breathing could protect athletes from long-term adverse effects of free radicals.

Martarelli, Daniele; Cocchioni, Mario; Scuri, Stefania; Pompei, Pierluigi

2011-01-01

222

Resistance to exercise-induced weight loss: compensatory behavioral adaptations.  

PubMed

In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than what the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the subpopulation that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, that is, increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors and to develop strategies to minimize their effect. PMID:23470300

Melanson, Edward L; Keadle, Sarah Kozey; Donnelly, Joseph E; Braun, Barry; King, Neil A

2013-08-01

223

Exercise-induced muscle damage and running economy in humans.  

PubMed

Running economy (RE), defined as the energy demand for a given velocity of submaximal running, has been identified as a critical factor of overall distance running performance. Plyometric and resistance trainings, performed during a relatively short period of time (~15-30 days), have been successfully used to improve RE in trained athletes. However, these exercise types, particularly when they are unaccustomed activities for the individuals, may cause delayed onset muscle soreness, swelling, and reduced muscle strength. Some studies have demonstrated that exercise-induced muscle damage has a negative impact on endurance running performance. Specifically, the muscular damage induced by an acute bout of downhill running has been shown to reduce RE during subsequent moderate and high-intensity exercise (>65% VO?max). However, strength exercise (i.e., jumps, isoinertial and isokinetic eccentric exercises) seems to impair RE only for subsequent high-intensity exercise (~90% VO?max). Finally, a single session of resistance exercise or downhill running (i.e., repeated bout effect) attenuates changes in indirect markers of muscle damage and blunts changes in RE. PMID:23431253

Assumpção, Cláudio de Oliveira; Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Greco, Camila Coelho; Denadai, Benedito Sérgio

2013-02-04

224

In vivo indomethacin reverse exercise-induced immunosuppression in rats.  

PubMed

The effect of oral indomethacin on the immunosuppressive effect of exercise was examined in exercised untrained female Wistar rats immunized with sheep red blood cell (SRBC) antigens. Intensity of the 1 h exercise was controlled by 0-50 kPa air pressure, generated by a compressor located at the bottom of a water tank, during continuous swimming of the rats, previously immunized with SRBC. After 48-72 h, depending on the ip (intraperitoneal) or iv (intravenous) route of SRBC immunization, the exercise suppressed humoral PFC response and augmented phagocytosis of peritoneum macrophages. These effects occurred only when exercise was performed at 48 h after antigen injection. Animals receiving indomethacin, however, did not show any exercise-related suppression of the PFC response. The data suggest a relationship between exercise-induced immunosuppression and possible increased in vivo prostaglandin synthesis during the intense exercise. Overall, exercise-related suppression of humoral PFC response was dependent on the intensity of the exercise, was time specific, and was reversible by pharmacological blockade of the cyclooxygenase pathway of prostaglandin synthesis. PMID:9023588

Asselin, P; Benquet, C; Krzystyniak, K; Brousseau, P; Savard, R; Fournier, M

225

Exercise-induced knee joint laxity in distance runners.  

PubMed Central

The objectives of this study were to evaluate the effect of exercise on knee joint laxity. If exercise induced laxity is physiological, incorporation of this quality into a ligament replacement material would be indicated. Twenty recreational long distance runners average age 41 (range 24 to 50 yr) were tested before and immediately after 30 minutes of running. Using a computerized goniometer type instrument (Acufex KSS), knee flexion, axial tibial rotation and anterior-posterior tibial displacement were simultaneously recorded, while the runners underwent tests of static as well as dynamic knee joint laxity. At 30 degrees of knee flexion, a maximum increase of 16 per cent in mean total anterior-posterior laxity post-exercise was found. At the examination 30 minutes post-exercise, laxity at 30 degrees of knee flexion was still increased. However, laxity at 90 degrees of knee flexion had decreased to pre-exercise levels or below. Anterior tibial displacement, recorded during eccentric quadriceps activity (0 to 90 degrees of knee flexion) with weights attached to the foot, showed a maximum of 18 per cent increase in total anterior-posterior laxity post-exercise. It is suggested that the laxity increase is caused in part by a true ligamentous laxity increase, and in part by a decreased resting tone of the fatigued muscles.

Johannsen, H V; Lind, T; Jakobsen, B W; Kr?ner, K

1989-01-01

226

Genome-wide deletion mutant analysis reveals genes required for respiratory growth, mitochondrial genome maintenance and mitochondrial protein synthesis in Saccharomyces cerevisiae  

Microsoft Academic Search

BACKGROUND: The mitochondrial respiratory chain produces metabolic energy by oxidative phosphorylation. Biogenesis of the respiratory chain requires the coordinated expression of two genomes: the nuclear genome encoding the vast majority of mitochondrial proteins, and the mitochondrial genome encoding a handful of mitochondrial proteins. The understanding of the molecular processes contributing to respiratory chain assembly and maintenance requires the systematic identification

Sandra Merz; Benedikt Westermann

2009-01-01

227

Biogenesis and assembly of eukaryotic cytochrome c oxidase catalytic core.  

PubMed

Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin which assembly is intricate and highly regulated. The COX catalytic core is formed by three mitochondrial DNA encoded subunits, Cox1, Cox2 and Cox3, conserved in the bacterial enzyme. Their biogenesis requires the action of messenger-specific and subunit-specific factors which facilitate the synthesis, membrane insertion, maturation or assembly of the core subunits. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to identify these ancillary factors. Here we review the current state of knowledge of the biogenesis and assembly of the eukaryotic COX catalytic core and discuss the degree of conservation of the players and mechanisms operating from yeast to human. This article is part of a Special Issue entitled: Biogenesis/Assembly of Respiratory Enzyme Complexes. PMID:21958598

Soto, Ileana C; Fontanesi, Flavia; Liu, Jingjing; Barrientos, Antoni

2011-09-16

228

Mitochondrial Therapeutics for Cardioprotection  

PubMed Central

Mitochondria represent approximately one-third of the mass of the heart and play a critical role in maintaining cellular function—however, they are also a potent source of free radicals and pro-apoptotic factors. As such, maintaining mitochondrial homeostasis is essential to cell survival. As the dominant source of ATP, continuous quality control is mandatory to ensure their ongoing optimal function. Mitochondrial quality control is accomplished by the dynamic interplay of fusion, fission, autophagy, and mitochondrial biogenesis. This review examines these processes in the heart and considers their role in the context of ischemia-reperfusion injury. Interventions that modulate mitochondrial turnover, including pharmacologic agents, exercise, and caloric restriction are discussed as a means to improve mitochondrial quality control, ameliorate cardiovascular dysfunction, and enhance longevity.

Carreira, Raquel S.; Lee, Pamela; Gottlieb, Roberta A.

2013-01-01

229

Nutritional modulation of exercise-induced immunodepression in athletes: a systematic review and meta-analysis  

Microsoft Academic Search

Background:Heavy exercise induces marked immunodepression that is multifactorial in origin. Nutrition can modulate normal immune function.Objective:To assess the efficacy of nutritional supplements in exercise-induced immunodepression in athletes.Design:Systematic review.Review methods:Randomised and\\/or controlled trials of athletes undertaking nutritional supplements to minimise the immunodepression after exercise were retrieved. The primary outcome measure was incidence of upper respiratory tract (URT) illness symptoms after exercise,

A Moreira; R A Kekkonen; L Delgado; J Fonseca; R Korpela; T Haahtela

2007-01-01

230

Biogenesis of cytosolic ribosomes requires the essential iron–sulphur protein Rli1p and mitochondria  

Microsoft Academic Search

Mitochondria perform a central function in the biogenesis of cellular iron-sulphur (Fe\\/S) proteins. It is unknown to date why this biosynthetic pathway is indispensable for life, the more so as no essential mitochondrial Fe\\/S pro- teins are known. Here, we show that the soluble ATP- binding cassette (ABC) protein Rli1p carries N-terminal Fe\\/S clusters that require the mitochondrial and cytosolic

Gyula Kispal; Katalin Sipos; Heike Lange; Zsuzsanna Fekete; Tibor Bedekovics; Tamás Janáky; Jochen Bassler; Daili J Aguilar Netz; Janneke Balk; Carmen Rotte; Roland Lill

2005-01-01

231

Effect of exercise intensity on exercise-induced lymphocyte apoptosis.  

PubMed

Because lymphocyte apoptosis is significantly elevated immediately following high-intensity exercise in humans, it seems intuitive that the cell death process must be initiated at some point during the task. This study was designed to determine whether exercise-induced lymphocyte apoptosis occurs at a threshold level of intensity, or exists only following maximal or near-maximal exercise intensities. Fourteen untrained subjects completed a discontinuous, incremental treadmill test to exhaustion (.VO(2max)). Blood for films was sampled before the test, immediately after each work stage, and for 1-h postexercise. Blood smears were stained with May-Grünwald Giemsa and lymphocytes were evaluated for characteristic features of apoptosis. The apoptotic index (AI) during exercise at 38 % .VO(2max) was similar to pre-exercise but significantly elevated at an intensity approximating 61 % .VO(2max) (p < 0.0001). Significant increases in apoptosis were noted with additional elevations in exercise intensity (i.e., 76 %, 89 %, and 100 %, p < 0.0001). Following 20 min of recovery, AI was significantly lower than values obtained immediately postexercise (p < 0.0001). Forty minutes of recovery resulted in a further significant decrease (p < 0.0001), and by 1-h postexercise, AI was similar to pre-exercise values. Results indicate that the exercise intensity threshold for inducing an increase in lymphocyte apoptosis occurs between 40 and 60 % .VO(2max). In addition, since values return to baseline within 1 h following exhaustive exercise, it is unlikely that factors responsible for the apoptotic response in lymphocytes maintain a prolonged presence once exercise has been terminated. PMID:17357968

Navalta, J W; Sedlock, D A; Park, K-S

2007-03-15

232

Circulating androgens in women: exercise-induced changes.  

PubMed

Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance. PMID:21142281

Enea, Carina; Boisseau, Nathalie; Fargeas-Gluck, Marie Agnès; Diaz, Véronique; Dugué, Benoit

2011-01-01

233

Exercise-inducible factors to activate lipolysis in adipocytes.  

PubMed

We examined the effects of exercise training on the levels of lipid droplet (LD)-associated and mitochondria-related proteins in diet-induced obese (DIO) rats. Furthermore, we assessed putative factors induced by exercise to activate lipolysis in differentiated 3T3-L1 adipocytes. DIO Wistar male rats (age 20 wk) were divided into sedentary control (SED, n = 7) and exercise training (EX, n = 7) groups. EX animals were subjected to treadmill running (25 m/min, 1 h/day, 5 days/wk) for 6 wk. Epididymal fat was dissected and used for protein analyses. 3T3-L1 adipocytes were incubated with media containing hydrogen peroxide (H2O2), sodium-lactate, caffeine, AICAR, or SNAP (NO donor) for 6 h, or 1 mM H2O2 for 15 min, followed by incubation with normal media for up to 24 h total. Protein expression levels and lipolytic activities were biochemically assayed. Epididymal fat significantly decreased in EX animals compared with SED animals. Levels of cytochrome c oxidase (COx), perilipin, hormone sensitive lipase (HSL), and adipose triglyceride lipase (ATGL) proteins in epididymal fat pads of EX animals were significantly increased compared with those in SED animals. In 3T3-L1 cells, glycerol or fatty acid release was significantly increased by all treatments. Lactate or SNAP significantly increased PGC-1? expression, and H2O2 significantly increased COx protein levels compared with controls. Expression of perilipin, HSL, ATGL, or comparative gene identification (CGI)-58 was significantly increased by all treatments. By increasing lipolytic activity in adipocytes, the exercise-inducible factors are attractive therapeutic effectors against LD-associated metabolic diseases. PMID:23681914

Hashimoto, Takeshi; Sato, Koji; Iemitsu, Motoyuki

2013-05-16

234

Airway immunopathology of asthma with exercise-induced bronchoconstriction  

PubMed Central

Background: Exercise-induced bronchoconstriction (EIB) is a common cause of symptoms in a subgroup of asthmatic subjects. The pathobiology that makes this group of asthmatic subjects susceptible to bronchoconstriction after a brief period of exercise remains poorly understood. Objective: We sought to determine whether there are differences in lower airway inflammation and production of cytokines and eicosanoids between asthmatic subjects with and without EIB. Methods: Two distinct groups of asthmatic subjects based on a priori definitions were identified, one with moderate-to-severe EIB and the other without significant bronchoconstriction after exercise challenge. Both groups met the definition of asthma on the basis of bronchodilator response, bronchial hyperresponsiveness, or both. A comparative immunopathology study was conducted by using induced sputum to identify differences in lower airway inflammation and production of cytokines and eicosanoids. Results: The groups had similar baseline lung function and bronchodilator response and did not have any asthma exacerbations within the prior year. The concentration of columnar epithelial cells was markedly higher in the group with EIB (1.4 × 105 vs 2.9 × 104 cells/mL, P = .01). The concentration of eosinophils was higher in the group with EIB (3.6 × 104 vs 4.9 × 103 cells/mL P = .04). Cysteinyl leukotrienes (CysLTs; 727.7 vs 151.9 pg/mL, P = .01) and the ratio of CysLTs to prostaglandin E2 (1.85 vs 1.04, P = .002) in the airways were higher in the group with EIB. Conclusion: Injury to the airway epithelium, overexpression of CysLTs, relative underproduction of prostaglandin E2, and greater airway eosinophilia are distinctive immunopathologic features of asthma with EIB. (J Allergy Clin Immunol 2005;116:586-93.)

Hallstrand, Teal S.; Moody, Mark W.; Aitken, Moira L.; Henderson, William R.

2007-01-01

235

Rapid adaptation to eccentric exercise-induced muscle damage.  

PubMed

This study examined eccentric exercise-induced muscle damage and rapid adaptation. Twenty-two male subjects performed 70 eccentric actions with the knee extensors. Group A (n = 11) and group B (n = 11) repeated the same exercise 4 and 13 days after the initial bout, respectively. Criterion measures included muscle soreness, muscle force generation (vertical jump height on a Kistler platform), and plasma levels of creatine kinase (CK), slow-twitch skeletal (cardiac beta-type) myosin heavy chains (MHC), and cardiac troponin I. Subjects were tested pre-exercise and up to day 4 following each bout. The initial exercise resulted in an increase in CK and MHC, a decrement in muscle force, and delayed onset muscle soreness in all participants. CK and MHC release correlated closely (rho = 0.73, p = 0.0001), both did not correlate with the decrement in muscle force generation after exercise. Because cardiac troponin I could not be detected in all samples, which excluded a protein release from the heart (cardiac beta-type MHC), this finding provides evidence for a injury of slow-twitch skeletal muscle fibers in response to eccentric contractions. Repetition of the initial eccentric exercise bout after 13 days (group B) did not cause muscle soreness, a decrement in muscle reaction force with vertical jump or significant changes in plasma MHC and CK concentrations, whereas in case of repetition after 4 days (group A) only the significant increases in CK and MHC were abolished. The decrement in reaction force with vertical jump did not differ significantly from that after the initial exercise session, but perceived muscle soreness was less pronounced.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7591384

Mair, J; Mayr, M; Müller, E; Koller, A; Haid, C; Artner-Dworzak, E; Calzolari, C; Larue, C; Puschendorf, B

1995-08-01

236

17?-estradiol attenuates exercise-induced neutrophil infiltration in men.  

PubMed

17?-estradiol (E2) attenuates exercise-induced muscle damage and inflammation in some models. Eighteen men completed 150 eccentric contractions after random assignment to placebo (Control group) or E2 supplementation (Experimental group). Muscle biopsies and blood samples were collected at baseline, following 8-day supplementation and 3 h and 48 h after exercise. Blood samples were analyzed for sex hormone concentration, creatine kinase (CK) activity and total antioxidant capacity. The mRNA content of genes involved in lipid and cholesterol homeostasis [forkhead box O1 (FOXO1), caveolin 1, and sterol regulatory element binding protein-2 (SREBP2)] and antioxidant defense (SOD1 and -2) were measured by RT-PCR. Immunohistochemistry was used to quantify muscle neutrophil (myeloperoxidase) and macrophage (CD68) content. Serum E2 concentration increased 2.5-fold with supplementation (P < 0.001), attenuating neutrophil infiltration at 3 h (P < 0.05) and 48 h (P < 0.001), and the induction of SOD1 at 48 h (P = 0.02). Macrophage density at 48 h (P < 0.05) and SOD2 mRNA at 3 h (P = 0.01) increased but were not affected by E2. Serum CK activity was higher at 48 h for both groups (P < 0.05). FOXO1, caveolin 1 and SREBP2 expression were 2.8-fold (P < 0.05), 1.4-fold (P < 0.05), and 1.5-fold (P < 0.001) and higher at 3 h after exercise with no effect of E2. This suggests that E2 attenuates neutrophil infiltration; however, the mechanism does not appear to be lesser oxidative stress or membrane damage and may indicate lesser neutrophil/endothelial interaction. PMID:21368271

MacNeil, Lauren G; Baker, Steven K; Stevic, Ivan; Tarnopolsky, Mark A

2011-03-02

237

Salt intake, asthma, and exercise-induced bronchoconstriction: a review.  

PubMed

Despite the heterogeneous treatment options for patients with asthma, there remains a substantial burden of unaddressed disease, even with optimal treatment. Epidemiological studies indicate that patients frequently resort to complimentary and alternative therapies when being treated for asthma and other chronic health conditions. Changes in diet associated with the development of a more affluent lifestyle is one of the environmental factors considered to contribute to the increased prevalence of asthma in the past few decades. Dietary sodium in particular has been considered to be a dietary constituent implicated in this phenomenon. This article reviews the studies conducted that have questioned whether reducing dietary salt intake potentially improves pulmonary function and airway hyper-responsiveness in asthmatics, as well as studies evaluating dietary salt intake on the severity of exercise-induced bronchoconstriction (EIB). The data presented supporting dietary salt restriction for reducing airway hyper-responsiveness in asthmatics is encouraging, though not clinically convincing. Studies conducted previously have been limited for a variety of reasons, including limitations related to the experiment and populations studied. However, in studies that evaluated the severity of EIB in asthmatic individuals and involved altered dietary salt intake, data have been more convincing. A low-sodium diet maintained for 1 to 2 weeks decreases bronchoconstriction in response to exercise in individuals with asthma. There are no data regarding the longer-term effects of a low-sodium diet on either the prevalence or severity of asthma or on EIB. As a low-sodium diet has other beneficial health effects, it can be considered a therapeutic option for adults with asthma, although it should be considered as an adjunctive intervention to supplement optimal pharmacotherapy, and not as an alternative. PMID:20424409

Mickleborough, Timothy D

2010-04-01

238

Iron-sulfur cluster biogenesis and human disease  

PubMed Central

Iron–sulfur (Fe–S) clusters are essential for numerous biological processes, including mitochondrial respiratory chain activity and various other enzymatic and regulatory functions. Human Fe–S cluster assembly proteins are frequently encoded by single genes, and inherited defects in some of these genes cause disease. Recently, the spectrum of diseases attributable to abnormal Fe–S cluster biogenesis has extended beyond Friedreich ataxia to include a sideroblastic anemia with deficiency of glutaredoxin 5 and a myopathy associated with a deficiency of a Fe–S cluster assembly scaffold protein, ISCU. Mutations within other mammalian Fe–S cluster assembly genes could be causative for human diseases that manifest distinctive combinations of tissue-specific impairments. Thus, defects in the iron–sulfur cluster biogenesis pathway could underlie many human diseases.

Rouault, Tracey A.; Tong, Wing Hang

2008-01-01

239

Temporal increase of platelet mitochondrial respiration is negatively associated with clinical outcome in patients with sepsis  

Microsoft Academic Search

INTRODUCTION: Mitochondrial dysfunction has been suggested as a contributing factor to the pathogenesis of sepsis-induced multiple organ failure. Also, restoration of mitochondrial function, known as mitochondrial biogenesis, has been implicated as a key factor for the recovery of organ function in patients with sepsis. Here we investigated temporal changes in platelet mitochondrial respiratory function in patients with sepsis during the

Fredrik Sjövall; Saori Morota; Magnus J Hansson; Hans Friberg; Erich Gnaiger; Eskil Elmér

2010-01-01

240

S-Nitrosylation of Drp1 links excessive mitochondrial fission to neuronal injury in neurodegeneration  

Microsoft Academic Search

Neurons are known to use large amounts of energy for their normal function and activity. In order to meet this demand, mitochondrial fission, fusion, and movement events (mitochondrial dynamics) control mitochondrial morphology, facilitating biogenesis and proper distribution of mitochondria within neurons. In contrast, dysfunction in mitochondrial dynamics results in reduced cell bioenergetics and thus contributes to neuronal injury and death

Tomohiro Nakamura; Piotr Cieplak; Dong-Hyung Cho; Adam Godzik; Stuart A. Lipton

2010-01-01

241

BIOGENESIS OF CHLOROPLAST MEMBRANES  

PubMed Central

This paper describes the morphology and photosynthetic activity of a mutant of Chlamydomonas reinhardi (y-1) which is unable to synthesize chlorophyll in the dark. When grown heterotrophically in the light, the mutant is indistinguishable from the wild type Chlamydomonas. When grown in the dark, chlorophyll is diluted through cell division and the photosynthetic activity (oxygen evolution, Hill reaction, and photoreduction of NADP) decays at a rate equal to or faster than that of chlorophyll dilution. However, soluble enzymes associated with the photosynthetic process (alkaline FDPase, NADP-linked G-3-P dehydrogenase, RuDP carboxylase), as well as cytochrome f and ferredoxin, continue to be present in relatively high concentrations. The enzymes involved in the synthesis of the characteristic lipids of the chloroplast (including mono- and digalactoside glycerides, phosphatidyl glycerol, and sulfolipid) are still detectable in dark-grown cells. Such cells accumulate large amounts of starch granules in their plastids. On onset of illumination, dark-grown cells synthesize chlorophyll rapidly, utilizing their starch reserve in the process. At the morphological level, it was observed that during growth in the dark the chloroplast lamellar system is gradually disorganized and drastically decreased in extent, while other subchloroplast components are either unaffected (pyrenoid and its tubular system, matrix) or much less affected (eyespot, ribosomes). It is concluded that the dark-grown mutant possesses a partially differentiated plastid and the enzymic apparatus necessary for the synthesis of the chloroplast membranes (discs). The advantage provided by such a system for the study of the biogenesis of the chloroplast photosynthetic membranes is discussed.

Ohad, I.; Siekevitz, P.; Palade, G. E.

1967-01-01

242

Mitochondrial signaling: forwards, backwards, and in between.  

PubMed

Mitochondria are semiautonomous organelles that are a defining characteristic of almost all eukaryotic cells. They are vital for energy production, but increasing evidence shows that they play important roles in a wide range of cellular signaling and homeostasis. Our understanding of nuclear control of mitochondrial function has expanded over the past half century with the discovery of multiple transcription factors and cofactors governing mitochondrial biogenesis. More recently, nuclear changes in response to mitochondrial messaging have led to characterization of retrograde mitochondrial signaling, in which mitochondria have the ability to alter nuclear gene expression. Mitochondria are also integral to other components of stress response or quality control including ROS signaling, unfolded protein response, mitochondrial autophagy, and biogenesis. These avenues of mitochondrial signaling are discussed in this review. PMID:23819011

Whelan, Sean P; Zuckerbraun, Brian S

2013-05-29

243

Oxidants, Antioxidants, and the Beneficial Roles of Exercise-Induced Production of Reactive Species  

PubMed Central

This review offers an overview of the influence of reactive species produced during exercise and their effect on exercise adaptation. Reactive species and free radicals are unstable molecules that oxidize other molecules in order to become stable. Although they play important roles in our body, they can also lead to oxidative stress impairing diverse cellular functions. During exercise, reactive species can be produced mainly, but not exclusively, by the following mechanisms: electron leak at the mitochondrial electron transport chain, ischemia/reperfusion and activation of endothelial xanthine oxidase, inflammatory response, and autooxidation of catecholamines. Chronic exercise also leads to the upregulation of the body's antioxidant defence mechanism, which helps minimize the oxidative stress that may occur after an acute bout of exercise. Recent studies show a beneficial role of the reactive species, produced during a bout of exercise, that lead to important training adaptations: angiogenesis, mitochondria biogenesis, and muscle hypertrophy. The adaptations occur depending on the mechanic, and consequently biochemical, stimulus within the muscle. This is a new area of study that promises important findings in the sphere of molecular and cellular mechanisms involved in the relationship between oxidative stress and exercise.

Gomes, Elisa Couto; Silva, Albena Nunes; de Oliveira, Marta Rubino

2012-01-01

244

Variegation mutants and mechanisms of chloroplast biogenesis.  

PubMed

Variegated plants typically have green- and white-sectored leaves. Cells in the green sectors contain normal-appearing chloroplasts, whereas cells in the white sectors lack pigments and appear to be blocked at various stages of chloroplast biogenesis. Variegations can be caused by mutations in nuclear, chloroplast or mitochondrial genes. In some plants, the green and white sectors have different genotypes, but in others they have the same (mutant) genotype. One advantage of variegations is that they provide a means of studying genes for proteins that are important for chloroplast development, but for which mutant analysis is difficult, either because mutations in a gene of interest are lethal or because they do not show a readily distinguishable phenotype. This paper focuses on Arabidopsis variegations, for which the most information is available at the molecular level. Perhaps the most interesting of these are variegations caused by defective nuclear gene products in which the cells of the mutant have a uniform genotype. Two questions are of paramount interest: (1) What is the gene product and how does it function in chloroplast biogenesis? (2) What is the mechanism of variegation and why do green sectors arise in plants with a uniform (mutant) genotype? Two paradigms of variegation mechanism are described: immutans (im) and variegated2 (var2). Both mechanisms emphasize compensating activities and the notion of plastid autonomy, but redundant gene products are proposed to play a role in var2, but not in im. It is hypothesized that threshold levels of certain activities are necessary for normal chloroplast development. PMID:17263779

Yu, Fei; Fu, Aigen; Aluru, Maneesha; Park, Sungsoon; Xu, Yang; Liu, Huiying; Liu, Xiayan; Foudree, Andrew; Nambogga, Milly; Rodermel, Steven

2007-03-01

245

325 Exercise-induced Airway Obstruction and Vitamin D Deficiency  

PubMed Central

Background Exercise-induced (EI) symptoms may be associated with bronchospasm (EI-B), or laryngospasm, that is a paradoxical VC adduction (VCD) mimicking asthma. We previously found that vitamin D deficiency (Ddef) favours the occurrence of VCD during hyperventilation test (HV), particularly in hypocapnic conditions. We evaluated the occurrence of EI-B and EI-VCD during HV in relationship with Ddef, in 37 non smoking young athletes (24 males, 13 females, age: 13–25 years). Methods Each subject underwent HV (5 runs of one minute) either in isocapnia (HViso, obtained breathing CO2 enriched air) or in hypocapnia (HVhypo, obtained breathing normal air) in randomized order, one week apart. Exhaled CO2 pressure was controlled breath by breath by a capnograph. A 10% decrease in FEV1 was used as EI-B marker, a 25% decrease in MIF50 as EI-VCD marker. Results Sixteen subjects (43%) were atopic, 6 (16%) reported past diagnosis of asthma. No subject was assuming drugs or had suffered from respiratory infections in the last month. All subjects had normal lung function tests. With HViso 10 subjects had EI-B and 12 had EI-VCD. With HVhypo 8 subjects had EI-B and 15 EI-VCD. Eighteen subiects (49%) had Ddef (serum 25-hydroxycholecalcipherol < 25 ng/mL). Serum levels of vitamin D were significantly lower in athletes with than in those without EI-VCD, either with HViso (19.1 ± 1.8 vs 25.7 ± 1.5 ng/mL; P = 0.013) or with HVhypo (20.2 ± 1.9 vs 26.2 ± 1.8 ng/mL; P = 0.029). No influence of vitamin D on EI-B could be demonstrated. Vitamin D levels were significantly related to the decrease in MIF50 (as % of baseline) during the test (HViso: r = 0.41; P < 0.015 and HVipo: r = 0.42; P = 0.017). Conclusions Our young athletes had a high prevalence of paradoxical vocal cord adduction during HV, which was strongly associated to Ddef. The high prevalence of Ddef was expected, since the study was conducted during winter in a town located beyond 45° latitude. Vitamin D deficiency may favour laryngospasm by decreasing calcium availability, ATP production and Ca-ATPase pump activity in the striate muscle cell, with consequent tetanic contraction and delayed relaxation. The fact that alkalosis worsens hypocalcemia accounts for the higher prevalence of laryngospasm observed during HVhypo.

Varenni, Davide; Heffler, Enrico; Papurello, Martina; Culla, Beatrice; Brussino, Luisa; Guida, Giuseppe; Bucca, Caterina; Masoero, Monica

2012-01-01

246

Mitochondrial dysfunction during sepsis.  

PubMed

Sepsis and multiple organ failure remain leading causes of death in intensive care patients. Recent advances in our understanding of the pathophysiology of these syndromes include a likely prominent role for mitochondria. Patient studies have shown that the degree of mitochondrial dysfunction is related to the eventual outcome. Associated mechanisms include damage to mitochondria or inhibition of the electron transport chain enzymes by nitric oxide and other reactive oxygen species (the effects of which are amplified by co-existing tissue hypoxia), hormonal influences that decrease mitochondrial activity, and downregulation of mitochondrial protein expression. Notably, despite these findings, there is minimal cell death seen in most affected organs, and these organs generally regain reasonably normal function should the patient survive. It is thus plausible that multiple organ failure following sepsis may actually represent an adaptive state whereby the organs temporarily 'shut down' their normal metabolic functions in order to protect themselves from an overwhelming and prolonged insult. A decrease in energy supply due to mitochondrial inhibition or injury may trigger this hibernation/estivation-like state. Likewise, organ recovery may depend on restoration of normal mitochondrial respiration. Data from animal studies show histological recovery of mitochondria after a septic insult that precedes clinical improvement. Stimulation of mitochondrial biogenesis could offer a new therapeutic approach for patients in multi-organ failure. This review will cover basic aspects of mitochondrial function, mechanisms of mitochondrial dysfunction in sepsis, and approaches to prevent, mitigate or speed recovery from mitochondrial injury. PMID:20509844

Azevedo, Luciano Cesar Pontes

2010-09-01

247

Reciprocal ST-segment depression associated with exercise-induced ST-segment elevation indicates residual viability after myocardial infarction  

Microsoft Academic Search

OBJECTIVESWe evaluated the clinical significance of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability within the infarcted area.BACKGROUNDAlthough the relation between residual viability and exercise-induced ST-segment elevation has been described, there are no reports focusing on the relation between myocardial viability and reciprocal ST-segment depression associated with exercise-induced ST-segment elevation.METHODSWe evaluated regional blood flow and glucose

Akira Nakano; Jong-Dae Lee; Hiromasa Shimizu; Tatsuro Tsuchida; Yoshiharu Yonekura; Yasushi Ishii; Takanori Ueda

1999-01-01

248

Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina  

Microsoft Academic Search

The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation

Y. Matsuda; M. Ozaki; H. Ogawa; H. Naito; F. Yoshino; K. Katayama; T. Fujii; M. Matsuzaki; R. Kusukawa

1983-01-01

249

The essential role of mitochondria in the biogenesis of cellular iron-sulfur proteins.  

PubMed

Iron-sulfur (Fe/S) proteins play an important role in electron transfer processes and in various enzymatic reactions. In eukaryotic cells, known Fe/S proteins are localised in mitochondria, the cytosol and the nucleus. The biogenesis of these proteins has only recently become the focus of investigations. Mitochondria are the major site of Fe/S cluster biosynthesis in the cell. The organelles contain an Fe/S cluster biosynthesis apparatus that resembles that of prokaryotic cells. This apparatus consists of some ten proteins including a cysteine desulfurase producing elemental sulfur for biogenesis, a ferredoxin involved in reduction, and two chaperones. The mitochondrial Fe/S cluster synthesis apparatus not only assembles mitochondrial Fe/S proteins, but also initiates formation of extra-mitochondrial Fe/S proteins. This involves the export of sulfur and possibly iron from mitochondria to the cytosol, a reaction performed by the ABC transporter Atm1p of the mitochondrial inner membrane. A possible substrate of Atm1p is an Fe/S cluster that may be stabilised for transport. Constituents of the cytosol involved in the incorporation of the Fe/S cluster into apoproteins have not been described yet. Many of the mitochondrial proteins involved in Fe/S cluster formation are essential, illustrating the central importance of Fe/S proteins for life. Defects in Fe/S protein biogenesis are associated with the abnormal accumulation of iron within mitochondria and are the cause of an iron storage disease. PMID:10595578

Lill, R; Diekert, K; Kaut, A; Lange, H; Pelzer, W; Prohl, C; Kispal, G

1999-10-01

250

Wheat-dependent, Exercise-induced Anaphylaxis: A Successful Case of Prevention with Ketotifen  

PubMed Central

Food-dependent, exercise-induced anaphylaxis (FDEIA) is the triggering of anaphylaxis after ingestion of certain foods when followed by physical exercise. Symptoms vary from the typical generalized urticaria to severe allergic reactions. We report the case of a 20-year-old woman who had a 7-year history of recurrent wheals and dyspnea after ingesting several kinds of food (wheat, pork, and beef) along with physical exercise. Based on a provocation test, she was diagnosed with wheat-dependent, exercise-induced anaphylaxis. She was instructed to take 2 mg of ketotifen 2 hours before ingestion of wheat to prevent the symptoms, and subsequently the provocation test did not elicit wheals. We therefore prescribed ketotifen (1 mg twice a day). She has not had recurrent wheals or dyspnea for 6 months. We herein report an interesting case of wheat-dependent, exercise-induced anaphylaxis with successful prevention by ketotifen.

Choi, Ji Hoon; Lee, Hee Bong; Ahn, In Su; Lee, Cheol Heon

2009-01-01

251

[Bronchial hyperresponsiveness and factors of bronchial inflammation under the exercise-induced asthma in schoolchildren].  

PubMed

88 schoolchildren with bronchial asthma were observed at the department of pulmonary disease and allergology of the Chernivtsi regional children clinical hospital. The study showed that the content of aldehyde- and ketoderivatives of 2,4-dinitrophenylhydrazones of neutral character in the expired air condensate (AKDNPH) was presumably higher in patients with the exercise-induced bronchial asthma thus indicating the more significant activity of the inflammatory process in bronchi under the studied phenotype of the disease. Non-specific bronchial hyperresponsiveness was presumably higher in children suffering exercise-induced bronchial asthma due to bronchial hyperresponsiveness as well as hyperreactivity when compared with the patients having activity independent asthma attacks. The factor of bronchial spasm was significantly associated with the content of AKDNPH of the basic character and nitric oxide metabolites in the expired air condensate in the patients with the exercise-induced bronchial asthma. PMID:23356141

Ivanova, L A

252

mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis.  

PubMed

The coding regions of many mitochondrial genes in plants are interrupted by intervening sequences that are classified as group II introns. Their splicing is essential for the expression of the genes they interrupt and hence for respiratory function, and is facilitated by various protein cofactors. Despite the importance of these cofactors, only a few of them have been characterized. CRS1-YhbY domain (CRM) is a recently recognized RNA-binding domain that is present in several characterized splicing factors in plant chloroplasts. The Arabidopsis genome encodes 16 CRM proteins, but these are largely uncharacterized. Here, we analyzed the intracellular location of one of these hypothetical proteins in Arabidopsis, mitochondrial CAF-like splicing factor 1 (mCSF1; At4 g31010), and analyzed the growth phenotypes and organellar activities associated with mcsf1 mutants in plants. Our data indicated that mCSF1 resides within mitochondria and its functions are essential during embryogenesis. Mutant plants with reduced mCSF1 displayed inhibited germination and retarded growth phenotypes that were tightly associated with reduced complex I and IV activities. Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria. PMID:23646912

Zmudjak, Michal; Colas des Francs-Small, Catherine; Keren, Ido; Shaya, Felix; Belausov, Eduard; Small, Ian; Ostersetzer-Biran, Oren

2013-05-07

253

HSC20 interacts with frataxin and is involved in iron-sulfur cluster biogenesis and iron homeostasis  

PubMed Central

Friedreich's ataxia is a neurodegenerative disorder caused by mutations in the frataxin gene that produces a predominantly mitochondrial protein whose primary function appears to be mitochondrial iron–sulfur cluster (ISC) biosynthesis. Previously we demonstrated that frataxin interacts with multiple components of the mammalian ISC assembly machinery. Here we demonstrate that frataxin interacts with the mammalian mitochondrial chaperone HSC20. We show that this interaction is iron-dependent. We also show that like frataxin, HSC20 interacts with multiple proteins involved in ISC biogenesis including the ISCU/Nfs1 ISC biogenesis complex and the GRP75 ISC chaperone. Furthermore, knockdown of HSC20 caused functional defects in activity of mitochondrial ISC-containing enzymes and also defects in ISC protein expression. Alterations up or down of frataxin expression caused compensatory changes in HSC20 expression inversely, as expected of two cooperating proteins operating in the same pathway and suggesting a potential therapeutic strategy for the disease. Knockdown of HSC20 altered cytosolic and mitochondrial iron pools and increased the expression of transferrin receptor 1 and iron regulatory protein 2 consistent with decreased iron bioavailability. These results indicate that HSC20 interacts with frataxin structurally and functionally and is important for ISC biogenesis and iron homeostasis in mammals. Furthermore, they suggest that HSC20 may act late in the ISC pathway as a chaperone in ISC delivery to apoproteins and that HSC20 should be included in multi-protein complex studies of mammalian ISC biogenesis.

Shan, Yuxi; Cortopassi, Gino

2012-01-01

254

Exercise-induced acute renal failure associated with renal hypouricaemia: results of a questionnaire-based survey in Japan  

Microsoft Academic Search

Background. A retrospective investigation was con- ducted to define the clinical features of exercise- induced acute renal failure (ARF) associated with renal hypouricaemia with the aim of clarifying further the clinical features of the disease entity. Methods. A questionnaire was mailed to 43 institu- tions in Japan that had experienced case(s) of exercise- induced ARF associated with renal hypouricaemia. Fifty-four

Toshiyuki Ohta; Takashi Sakano; Takashi Igarashi; Noritomo Itami; Takahiko Ogawa

2004-01-01

255

Mitochondrial dysfunction in heart failure.  

PubMed

Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF, several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cyclic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction. PMID:22948484

Rosca, Mariana G; Hoppel, Charles L

2013-09-01

256

Peroxisome biogenesis in Saccharomyces cerevisiae  

Microsoft Academic Search

The observation that peroxisomes ofSaccharomyces cerevisiae can be induced by oleic acid has opened the possibility to investigate the biogenesis of these organelles in a biochemically and genetically well characterized organism. Only few enzymes have been identified as peroxisomal proteins inSaccharomyces cerevisiae so far; the three enzymes involved in ß-oxidation of fatty acids, enzymes of the glyoxylate cycle, catalase A

Wolf-H. Kunau; Andreas Hartig

1992-01-01

257

Coronary arteriography and left ventriculography during spontaneous and exercise-induced ST segment elevation in patients with variant angina  

SciTech Connect

The present study is an angiographic demonstration of coronary artery spasm during both spontaneous and exercise-induced angina in three patients with variant angina. In each case, clinical, ECG, coronary angiographic, and left ventriculographic observations were made at rest, during spontaneous angina, and during exercise-induced angina. The character of chest pain was similar during spontaneous and exercise-induced episodes. ST segment elevation was present in the anterior ECG leads during both episodes. The left anterior descending coronary artery became partially or totally obstructed during both types of attacks. When coronary spasm was demonstrated during both types of attacks, left ventriculography disclosed akinetic or dyskinetic wall motion in the area supplied by the involved artery. In those patients with reproducible exercise-induced ST segment elevation and chest pain, thallium-201 scintigraphy showed areas of reversible anteroseptal hypoperfusion. Thus in selected patients exercise-induced attacks of angina were similar to spontaneous episodes.

Matsuda, Y.; Ozaki, M.; Ogawa, H.; Naito, H.; Yoshino, F.; Katayama, K.; Fujii, T.; Matsuzaki, M.; Kusukawa, R.

1983-09-01

258

High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial  

Technology Transfer Automated Retrieval System (TEKTRAN)

Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metaboli...

259

Gender differences in exerciseinduced intravascular haemolysis during race training in thoroughbred horses  

Microsoft Academic Search

Exercise-induced intravascular haemolysis and “sport anemia” are widely reported in human sports medicine. It has been recognized also in horses, however, the clinical importance and the onset of this condition seem different than in human. In this study we investigated the episodes of intravascular haemolysis, indicated by the increase in plasma haemoglobin and the decrease in serum haptoglobin levels, after

Anna Cywinska; Ewa Szarska; Agnieszka Kowalska; Piotr Ostaszewski; Antoni Schollenberger

2011-01-01

260

The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.  

ERIC Educational Resources Information Center

Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

2001-01-01

261

Review of Exercise-Induced Muscle Injury: Relevance for Athletic Populations  

Microsoft Academic Search

Exercise-induced skeletal muscle injury is well understood as the product of unfamiliar or strenuous physical activity. Eccentric or lengthening actions are primarily responsible for inducing injury, which subsequently leads to a variety of signs and symptoms. Although significant research supports this finding, most observations are specific to untrained individuals. In addition, many protocols designed both to induce muscle injury and

Michael J. Falvo; Richard J. Bloomer

2006-01-01

262

Influence of artistic gymnastics on iron nutritional status and exercise-induced hemolysis in female athletes.  

PubMed

This study evaluates the relationship between body iron losses and gains in artistic gymnastics female athletes. It shows that despite the low iron intake and exercise-induced hemolysis, iron deficiency or iron-deficiency anemia does not occur, but partial changes in the hematological profile do. The hypothesis that gymnasts' nutritional behavior contributes to anemia, which may be aggravated by exercise-induced hemolysis, led to this cross-sectional study, conducted with 43 female artistic gymnasts 6-16 yr old. The control group was formed by 40 nontraining girls, paired by age. Hemogram, serum iron, ferritin, soluble transferrin receptor, haptoglobin, total and fractional bilirubin, Type I urine, and parasitologic and occult fecal blood tests were evaluated. The athletes presented mean hematimetric and serum iron values (p = .020) higher than those of the control group. The bilirubin result discarded any hemolytic alteration in both groups. The haptoglobin results were lower in the athlete group (p = .002), confirming the incidence of exercise-induced hemolysis. Both groups presented low iron intake. The results suggest that artistic gymnastics practice leads to exercise-induced hemolysis and partially changes the hematological profile, although not causing iron deficiency or iron-deficiency anemia, even in the presence of low iron intake. PMID:22645172

Sureira, Thaiz Mattos; Amancio, Olga Silverio; Pellegrini Braga, Josefina Aparecida

2012-05-10

263

Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography  

Microsoft Academic Search

Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and

C. Kurata; K. Sakata; T. Taguchi; A. Kobayashi; N. Yamazaki

1990-01-01

264

The Prevalence of Exercise-Induced Bronchospasm in Soccer Player Children, Ages 7 to 16 Years  

Microsoft Academic Search

This study represents an attempt to determine the prevalence of exercise-induced bronchospasm among soccer player children. A total of 234 soccer player boys of all soccer schools from Shahr-Rey enrolled in this study. They did not have any history of a recent or chronic respiratory tract disease, a history of allergic diseases, and history of bronchodilator drugs consumption during the

Vahid Ziaee; Azizollah Yousefi; Massoud Movahedi; Farhad Mehrkhani; Rohollah Noorian

265

The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage.  

ERIC Educational Resources Information Center

|Investigated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in men randomly administered Cr or placebo. Results indicated that 5 days of Cr supplementation did not reduce indirect makers of muscle damage or enhance recovery from high-force eccentric exercise.…

Rawson, Eric S.; Gunn, Bridget; Clarkson, Priscilla M.

2001-01-01

266

Dietary salt alters pulmonary function during exercise in exercise-induced asthmatics  

Microsoft Academic Search

Epidemiological and experimental studies have suggested that dietary salt may play a role in airway responsiveness. We have previously shown that a low salt diet improves and a high salt diet exacerbates post-exercise pulmonary function in individuals with exercise-induced asthma. The aim of this study was to determine the influence of both elevated and restricted salt diets on pulmonary function

Timothy D. Mickleborough; Robert W. Gotshall; Loren Cordain; Martin Lindley

2001-01-01

267

Exercise-induced blood flow in relation to muscle relaxation period  

Microsoft Academic Search

BACKGROUND: Dynamic exercise is characterized by relaxation periods between contractions. The relaxation period should be considered as a causal factor for determining the magnitude of blood flow during dynamic exercise. The purpose of this study was to investigate the effect of muscle relaxation periods determined by the response of each subject on the exercise-induced blood flow response. METHODS: Seven healthy

Fumiko Ohmori; Shizuyo Shimizu; Atsuko Kagaya

2007-01-01

268

Foot Cooling Reduces Exercise-Induced Hyperthermia in Men with Spinal Cord Injury  

Microsoft Academic Search

HAGOBIAN, T. A., K. A. JACOBS, B. J. KIRATLI, and A. L. FRIEDLANDER. Foot Cooling Reduces Exercise-Induced Hyperthermia in Men with Spinal Cord Injury. Med. Sci. Sports Exerc., Vol. 36, No. 3, pp. 411- 417, 2004. The number of individuals with spinal cord injury (SCI) participating in sports at recreational and elite levels is on the rise. However, loss of

TODD A. HAGOBIAN; KEVIN A. JACOBS; B. JENNY KIRATLI; ANNE L. FRIEDLANDER

2004-01-01

269

Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss in Overweight and Obese Adults  

Microsoft Academic Search

This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercise-induced weight loss. Participants (n ¼ 132 with 107 completers) were randomly assigned to receive a beverage containing ;625 mg of catechins with 39 mg caffeine or a control beverage (39 mg caffeine, no catechins) for 12

Kevin C. Maki; Matthew S. Reeves; Mildred Farmer; Koichi Yasunaga; Noboru Matsuo; Yoshihisa Katsuragi; Masanori Komikado; Ichiro Tokimitsu; Donna Wilder; Franz Jones; Jeffrey B. Blumberg; Yolanda Cartwright

2008-01-01

270

Role of Leukotriene Receptor Antagonists in the Treatment of Exercise-Induced Bronchoconstriction: A Review  

PubMed Central

Asthma is a very common disorder that still causes significant morbidity and mortality. A high percentage of individuals with asthma also experience exercise-induced bronchoconstriction (EIB). This article reviews the current literature and updates the reader on the safety, efficacy, and clinical applications of leukotriene modifiers in the treatment of EIB.

2005-01-01

271

Prevalence and prognostic significance of exercise-induced supraventricular tachycardia in apparently healthy volunteers.  

PubMed

The prevalence, characteristics, and prognostic significance of supraventricular tachycardia (SVT) occurring during maximal treadmill exercise testing were examined in 843 male and 540 female asymptomatic volunteers aged 20 to 94 years from the Baltimore Longitudinal Study of Aging who underwent exercise testing a mean of 2.3 times between 1977 and 1991. Exercise-induced SVT occurred during at least 1 test in 51 men (6.0%) and 34 women (6.3%), p = NS for gender. The 85 subjects with exercise-induced SVT were significantly older than the 1,298 free from this arrhythmia (66.0 +/- 13.5 vs 49.7 +/- 18.0 years, respectively, p < 0.001). The prevalence of SVT increased with age in men (p < 0.001) but not in women. Ninety-eight percent of the 141 discrete episodes of exercise-induced SVT were paroxysmal SVT, with heart rates varying from 105 to 290 beats/min (mean 186.3 +/- 43.3); only 16% were > 10 beats in duration and only 4% of subjects were symptomatic. Nearly half (44%) of SVT episodes occurred at peak effort. Coronary risk factors, echocardiographic left atrial size (3.3 +/- 6.7 vs 3.3 +/- 0.6 cm), and the prevalence of exercise-induced ischemic ST-segment depression (11% vs 13%) were similar in 85 subjects with SVT and 170 control subjects matched for age and sex.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7717280

Maurer, M S; Shefrin, E A; Fleg, J L

1995-04-15

272

Prevalence and prognostic significance of exercise-induced supraventricular tachycardia in apparently healthy volunteers  

Microsoft Academic Search

The prevalence, characteristics, and prognostic significance of supraventricular tachycardia (SVT) occurring during maximal treadmill exercise testing were examined in 843 male and 540 female asymptomatic volunteers aged 20 to 94 years from the Baltimore Longitudinal Study of Aging who underwent exercise testing a mean or 2.3 times between 1977 and 1991. Exercise-induced SVT occurred during at least 1 test in

Mathew S. Maurer; Elliot A. Shefrin; Jerome L. Fleg

1995-01-01

273

Exercise-induced cardioprotection: a role for eNOS uncoupling and NO metabolites.  

PubMed

Exercise is an efficient strategy for myocardial protection against ischemia-reperfusion (IR) injury. Although endothelial nitric oxide synthase (eNOS) is phosphorylated and activated during exercise, its role in exercise-induced cardioprotection remains unknown. This study investigated whether modulation of eNOS activation during IR could participate in the exercise-induced cardioprotection against IR injury. Hearts isolated from sedentary or exercised rats (5 weeks training) were perfused with a Langendorff apparatus and IR performed in the presence or absence of NOS inhibitors [N-nitro-L-arginine methyl ester, L-NAME or N5-(1-iminoethyl)-L-ornithine, L-NIO] or tetrahydrobiopterin (BH?). Exercise training protected hearts against IR injury and this effect was abolished by L-NAME or by L-NIO treatment, indicating that exercise-induced cardioprotection is eNOS dependent. However, a strong reduction of eNOS phosphorylation at Ser1177 (eNOS-PSer1177) and of eNOS coupling during early reperfusion was observed in hearts from exercised rats (which showed higher eNOS-PSer1177 and eNOS dimerization at baseline) in comparison to sedentary rats. Despite eNOS uncoupling, exercised hearts had more S-nitrosylated proteins after early reperfusion and also less nitro-oxidative stress, indexed by lower malondialdehyde content and protein nitrotyrosination compared to sedentary hearts. Moreover, in exercised hearts, stabilization of eNOS dimers by BH4 treatment increased nitro-oxidative stress and then abolished the exercise-induced cardioprotection, indicating that eNOS uncoupling during IR is required for exercise-induced myocardial cardioprotection. Based on these results, we hypothesize that in the hearts of exercised animals, eNOS uncoupling associated with the improved myocardial antioxidant capacity prevents excessive NO synthesis and limits the reaction between NO and O?·- to form peroxynitrite (ONOO?), which is cytotoxic. PMID:24105420

Farah, C; Kleindienst, A; Bolea, G; Meyer, G; Gayrard, S; Geny, B; Obert, P; Cazorla, O; Tanguy, S; Reboul, Cyril

2013-10-09

274

Blue Native electrophoresis to study mitochondrial and other protein complexes  

Microsoft Academic Search

The biogenesis and maintenance of mitochondria relies on a sizable number of proteins. Many of these proteins are organized into complexes, which are located in the mitochondrial inner membrane. Blue Native polyacrylamide gel electrophoresis (BN-PAGE) is a method for the isolation of intact protein complexes. Although it was initially used to study mitochondrial respiratory chain enzymes, it can also be

Leo G. J Nijtmans; Nadine S Henderson; Ian J Holt

2002-01-01

275

The biogenesis of mitochondria 26  

Microsoft Academic Search

The vegetative segregation of parental and recombinant mitochondrial (cytoplasmic) genomes of Saccharomyces cerevisiae were compared by experiments involving the micromanipulation of early zygotic buds. Recombinant mitochondrial genomes are formed rapidly upon zygote formation and initial zygote buds are frequently composed of varying proportions of recombinant and parental type gnomes, which then all segregate in a similar fashion. Evidence suggesting that

H. B. Lukins; Jillian R. Tate; G. W. Saunders; Anthony W. Linnane

1973-01-01

276

Novel mitochondrial targets for neuroprotection  

PubMed Central

Mitochondrial dysfunction contributes to the pathophysiology of acute neurologic disorders and neurodegenerative diseases. Bioenergetic failure is the primary cause of acute neuronal necrosis, and involves excitotoxicity-associated mitochondrial Ca2+ overload, resulting in opening of the inner membrane permeability transition pore and inhibition of oxidative phosphorylation. Mitochondrial energy metabolism is also very sensitive to inhibition by reactive O2 and nitrogen species, which modify many mitochondrial proteins, lipids, and DNA/RNA, thus impairing energy transduction and exacerbating free radical production. Oxidative stress and Ca2+-activated calpain protease activities also promote apoptosis and other forms of programmed cell death, primarily through modification of proteins and lipids present at the outer membrane, causing release of proapoptotic mitochondrial proteins, which initiate caspase-dependent and caspase-independent forms of cell death. This review focuses on three classifications of mitochondrial targets for neuroprotection. The first is mitochondrial quality control, maintained by the dynamic processes of mitochondrial fission and fusion and autophagy of abnormal mitochondria. The second includes targets amenable to ischemic preconditioning, e.g., electron transport chain components, ion channels, uncoupling proteins, and mitochondrial biogenesis. The third includes mitochondrial proteins and other molecules that defend against oxidative stress. Each class of targets exhibits excellent potential for translation to clinical neuroprotection.

Perez-Pinzon, Miguel A; Stetler, R Anne; Fiskum, Gary

2012-01-01

277

Synergistic effect of cAMP and palmitate in promoting altered mitochondrial function and cell death in HepG2 cells  

PubMed Central

Saturated free fatty acids (FFAs), e.g. palmitate, have long been shown to induce toxicity and cell death in various types of cells. In this study, we demonstrate that cAMP synergistically amplifies the effect of palmitate on the induction of cell death in human hepatocellular carcinoma cell line, HepG2 cells. Elevation of cAMP level in palmitate treated cells led to enhanced mitochondrial fragmentation, mitochondrial reactive oxygen species (ROS) generation and mitochondrial biogenesis. Mitochondrial fragmentation precedes mitochondrial ROS generation and mitochondrial biogenesis, and may contribute to mitochondrial ROS overproduction and subsequent mitochondrial biogenesis. Fragmentation of mitochondria also facilitated the release of cytotoxic mitochondrial proteins, such as Smac, from the mitochondria and subsequent activation of caspases. However, cell death induced by palmitate and cAMP was caspase-independent and mainly necrotic.

Zhang, Linxia; Seitz, Linsey C.; Abramczyk, Amy M.; Chan, Christina

2009-01-01

278

Relationship between exercise induced dyspnea and functional capacity with doppler-derived diastolic function'  

PubMed

BACKGROUND: Dyspnea is the frequent cause of exercise intolerance and physical inactivity among patients referred for exercise tolerance test. Diastolic dysfunction has shown significant correlation with exercise capacity and exercise induced dyspnea. To find out the frequency of diastolic dysfunction (DD) and the relationships between impaired exercise capacity and exercise induced dyspnea with DD by Doppler-derived indices among patients referred for stress test in a tertiary care hospital of Karachi. METHODS: For this study 135 consecutive patients who were referred for stress test at our non-invasive lab were screened for eligibility. Patients with valvular pathology, atrial fibrillation (AF) and coronary artery disease (CAD) were excluded. Stress test was performed on treadmill using Bruce protocol. Assessment of diastolic function as determined by trans-mitral flow velocity pattern was carried at baseline and at peak exercise. We evaluated impaired exercise capacity and exercise induced dyspnea using validated Borg Scale among study subjects. RESULTS: Study subjects 88% were males, mean age was 46 ± 16 years, BMI 27 ± 5 kg/m2, prevalence of diabetes mellitus (DM) 15%, hypertension 28% and smoking 21%. Exercise induced DD occurred among 44.6%. Patients with exercise induced DD had lower exercise capacity (9.2 vs. 10.2 METS; p = 0.04) and higher Borg Scale (5.2 vs. 4.0; p < 0.001). DD at baseline was present in 25(26%) of patients so they were excluded from the study. Five patients develop ischemia during stress test so were also excluded. So final analysis was done on 105 patients. Among patients without DD at baseline, there was significant vicariate linear inverse correlation between post exercise E/A ratio and Borg scale (r = -0.23; p = 0.02) and exercise capacity was assessed by exercise duration and MET (r-0.825; p = 0.04). Multivariate regression analysis revealed post exercise E/A ratio as an independent determinant of severity of exercise induced dyspnea and impaired exercise tolerance. CONCLUSION: DD is significantly associated with impaired functional capacity and dyspnea among patients referred for exercise tolerance test. PMID:23587172

Nasim, Sumera; Nadeem, Najaf; Zahidie, Aysha; Sharif, Tabbasum

2013-04-15

279

Evaluation of exercise-induced acute renal failure in renal hypouricemia using Tc99m DTPA renography  

Microsoft Academic Search

We present a case of a thirty-eight-year-old man who had exercise-induced acute renal failure (exercise-induced ARF). He experienced\\u000a oliguria, general fatigue, and vague discomfort in the lower abdomen after he exercised. As he had suffered from hypouricemia\\u000a before, he was diagnosed as having exercise-induced ARF associated with hypouricemia. Enhanced computed tomography (CT) images\\u000a showed patchy wedge-shaped contrast enhancement on his

Hidemi Nishida; Hayato Kaida; Masatoshi Ishibashi; Kenkichi Baba; Keisuke Kouno; Seiya Okuda

2005-01-01

280

Mitochondrial complex III ROS regulate adipocyte differentiation  

PubMed Central

SUMMARY Adipocyte differentiation is characterized by an increase in mitochondrial metabolism. However it is not known whether the increase in mitochondrial metabolism is essential for differentiation or a byproduct of the differentiation process. Here, we report that primary human mesenchymal stem cells undergoing differentiation into adipocytes display an early increase in mitochondrial metabolism, biogenesis, and ROS generation. This early increase in mitochondrial metabolism and ROS generation was dependent on mTORC1 signaling. Mitochondrial targeted antioxidants inhibited adipocyte differentiation which was rescued by the addition of exogenous hydrogen peroxide. Genetic manipulation of mitochondrial complex III revealed ROS generated from this complex is required to initiate adipocyte differentiation. These results indicate that mitochondrial metabolism and ROS generation are not simply a consequence of differentiation, but are a causal factor in promoting adipocyte differentiation.

Tormos, Kathryn V.; Anso, Elena; Hamanaka, Robert B.; Eisenbart, James; Joseph, Joy; Kalyanaraman, Balaraman; Chandel, Navdeep S.

2011-01-01

281

Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage  

PubMed Central

Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely.

Hrelia, Silvana

2013-01-01

282

Exercise-induced central fatigue: a review of the literature with implications for dance science research.  

PubMed

The complex interplay between cortical and subcortical networks essential to motor performance is altered when muscles fatigue. The construct of exercise-induced human muscle fatigue has been attributed largely to the loss of a peripheral muscle's ability to produce force. Far less understood is "central fatigue," the result of alterations in central nervous system function. Central fatigue manifests as inadequate motor drive to the muscles and can occur even at sub-maximal levels of voluntary force. This study reviews the literature on exercise-induced central fatigue and its impact on motor performance. In reviewing conditions that may contributed to central fatigue, it addresses perceived exertion and repetitive strain and their relationship to central fatigue. Evidence supporting possible training protocols designed to offset central fatigue, while speculative, will be cited as potential areas of investigation for dance scientists. PMID:23759479

Batson, Glenna

2013-01-01

283

Progressive strenuous exercise induces the expression of HSP70 in rat skeletal muscles and myocardium  

Microsoft Academic Search

This study investigated the exercise-induced synthesis and accumulation of heat shock protein 70 (HSP70) after progressive strenuous exercise in rat soleus, plantaris, and myocardium. Sprague-Dawley rats were randomly assigned to one of six groups, one control group and five exercise groups, divided by intensity and duration of exercise. Skeletal muscles and heart were dissected immediately after last performance. The levels

Young-Oh Shin; Jae-Keun Oh; Jun-Sang Bae; Mi-Young Lee; Jeong-Beom Lee; Hun-Mo Yang; Young-Ki Min; Takaaki Matsumoto

2004-01-01

284

Mannitol as a Challenge Test to Identify Exercise-induced Bronchoconstriction in Elite Athletes  

Microsoft Academic Search

Bronchial provocation tests provide objective criteria for asthma of temperature and humidity (7). To overcome some of these and exercise-induced bronchoconstriction (EIB) and were recom- problems, the eucapnic voluntary hyperpnea (EVH) chal- mended to justify the use of inhaled 2-agonists by athletes at the lenge with dry air (8-10) has been used and recommended Winter Olympics 2002. Eucapnic voluntary hyperpnea

Karen Holzer; Sandra D. Anderson; Hak-Kim Chan; Jo Douglass

285

Diagnostic approach to chronic exercise-induced leg pain. A review.  

PubMed

The patient presenting with complaints of chronic exercise-induced lower leg pain can be a diagnostic challenge. Although myriad specialized diagnostic studies and modalities are at one's disposal, emphasis on a logical history and physical usually can identify the underlying cause without exposing the patient to any unnecessary testing. A well-directed history and physical, coupled with an understanding of the current state of knowledge regarding the pathophysiology and pathomechanics of shin splints, helps meet this challenge effectively. PMID:11417156

Hester, J T

2001-04-01

286

An update on exercise-induced bronchoconstriction with and without asthma  

Microsoft Academic Search

Exercise-induced bronchoconstriction (EIB) is defined as transient, reversible bronchoconstriction that develops after strenuous\\u000a exercise. It is a heterogeneous syndrome made up of a spectrum of phenotypes ranging from the asymptomatic military recruit\\u000a whose condition is detected by diagnostic exercise challenge to the athlete with known asthma to the elite athlete for whom\\u000a EIB represents an overuse or injury syndrome. If

Chris Randolph

2009-01-01

287

Study of the Cardiovascular Effects of Clenbuterol in Exercise-Induced Asthma  

Microsoft Academic Search

The protective effect of clenbuterol on exercise-induced asthma was studied in 14 patients with aspecific bronchial hyperreactivity. The selectivity of clenbuterol for ?2-receptors was also studied. Patients were selected according to spirometric criteria: reduced dynamic indexes of respiratory function after exercise and, particularly, forced expiratory volume at 1 s (FEV1) decreased by at least 20% compared with initial values. A

M. Di Gioacchino; A. Mezzetti; M. Mancini; M. D. Guglielmi; E. Lo Medico; G. Proietti Franceschilli; L. Marzio; F. Cuccurullo

1987-01-01

288

Exercise-induced silent myocardial ischemia and coronary morbidity and mortality in middle-aged men  

Microsoft Academic Search

OBJECTIVESWe investigated the prognostic significance of exercise-induced silent myocardial ischemia in both high and low risk men with no prior coronary heart disease (CHD).BACKGROUNDSilent ischemia predicts future coronary events in patients with CHD, but there is little evidence of its prognostic significance in subjects free of CHD.METHODSWe investigated the association of silent ischemia, as defined by ST depression during and

Jari A Laukkanen; Sudhir Kurl; Timo A Lakka; Tomi-Pekka Tuomainen; Rainer Rauramaa; Riitta Salonen; Jaakko Eränen; Jukka T Salonen

2001-01-01

289

Inspiratory Muscle Training in Exercise-Induced Paradoxical Vocal Fold Motion  

Microsoft Academic Search

Summary: The purpose of the study was to determine if inspiratory muscle training (IMT) would result in increased inspiratory muscle strength, reduced perception of exertional dyspnea, and improved measures of maximal exercise effort in an athlete with exercise-induced paradoxical vocal fold motion (PVFM). The participant, an 18-year-old woman, had a 2-year history of acute dyspnea with exertion during soccer games.

Barbara A. Mathers-Schmidt; L. R. Brilla

2005-01-01

290

Islet transplantation in diabetic rats normalizes basal and exercise-induced energy metabolism  

Microsoft Academic Search

Summary  Transplantation of islets of Langerhans in diabetic rats normalizes resting glucose and insulin levels, but it remains unclear whether islet transplantation restores resting and exercise-induced energy metabolism. Therefore, we compared energy metabolism in islet transplanted rats with energy metabolism in normal controls and in streptozotocin-induced diabetic rats. Indirect calorimetry was applied before, during, and after moderate swimming exercise. Blood was

H. Houwing; L. Benthem; P. T. R. Van Suylichem; J. Van der Leest; J. H. Strubbe; A. B. Steffens

1995-01-01

291

Exercise-induced increase in core temperature does not disrupt a behavioral measure of sleep  

Microsoft Academic Search

O’Connor, P. J., M. J. Breus, and S. D. Youngstedt. Exercise-induced Increase in Core Temperature Does Not Disrupt a Behavioral Measure of Sleep. PHYSIOL BEHAV 64(3) 213–217, 1998.—On separate nights 90 to 30 min before typical bedtime, eight physically active men completed three conditions: seated rest, low-intensity and moderate-intensity cycle exercise. Low-and moderate-intensity exercise had no significant effect on sleep

Patrick J O’Connor; Michael J Breus; Shawn D Youngstedt

1998-01-01

292

Exercise-induced hormone responses in girls at different stages of sexual maturation  

Microsoft Academic Search

The dependence of exercise-induced hormone responses on sexual maturation was tested in a 3-year longitudinal experiment\\u000a on 34 girls (aged 11–12 years at the beginning). Sexual maturation was evaluated by Tanners five-stage scale. Children cycled\\u000a for 20-min at 60% maximal oxygen uptake once a year. Cortisol, insulin, growth hormone, ?-oestradiol, progesterone and testosterone\\u000a concentrations in venous blood were determined by

Atko Viru; Livian Laaneots; Kalle Karelson; Tamara Smirnova; Mehis Viru

1998-01-01

293

Efficacy of omeprazole for the prevention of exercise-induced gastritis in racing Alaskan sled dogs.  

PubMed

Exercise-induced gastritis and gastric ulcers are common in humans and horses, and recently have been described in racing sled dogs. The cause of exercise-induced gastric disease is not completely understood in any species, but pharmacologic suppression of acid secretion is an effective treatment in humans and horses. Thus, we tested the hypothesis that omeprazole, a proton-pump inhibitor shown to reduce gastric acid secretion in dogs, would reduce the severity of exercise-induced gastric disease. Three teams of 16 dogs each competing in the 2002 Iditarod Sled Dog Race were recruited for participation. Within each team, dogs were randomly assigned to either treatment (20 mg omeprazole PO q24h) or placebo. Treatments were administered until either completion of the race or withdrawal of an individual dog from competition. Gastric endoscopy was performed in all dogs 24 hours after completion or withdrawal, and the gastric mucosa was scored by using a subjective severity score (0 = normal, 3 = numerous bleeding ulcers). Treatment with omeprazole significantly reduced mean gastricseverity score compared to placebo (omeprazole: 0.65 +/- 0.17, placebo: 1.09 +/- 0.18; P = .028), but also was associated with increased frequency of diarrhea during the race (omeprazole 54%, placebo 21%; P = .017). Examination of our data suggests that omeprazole may be an effective treatment for exercise-induced gastric disease in racing sled dogs. However, further investigation regarding the cause and clinical relevance of diarrhea associated with omeprazole treatment must be conducted before omeprazole can be recommended for routine prophylactic treatment in these athletes. PMID:12683615

Davis, M S; Willard, M D; Nelson, S L; McCullough, S M; Mandsager, R E; Roberts, J; Payton, M E

294

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina  

SciTech Connect

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

Kugiyama, K.; Yasue, H.; Okumura, K.; Goto, K.; Minoda, K.; Miyagi, H.; Matsuyama, K.; Kojima, A.; Koga, Y.; Takahashi, M.

1988-11-01

295

Eccentric exercise-induced muscle damage dissociates the lactate and gas exchange thresholds  

Microsoft Academic Search

We tested the hypothesis that exercise-induced muscle damage would increase the ventilatory ([Vdot]E) response to incremental\\/ramp cycle exercise (lower the gas exchange threshold) without altering the blood lactate profile, thereby dissociating the gas exchange and lactate thresholds. Ten physically active men completed maximal incremental cycle tests before (pre) and 48 h after (post) performing eccentric exercise comprising 100 squats. Pulmonary gas

Rosemary C. Davies; Ann V. Rowlands; David C. Poole; Andrew M. Jones; Roger G. Eston

2011-01-01

296

Incidence of exercise induced hypoxemia in elite endurance athletes at sea level  

Microsoft Academic Search

Summary  Recent evidence suggests that exercise-induced hypoxemia (EIH) may occur in healthy trained endurance athletes. However, at present, no data exist to describe the regularity of EIH in athletes or non-athletes. Therefore, the purpose of the present investigation was to determine the incidence of EIH during exercise in healthy subjects varying in physical fitness. Subjects (N=68) performed an incremental cycle ergometer

Scott K. Powers; Stephen Dodd; John Lawler; Greg Landry; Michael Kirtley; Tipton McKnight; Stephen Grinton

1988-01-01

297

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina  

Microsoft Academic Search

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol\\/kg body weight of magnesium sulfate and after placebo on different days. In all patients,

Kiyotaka Kugiyama; Hirofumi Yasue; Ken Okumura; Kazuo Goto; Kotako Minoda; Hiroo Miyagi; Koshi Matsuyama; Akihiro Kojima; Yukinori Koga; Mutsumasa Takahashi

1988-01-01

298

Exercise-induced inflammatory reaction affects electromyographic changes in skeletal muscle during dynamic contractions in humans  

Microsoft Academic Search

In order to assess the role of exercise-induced inflammatory reactions on electromyographic (EMG) changes in humans, we have recorded, during a 3-min dynamic handgrip exercise at a high strength (112 w), the surface EMG and the compound evoked muscle action potential (M-wave) in control conditions, and this after ingestion of a well known cyclooxygenase blocker i.e. acetylsalicylic acid (ASA), either

Marc Gainnier; Fabrice Michel; Pierre Fontanari; Stéphane Delpierre; Yves Jammes

2001-01-01

299

EFFECT OF FLEXIBILITY TRAINING ON SYMPTOMS OF EXERCISE-INDUCED MUSCLE DAMAGE: A PRELIMINARY STUDY  

Microsoft Academic Search

Exercise-induced muscle damage (EIMD) is characterized by loss of strength, increase in muscle stiffness, swelling, and soreness. The aim of this study was to assess the effects of flexibility training of the hamstring muscle group on symptoms of EIMD. Fourteen males (mean ± standard deviation: age = 20.6 ± 0.8 years; mass = 77.3 ± 10.4 kg; height = 1.77

Roger G. Eston; Ann V. Rowlands; David Coulton; James McKinney; Nigel P. Gleeson

2007-01-01

300

Initial metabolic state and exercise-induced endotoxaemia are unrelated to gastrointestinal symptoms during exercise  

Microsoft Academic Search

The aim of the study was to investigate the association between the initial metabolic state and exercise-induced endotoxaemia on the appearance of gastrointestinal symptoms (GIS) during exer- cise. Eleven males (36.6 ± 4.9 yrs, 1.7 ± 0.1 m, 74.5 ± 7.7 kg, DEXA body fat % 17.2 ± 6.6, VO2max 57.4 ± 7.4 ml·kg -1 ·min-1) underwent two isoenergetic diets

José Moncada-Jiménez; Eric Plaisance; Michael L. Mestek; Felipe Araya-Ramírez; Lance Ratcliff; James K. Taylor; Peter W. Grandjean; Luis F. AragónVargas

2009-01-01

301

Involvement of Endogenous Endothelin1 in Exercise-Induced Redistribution of Tissue Blood Flow  

Microsoft Academic Search

Background—Endothelin-1 (ET-1) is a potent endothelium-derived vasoconstrictor peptide. Exercise results in a significant redistribution of tissue blood flow, which greatly increases blood flow in active muscles but decreases it in the splanchnic circulation. We reported that exercise causes an increase of ET-1 production in the internal organ and then hypothesized that ET-1 participates in the exercise-induced redistribution of tissue blood

Seiji Maeda; Takashi Miyauchi; Motoyuki Iemitsu; Takumi Tanabe; Yoko Irukayama-Tomobe; Katsutoshi Goto; Iwao Yamaguchi; Mitsuo Matsuda

2010-01-01

302

Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia  

SciTech Connect

To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).

Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A. (Hamamatsu Univ. School of Medicine, Shizuoka (Japan))

1990-10-01

303

Exercise-induced stress enhances mammary tumor growth in rats: Beneficial effect of the hormone melatonin  

Microsoft Academic Search

We hypothesized that intense exercise training (forced swimming for 30 min, 5 days\\/week) may enhance the progression of mammary\\u000a carcinogenesis through the involvement of stress hormones, such as catecholamines and prolactin, which can promote breast\\u000a cancer. After the appearance of the DMBA-induced tumors in Sprague-Dawley rats, the effect was evaluated of exercise-induced\\u000a stress (with or without administration of the hormone

María del Carmen Sáez; Carmen Barriga; Ana Beatriz Rodríguez; Eduardo Ortega

2007-01-01

304

Exhaled nitric oxide level during and after heavy exercise in athletes with exercise-induced hypoxaemia  

Microsoft Academic Search

Endogenous nitric oxide (NO) is an important mediator of vasodilatation, bronchodilatation and lung inflammation. We hypothesised that the exhaled NO level may be modified in some endurance-trained athletes during and after intense exercise. Nine athletes with exercise-induced hypoxaemia (EIH), 12 athletes without EIH and 10 untrained subjects exercised for 15 min at 90% maximal oxygen consumption (&Vitdot;O2max). Exhaled NO was

Pascale Kippelen; Corinne Caillaud; Emmanuelle Robert; Kaouthar Masmoudi; Christian Préfaut

2002-01-01

305

Acid reflux into the oesophagus does not influence exercise-induced airway narrowing in bronchial asthma  

Microsoft Academic Search

Objectives:A few studies on small patient series have investigated the relationship between gastroesophageal reflux and bronchial responsiveness as expressed by exercise-induced bronchoconstriction (EIB), with non-conclusive results. The aim of this study was to evaluate whether the presence of acid in the oesophagus may influence EIB.Methods:45 patients with bronchial asthma underwent spirometry, exercise challenge on bicycle ergometer and 24 h oesophageal

M Ferrari; F Bonella; L Benini; P Ferrari; F De Iorio; R Testi; V Lo Cascio

2008-01-01

306

Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students  

Microsoft Academic Search

Background: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. Objective: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. Methods: A questionnaire asking about the occurrence of FEIAn in school students was sent to

Yukoh Aihara; Yuriko Takahashi; Takeshi Kotoyori; Toshihiro Mitsuda; Reiko Ito; Michiko Aihara; Zenro Ikezawa; Shumpei Yokota

2001-01-01

307

Lower limb compression garment improves recovery from exercise-induced muscle damage in young, active females  

Microsoft Academic Search

This study aimed to investigate the efficacy of lower limb compression as a recovery strategy following exercise-induced muscle\\u000a damage (EIMD). Seventeen female volunteers completed 10 × 10 plyometric drop jumps from a 0.6-m box to induce muscle damage.\\u000a Participants were randomly allocated to a passive recovery (n = 9) or a compression treatment (n = 8) group. Treatment group volunteers wore full leg compression stockings for

John R. Jakeman; Chris Byrne; Roger G. Eston

2010-01-01

308

Alpha 1 -adrenergic blockade reduces exercise-induced regional myocardial ischemia in dogs  

Microsoft Academic Search

The effect of selective a1-adrenoceptor blockade on regional myocardial blood flow and contractile function during exercise-induced myocardial ischemia was determined in nine dogs having chronic single vessel coronary stenosis (ameroid constrictor). Treadmill exercise performed after ß-adrenoceptor blockade (1.0 mg\\/kg i.v. propranolol), to block potential prejunctional effects recently recognized with a-blockade, elicited severe regional myocardial ischemia with a steady-state reduction of

B. D. Guth; T. Miura; E. Thaulow; G. Heusch; John Ross

1993-01-01

309

Detection of exercise-induced ischemia by changes in B-type natriuretic peptides  

Microsoft Academic Search

OBJECTIVES The purpose of this study was to examine the effect of exercise-induced ischemia on levels of B-type natriuretic peptide (BNP) and its inactive N-terminal fragment (NT-pro-BNP) and to determine whether measurement of these peptides can improve the diagnostic accuracy of exercise testing. BACKGROUND The ability of exercise testing to detect coronary artery disease (CAD) is limited by modest sensitivity

Robert S. Foote; Justin D. Pearlman; Alan H. Siegel; Kiang-Teck J. Yeo

2005-01-01

310

Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle  

Microsoft Academic Search

Peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1? and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found

Shin-ichi Ikeda; Takako Kizaki; Shukoh Haga; Hideki Ohno; Tohru Takemasa

2008-01-01

311

Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle  

SciTech Connect

Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1{alpha} and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1{alpha} protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1{alpha} expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1{alpha} and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions.

Ikeda, Shin-ichi [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 (Japan); Kizaki, Takako [Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan); Haga, Shukoh [Department of Exercise Physiology, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397 (Japan); Ohno, Hideki [Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan); Takemasa, Tohru [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 (Japan)], E-mail: takemasa@taiiku.tsukuba.ac.jp

2008-04-04

312

Exercise-induced asthma: critical analysis of the protective role of montelukast  

PubMed Central

Exercise-induced asthma/exercise-induced bronchospasm (EIA/EIB) is a prevalent and clinically important disease affecting young children through older adulthood. These terms are often used interchangeably and the differences are not clearly defined in the literature. The pathogenesis of EIA/EIB may be different in those with persistent asthma compared to those with exercise-induced symptoms only. The natural history of EIA is unclear and may be different for elite athletes. Leukotriene biology has helped the understanding of EIB. The type and intensity of exercise are important factors for EIB. Exercise participation is necessary for proper development and control of EIA is recommended. Symptoms of EIB should be confirmed by proper testing. Biologic markers may also be helpful in diagnosis. Not all exercise symptoms are from EIB. Many medication and nonpharmacologic treatments are available. Asthma education is an important component of managing EIA. Many medications have been tested and the comparisons are complicated. Montelukast is a US Food and Drug Administration-approved asthma and EIB controller and has a number of potential advantages to other asthma medications including short onset of action, ease of use, and lack of tolerance. Not all patients improve with montelukast and rescue medication should be available.

Carver, Terrence W

2009-01-01

313

The effect of sports specialization on musculus quadriceps function after exercise-induced muscle damage.  

PubMed

The primary aim of the present study was to examine the effect of eccentric exercise-induced (100 submaximal eccentric contractions at an angular velocity of 60° s?¹, with 20-s rest intervals) muscle damage on peripheral and central fatigue of quadriceps muscle in well-trained long-distance runners, sprint runners, volleyball players, and untrained subjects. We found that (i) indirect symptoms of exercise-induced muscle damage (prolonged decrease in maximal voluntary contraction, isokinetic concentric torque, and electrically induced (20 Hz) torque) were most evident in untrained subjects, while there were no significant differences in changes of muscle soreness and plasma creatine kinase 48 h after eccentric exercise between athletes and untrained subjects; (ii) low-frequency fatigue was greater in untrained subjects and volleyball players than in sprint runners and long-distance runners; (iii) in all subjects, electrically induced (100 Hz) torque decreased significantly by about 20%, while central activation ratio decreased significantly by about 8% in untrained subjects and sprint runners, and by about 3%-5% in long-distance runners and volleyball players. Thus, trained subjects showed greater resistance to exercise-induced muscle damage for most markers, and long-distance runners had no advantage over sprint runners or volleyball players. PMID:22050132

Skurvydas, Albertas; Brazaitis, Marius; Venck?nas, Tomas; Kamandulis, Sigitas; Stanislovaitis, Aleksas; Zuoza, Aurelijus

2011-11-03

314

The transcriptional coactivator PGC-1? mediates exercise-induced angiogenesis in skeletal muscle  

PubMed Central

Peripheral arterial disease (PAD) affects 5 million people in the US and is the primary cause of limb amputations. Exercise remains the single best intervention for PAD, in part thought to be mediated by increases in capillary density. How exercise triggers angiogenesis is not known. PPAR? coactivator (PGC)-1? is a potent transcriptional co-activator that regulates oxidative metabolism in a variety of tissues. We show here that PGC-1? mediates exercise-induced angiogenesis. Voluntary exercise induced robust angiogenesis in mouse skeletal muscle. Mice lacking PGC-1? in skeletal muscle failed to increase capillary density in response to exercise. Exercise strongly induced expression of PGC-1? from an alternate promoter. The induction of PGC-1? depended on ?-adrenergic signaling. ?-adrenergic stimulation also induced a broad program of angiogenic factors, including vascular endothelial growth factor (VEGF). This induction required PGC-1?. The orphan nuclear receptor ERR? mediated the induction of VEGF by PGC-1?, and mice lacking ERR? also failed to increase vascular density after exercise. These data demonstrate that ?-adrenergic stimulation of a PGC-1?/ERR?/VEGF axis mediates exercise-induced angiogenesis in skeletal muscle.

Chinsomboon, Jessica; Ruas, Jorge; Gupta, Rana K.; Thom, Robyn; Shoag, Jonathan; Rowe, Glenn C.; Sawada, Naoki; Raghuram, Srilatha; Arany, Zoltan

2009-01-01

315

Determinants of exercise-induced fat oxidation in obese women and men.  

PubMed

Endurance training at an intensity eliciting maximal fat oxidation may have a beneficial effect on body weight and glucose metabolism in obese patients. However, the exercise intensity at which maximal fat oxidation occurs and the factors limiting fat oxidation are not well studied in this population. Obese, otherwise healthy men (n=38) and women (n=91) performed an incremental exercise test up to exhaustion on a cycle ergometer. Substrate oxidation was estimated using indirect calorimetry. Magnetic resonance tomography and spectroscopy were conducted to assess body fat distribution and intramyocellular fat content. We determined the exercise intensity at which maximal body fat oxidation occurs and assessed whether body composition, body fat distribution, intramyocellular fat content, or oxidative capacity predict exercise-induced fat oxidation. Maximal exercise-induced fat oxidation was 0.30+/-0.02 g/min in men and 0.23+/-0.01 g/min in women (p<0.05). Exercise intensity at the maximum fat oxidation was 42+/-2.2% VO (2 max) in men and 43+/-1.7% VO (2 max) in women. With multivariate analysis, exercise-induced fat oxidation was related to fat-free mass, percent fat mass, and oxidative capacity, but not to absolute fat mass, visceral fat, or intramyocellular fat content. We conclude that in obese subjects the capacity to oxidize fat during exercise appears to be limited by skeletal muscle mass and oxidative capacity rather than the availability of visceral or intramyocellular fat. PMID:19937568

Haufe, S; Engeli, S; Budziarek, P; Utz, W; Schulz-Menger, J; Hermsdorf, M; Wiesner, S; Otto, C; Fuhrmann, J C; Luft, F C; Boschmann, M; Jordan, J

2009-11-23

316

Exercise-induced ST-segment depression in inferior leads during treadmill exercise testing and coronary artery disease  

Microsoft Academic Search

The exercise electrocardiogram is a commonly used non-invasive and inexpensive method for detection of electrocardiogram (ECG) changes secondary to myocardial ischemia. Reversible ST-segment depression is the characteristic finding associated with exercise-induced, demand-driven ischemia in patients with significant coronary obstruction but no flow limitation at rest. The exercise-induced ST-segment depression in inferior leads has been questioned and it has been reported

Salvatore Patanè; Filippo Marte; Giuseppe Dattilo; Rosario Grassi; Francesco Patanè

2010-01-01

317

No Influence of Noradrenaline Manipulation on Acute Exercise-Induced Increase of Brain-Derived Neurotrophic Factor  

Microsoft Academic Search

GOEKINT, M., E. HEYMAN, B. ROELANDS, R. NJEMINI, I. BAUTMANS, T. METS, and R. MEEUSEN. No Influence of Noradrenaline Manipulation on Acute Exercise-Induced Increase of Brain-Derived Neurotrophic Factor. Med. Sci. Sports Exerc., Vol. 40, No. 11, pp. 1990-1996, 2008. Purpose: To examine the influence of a selective noradrenaline reuptake inhibitor (SNRI) on the exercise-induced increase in circulating brain-derived neurotrophic factor

MAAIKE GOEKINT; ELSA HEYMAN; BART ROELANDS; ROSE NJEMINI; IVAN BAUTMANS; TONY METS; ROMAIN MEEUSEN

2008-01-01

318

Mitochondrial pathophysiology in Friedreich's ataxia.  

PubMed

Neurological examination indicates that Friedreich's ataxia corresponds to a mixed sensory and cerebellar ataxia, which affects the proprioceptive pathways. Neuropathology and pathophysiology of Friedreich's ataxia involves the peripheral sensory nerves, dorsal root ganglia, posterior columns, the spinocerebellar, and corticospinal tracts of the spinal cord, gracile and cuneate nuclei, dorsal nuclei of Clarke, and the dentate nucleus. Involvement of the myocardium and pancreatic islets of Langerhans indicates that it is also a systemic disease. The pathophysiology of the disease is the consequence of frataxin deficiency in the mitochondria and cells. Some of the biological consequences are currently recognized such as the effects on iron-sulfur cluster biogenesis or the oxidative status, but others deserve to be studied in depth. Among physiological aspects of mitochondria that have been associated with neurodegeneration and may be interesting to investigate in Friedreich's ataxia we can include mitochondrial dynamics and movement, communication with other organelles especially the endoplasmic reticulum, calcium homeostasis, apoptosis, and mitochondrial biogenesis and quality control. Changes in the mitochondrial physiology and transport in peripheral and central axons and mitochondrial metabolic functions such as bioenergetics and energy delivery in the synapses are also relevant functions to be considered. Thus, to understand the general pathophysiology of the disease and fundamental pathogenic mechanisms such as dying-back axonopathy, and determine molecular, cellular and tissue therapeutic targets, we need to discover the effect of frataxin depletion on mitochondrial properties and on specific cell susceptibility in the nervous system and other affected organs. PMID:23859341

González-Cabo, Pilar; Palau, Francesc

2013-08-01

319

Eukaryotic ribosome biogenesis at a glance.  

PubMed

Ribosomes play a pivotal role in the molecular life of every cell. Moreover, synthesis of ribosomes is one of the most energetically demanding of all cellular processes. In eukaryotic cells, ribosome biogenesis requires the coordinated activity of all three RNA polymerases and the orchestrated work of many (>200) transiently associated ribosome assembly factors. The biogenesis of ribosomes is a tightly regulated activity and it is inextricably linked to other fundamental cellular processes, including growth and cell division. Furthermore, recent studies have demonstrated that defects in ribosome biogenesis are associated with several hereditary diseases. In this Cell Science at a Glance article and the accompanying poster, we summarise the current knowledge on eukaryotic ribosome biogenesis, with an emphasis on the yeast model system. PMID:24172536

Thomson, Emma; Ferreira-Cerca, Sébastien; Hurt, Ed

2013-11-01

320

Short-term exercise training protects against doxorubicin-induced cardiac mitochondrial damage independent of HSP72.  

PubMed

Doxorubicin (Dox) is an antitumor agent used in cancer treatment, but its clinical use is limited due to cardiotoxicity. Although exercise training can defend against Dox-mediated cardiac damage, the means for this cardioprotection remain unknown. To investigate the mechanism(s) responsible for exercise training-induced cardioprotection against Dox-mediated cardiotoxicity, we tested a two-pronged hypothesis: 1) exercise training protects against Dox-induced cardiotoxicity by preventing Dox-mediated mitochondrial damage/dysfunction and increased oxidative stress and 2) exercise training-induced cardiac expression of the inducible isoform of the 70-kDa heat shock protein 72 (HSP72) is essential to achieve exercise training-induced cardioprotection against Dox toxicity. Animals were randomly assigned to sedentary or exercise groups and paired with either placebo or Dox treatment (i.e., 20 mg/kg body wt ip Dox hydrochloride 24 h before euthanasia). Dox administration resulted in cardiac mitochondrial dysfunction, activation of proteases, and apoptosis. Exercise training increased cardiac antioxidant enzymes and HSP72 protein abundance and protected cardiac myocytes against Dox-induced mitochondrial damage, protease activation, and apoptosis. To determine whether exercise-induced expression of HSP72 in the heart is required for this cardioprotection, we utilized an innovative experimental strategy that successfully prevented exercise-induced increases in myocardial HSP72 levels. However, prevention of exercise-induced increases in myocardial HSP72 did not eliminate the exercise-induced cardioprotective phenotype that is resistant to Dox-mediated injury. Our results indicate that exercise training protects against the detrimental side effects of Dox in cardiac myocytes, in part, by protecting mitochondria against Dox-mediated damage. However, this exercise-induced cardioprotection is independent of myocardial HSP72 levels. Finally, our data are consistent with the concept that increases in cardiac mitochondrial antioxidant enzymes may contribute to exercise-induced cardioprotection. PMID:20833957

Kavazis, Andreas N; Smuder, Ashley J; Min, Kisuk; Tümer, Nihal; Powers, Scott K

2010-09-10

321

Exercise-induced hemostatic alterations are detectable by rotation thrombelastography (ROTEM): A marathon study.  

PubMed

Rotation thrombelastography (ROTEM) provides a whole blood assay that allows the assessment of plasmic- and platelet-related hemostasis in a single-step procedure. In our current study, we focused on the capability of the method to detect hemostatic alterations induced by physical exercise, enrolling 33 healthy participants of the Dusseldorf Marathon 2006. Venous blood drawn immediately before and after finishing the marathon was analyzed by a rotational thrombelastograph (Pentapharm, Munich, Germany). On initiation of blood coagulation by recalcification, standard ROTEM parameters were determined. Comparison of the results obtained before and after the physical exercise was performed using the Student t test for paired samples. As a result, the mean clotting time (CT) determined from blood samples obtained immediately after the marathon was significantly shorter (662.9 + or - 67.8 seconds vs 505.6 + or - 97.3 seconds, P = .002) and the mean maximal clot firmness was significantly broader (48.4 +/- 6.6 mm vs 51.5 +/- 4.5 mm, P = .0004) when compared to results obtained before the physical exercise. Differences between mean clot formation times (CFTs; 280.6 + 96 seconds vs 270.4 + or - 73.8 seconds) and mean alpha angles (45.9 degrees + or - 8 degrees vs 47.8 degrees + or - 5.8 degrees ) before and after the marathon were not statistically significant. Remarkably, some participants showed opposed results, particularly prolongation of CT and narrowing of maximum clot firmness (MCF). Our study demonstrates that ROTEM is sensitive to exercise-induced hemostatic alterations. The method appears to be capable of detecting even distinct changes in hemostasis in a single-step procedure. Further analyses are needed to clarify which hemostasis parameters influence ROTEM results and which ROTEM results are independent predictors of exercise-induced alterations of plasmic and platelet function. This might help to explain interindividual differences in exercise-induced alterations of hemostasis. PMID:19696040

Sucker, Christoph; Zotz, Rainer B; Senft, Beate; Scharf, Rudiger E; Kröger, Knut; Erbel, Raimund; Möhlenkamp, Stefan

2009-08-19

322

Exercise-induced DNA damage: is there a relationship with inflammatory responses?  

PubMed

Both a systemic inflammatory response as well as DNA damage has been observed following exhaustive endurance exercise. Hypothetically, exercise-induced DNA damage might either be a consequence of inflammatory processes or causally involved in inflammation and immunological alterations after strenuous prolonged exercise (e.g. by inducing lymphocyte apoptosis and lymphocytopenia). Nevertheless, up to now only few studies have addressed this issue and there is hardly any evidence regarding a direct relationship between DNA or chromosomal damage and inflammatory responses in the context of exercise. The most conclusive picture that emerges from available data is that reactive oxygen and nitrogen species (RONS) appear to be the key effectors which link inflammation with DNA damage. Considering the time-courses of inflammatory and oxidative stress responses on the one hand and DNA effects on the other the lack of correlations between these responses might also be explained by too short observation periods. This review summarizes and discusses the recent findings on this topic. Furthermore, data from our own study are presented that aimed to verify potential associations between several endpoints of genome stability and inflammatory, immune-endocrine and muscle damage parameters in competitors of an Ironman triathlon until 19 days into recovery. The current results indicate that DNA effects in lymphocytes are not responsible for exercise-induced inflammatory responses. Furthermore, this investigation shows that inflammatory processes, vice versa, do not promote DNA damage, neither directly nor via an increased formation of RONS derived from inflammatory cells. Oxidative DNA damage might have been counteracted by training- and exercise-induced antioxidant responses. However, further studies are needed that combine advanced -omics based techniques (transcriptomics, proteomics) with state-of-the-art biochemical biomarkers to gain more insights into the underlying mechanisms. PMID:19203084

Neubauer, Oliver; Reichhold, Stefanie; Nersesyan, Armen; König, Daniel; Wagner, Karl-Heinz

2008-01-01

323

Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains  

PubMed Central

New neurons are continuously born in the hippocampus of several mammalian species throughout adulthood. Adult neurogenesis represents a natural model for understanding how to grow and incorporate new nerve cells into pre-existing circuits in the brain. Finding molecules or biological pathways that increase neurogenesis has broad potential for regenerative medicine. One strategy is to identify mouse strains that display large versus small increases in neurogenesis in response to wheel running so the strains can be contrasted to find common genes or biological pathways associated with enhanced neuron formation. Therefore, mice from 12 different isogenic strains were housed with or without running wheels for 43 days to measure the genetic regulation of exercise-induced neurogenesis. The first 10 days mice received daily injections of BrdU to label dividing cells. Neurogenesis was measured as the total number of BrdU cells co-expressing NeuN mature neuronal marker in the hippocampal granule cell layer by immunohistochemistry. Exercise increased neurogenesis in all strains, but the magnitude significantly depended on genotype. Strain means for distance run on wheels, but not distance traveled in cages without wheels, were significantly correlated with strain mean level of neurogenesis. Further, certain strains displayed greater neurogenesis than others for a fixed level of running. Strain means for neurogenesis under sedentary conditions were not correlated with neurogenesis under runner conditions suggesting that different genes influence baseline versus exercise-induced neurogenesis. Genetic contributions to exercise-induced hippocampal neurogenesis suggest that it may be possible to identify genes and pathways associated with enhanced neuroplastic responses to exercise.

Clark, Peter J.; Kohman, Rachel A.; Miller, Daniel S.; Bhattacharya, Tushar K.; Brzezinska, Weronika J.; Rhodes, Justin S.

2011-01-01

324

Mitochondrial gene expression is regulated at multiple levels and differentially in the heart and liver by thyroid hormones  

Microsoft Academic Search

Biogenesis of the oxidative phosphorylation system (OXPHOS) requires the coordinated expression of the nuclear and the mitochondrial\\u000a genomes. Thyroid hormones play an important role in cell growth and differentiation and are one of the main effectors in mitochondrial\\u000a biogenesis. To determine how mtDNA expression is regulated, we have investigated the response of two different tissues, the\\u000a heart and liver, to

Erika Fernández-Vizarra; José A. Enriquez; Acisclo Pérez-Martos; Julio Montoya; Patricio Fernández-Silva

2008-01-01

325

Where to from here for exercise-induced bronchoconstriction: the unanswered questions.  

PubMed

The role of epithelial injury is an unanswered question in those with established asthma and in elite athletes who develop features of asthma and exercise-induced bronchorestriction (EIB) after years of training. The movement of water in response to changes in osmolarity is likely to be an important signal to the epithelium that may be central to the onset of EIB. It is generally accepted that the mast cell and its mediators play a major role in EIB and the presence of eosinophils is likely to enhance EIB severity. PMID:23830134

Hallstrand, Teal S; Kippelen, Pascale; Larsson, Johan; Bougault, Valérie; van Leeuwen, Janneke C; Driessen, Jean M M; Brannan, John D

2013-03-29

326

Exercise-induced muscle damage and the repeated bout effect: evidence for cross transfer  

Microsoft Academic Search

We examined whether a prior bout of eccentric exercise in the elbow flexors provided protection against exercise-induced muscle\\u000a damage in the contralateral arm. Fifteen males (age 22.7 ± 2.1 years; height 178.6 ± 6.8 cm, mass 75.8 ± 9.3 kg) were randomly\\u000a assigned to two groups who performed two bouts of 60 eccentric contractions (30°\\/s) separated by 2 weeks: ipsilateral (n = 7, both bouts performed in the same arm), contralateral (n = 8,

Chelsea Starbuck; Roger G. Eston

327

Exercise-induced hypoglycaemia in IDDM patients treated with a short-acting insulin analogue  

Microsoft Academic Search

Summary  In order to examine the effect of shortacting insulin analogue on the exercise-induced hypoglycaemia in insulin-dependent\\u000a diabetes mellitus (IDDM) patients we compared the glycaemic response of 40 min cycle ergometer exercise performed either shortly\\u000a (40 min) or later (180 min) after a breakfast meal and subcutaneous injection of either short-acting insulin analogue [Lys(B28)\\u000a Pro(B29)] or soluble human insulin (Humulin Regular)

J. A. Tuominen; S.-L. Karonen; L. Melamies; G. Bolli; V. A. Koivisto

1995-01-01

328

Exercise-induced plasma volume expansion and post-exercise parasympathetic reactivation  

Microsoft Academic Search

The purpose of this study was to investigate the effect of exercise-induced plasma volume expansion on post-exercise parasympathetic\\u000a reactivation. Before (D0) and 2 days after (D+2) a supramaximal exercise session, 11 men (21.4 ± 2.6 years and BMI = 23.0 ± 1.4) performed 6-min of submaximal running where\\u000a heart rate (HR) recovery (HRR) and HR variability (HRV) indices were calculated during the first 10 min of recovery. Relative

M. Buchheit; P. B. Laursen; H. Al Haddad; S. Ahmaidi

2009-01-01

329

Protective effects of repeated short sprints in exercise-induced asthma.  

PubMed Central

Many asthmatic patients demonstrate bronchial lability with a six-minute period of exercise, which is characterised by an initial bronchodilatation followed by bronchoconstriction. This early bronchodilatation response has been further analysed by investigation of the effects of repeated 30-second sprints before and after a six-minute run. It was found that these repeated short sprints did not induce bronchoconstriction, resulted in less bronchoconstriction after a subsequent six-minute run, and caused bronchodilatation if exercise-induced bronchoconstriction was present. It is postulated that this effect may be related to an increase in circulating catecholamines or altered vagal-sympathetic balance.

Schnall, R P; Landau, L I

1980-01-01

330

Haemodynamic implications of exercise-induced myocardial ischaemia in patients with recent inferior myocardial infarction.  

PubMed

Two hundred and forty patients with recent inferior myocardial infarction were studied by a symptom-limited ergometric test with haemodynamic monitoring (triple lumen tip-thermistor Swan-Ganz catheter) in order to investigate and quantify the haemodynamic effects of exercise-induced myocardial ischaemia in post-infarct patients and to assess whether the ST-segment changes give any indication of the degree of ventricular impairment. One hundred and thirteen patients showed no ST-segment changes during excercise; ST-segment elevation in leads with abnormal Q wave occurred in 14 patients, ST-segment depression was recorded in 88 subjects, and both ST-segment elevation and depression were found in 27 patients. In subjects with no ST-segment shift, as well as in those with exercise-induced ST-segment elevation, the resting and exertional haemodynamic patterns were normal or nearly normal. In subjects showing ST-segment depression or both ST-segment elevation and depression during exercise the mean pulmonary wedge pressure was abnormally elevated (at peak exercise 25 +/- 8 and 24 +/- 7 mm Hg, respectively). However, 31% of these showed a normal haemodynamic pattern either at rest or during exercise. The number of leads with ST-segment depression and the sum of ST-segment depressions in standard ECG does not reliably indicate the degree of ischaemia-dependent left ventricular impairment. In contrast, in patients grouped on the basis of time of ST depression appearance, the lower the ischaemic threshold the more severe was the left ventricular impairment. Finally, to assess the relative role of both scar and ischaemia in producing left ventricular dysfunction, the haemodynamic patterns of patients with and without exercise-induced ST-segment depression were compared in subsets with similar echocardiographic wall asynergy extent (inferior, infero-apical, infero-septo-apical). Among patients with small or medium-sized scar, the exertional left ventricular filling pressure was normal in patients with no ST-segment depression and abnormally elevated in those with ST-segment depression. In patients with large infarct, the exercise pulmonary wedge pressure was similarly elevated in both the ischaemic and non-ischaemic group, but in the latter cardiac output increase during exercise was limited. In conclusion: in patients with recent inferior myocardial infarction exercise-induced ST-segment depression is a marker of left ventricular impairment when the ischaemic threshold is low. The impairment consists of an abnormal elevation of left ventricular filling pressure in all subjects, associated with a reduced increase in cardiac output in patients with large infarct. PMID:3391183

De Vito, F; Giordano, A; Giannuzzi, P; Tavazzi, L

1988-04-01

331

Mitochondrial Myopathies  

MedlinePLUS

NINDS Mitochondrial Myopathies Information Page Table of Contents (click to jump to sections) What is Mitochondrial Myopathies? Is there ... is being done? Clinical Trials Organizations What is Mitochondrial Myopathies? Mitochondrial myopathies are a group of neuromuscular ...

332

The arithmetic of centrosome biogenesis.  

PubMed

How do cells regulate centrosome number? A canonical duplication cycle generates two centrosomes from one in most proliferating cells. Centrioles are key to this process, and molecules such as centrins, SAS-4 and ZYG-1 govern daughter centriole formation. Cdk2 activity probably couples centrosome duplication with the S phase, and a licensing mechanism appears to limit centrosome duplication to once per cell cycle. However, such mechanisms must be altered in some cells--for example, spermatocytes--in which centrosome duplication and DNA replication are uncoupled. There are also alternative pathways of centrosome biogenesis. For example, one centrosome is reconstituted from two gametes at fertilization; in this case, the most common strategy involves differential contributions of centrioles and pericentriolar material (PCM) from each gamete. Furthermore, centrioles can sometimes form de novo from no apparent template. This occurs, for instance, in the early mouse embryo and in parthenogenetic species and might rely on a pre-existing seed that resides within PCM but is not visible by ultrastructural analysis. PMID:15075224

Delattre, Marie; Gönczy, Pierre

2004-04-01

333

Disruption of microRNA biogenesis confers resistance to ER stress-induced cell death upstream of the mitochondrion.  

PubMed

Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis promotes tumor development is not clearly understood. Here we show that loss of miRNA biogenesis increased resistance to endoplasmic reticulum (ER) stress-induced cell death. We observed that HCT116 cells with a DICER hypomorphic mutation (Exn5/Exn5) or where DICER or DROSHA were knocked down were resistant to ER stress-induced cell death. Extensive analysis revealed little difference in the unfolded protein response (UPR) of WT compared to Exn5/Exn5 HCT116 cells upon ER stress treatment. However, analysis of the intrinsic apoptotic pathway showed that resistance occurred upstream of the mitochondria. In particular, BAX activation and dissipation of mitochondrial membrane potential was attenuated, and there was altered expression of BCL-2 family proteins. These observations demonstrate a key role for miRNAs as critical modulators of the ER stress response. In our model, downregulation of miRNA biogenesis delays ER stress-induced apoptosis. This suggests that disrupted miRNA biogenesis may contribute to cancer progression by inhibiting ER stress-induced cell death. PMID:23977393

Cawley, Karen; Logue, Susan E; Gorman, Adrienne M; Zeng, Qingping; Patterson, John; Gupta, Sanjeev; Samali, Afshin

2013-08-19

334

Neither gender nor menstrual cycle phase influences exercise-induced lymphocyte apoptosis in untrained subjects.  

PubMed

Lymphocyte apoptosis increases following maximal exercise. Estrogen hormones (E2) have been shown to protect lymphocytes from apoptosis in vitro, but it is unknown whether they can attenuate the apoptotic response to maximal exercise. The purpose of this study was to examine the effect of menstrual cycle variation on exercise-induced lymphocyte apoptosis in humans following exercise. Untrained healthy young men and regularly menstruating women not using hormonal contraceptives volunteered for the study. Women performed a maximal effort treadmill test for VO2 max once in the follicular phase (FOL) and once in the mid-luteal phase (ML) of their cycles. Men completed two VO2 max tests with periods of time between tests matched to those of the female subjects. Blood was collected before (PRE) and immediately after exercise (POST), and analyzed for apoptotic lymphocytes and estradiol. E2 concentrations in women were significantly greater during ML versus during FOL, both PRE and POST (p<0.0001). The percent of exercise-induced lymphocyte apoptosis was similar between women (23.2%+/-1.0%) and men (21.5%+/-0.4%). In women, the apoptotic response to maximal exercise was similar regardless of menstrual cycle phase (FOL=23.7%+/-0.9%, ML=22.7%+/-1.1%). Although elevated female sex hormones in vitro may exert anti-apoptotic effects, these data suggest that in vivo concentrations confer no protection to lymphocytes during exhaustive exercise. PMID:17510683

Navalta, James W; Sedlock, Darlene A; Park, Kyung-Shin; McFarlin, Brian K

2007-06-01

335

Skin testing with food, codeine, and histamine in exercise-induced anaphylaxis.  

PubMed

A 33-year-old Chinese woman with exercise-induced anaphylaxis after ingesting Chinese seafood noodle soup, was studied for skin test reactivity to food, histamine, and codeine. Prick skin tests were negative for shrimp, wheat, and chicken soup base, but were positive at 5 to 6 mm (wheal diameter) to the whole broth after it had been combined with the other ingredients. No significant (> 3 mm) wheals were observed in eight controls who were simultaneously tested with the broth. To assess the role of exercise, three series of skin tests were performed with histamine, codeine, and whole broth before and after aerobic exercise on two occasions. Codeine elicited consistent increases in wheal size after exercise compared with pre-exercise skin tests. Histamine and whole broth wheal sizes did not increase significantly. Three control subjects also had codeine and histamine skin tests before and after exercise, No exercise-associated increases were noted for codeine. Potential insights into mast cell abnormalities in exercise-induced anaphylaxis may be gained by skin testing patterns with codeine and other mast cell degranulating agents. PMID:8507042

Lin, R Y; Barnard, M

1993-06-01

336

Colostrum supplementation protects against exercise - induced oxidative stress in skeletal muscle in mice  

PubMed Central

Background This study examined the effects of bovine colostrum on exerciseinduced modulation of antioxidant parameters in skeletal muscle in mice. Adult male BALB/c mice were randomly divided into four groups (control, colostrum alone, exercise and exercise with colostrum) and each group had three subgroups (day 0, 21 and 42). Colostrum groups of mice were given a daily oral supplement of 50 mg/kg body weight of bovine colostrum and the exercise group of mice were made to exercise on the treadmill for 30 minutes per day. Total antioxidants, lipid hydroperoxides, xanthine oxidase and super oxide dismutase level was assayed from the homogenate of hind limb skeletal muscle. Results Exercise—induced a significant oxidative stress in skeletal muscles as evidenced by the elevated lipid hydroperoxides and xanthine oxidase levels. There was a significant decrease in skeletal muscle total antioxidants and superoxide dismutase levels. Daily colostrum supplement significantly reduced the lipid hydroperoxides and xanthine oxidase enzyme level and increased the total antioxidant levels in the leg muscle. Conclusion Thus, the findings of this study showed that daily bovine colostrum supplementation was beneficial to skeletal muscle to reduce the oxidant-induced damage during muscular exercise.

2012-01-01

337

Possible in vivo tolerance of human polymorphonuclear neutrophil to low-grade exercise-induced endotoxaemia.  

PubMed Central

To address the question of whether translocation of bacterial lipopolysaccharide (LPS) into the blood could be involved in the process of exercise-induced polymorphonuclear neutrophil (PMN) activation, 12 healthy male subjects who took part in a sprint triathlon (1.5 km river swim, 40 km bicycle race, 10 km road race) were studied. While there was no detectable amount of endotoxin in the blood samples drawn at rest, exercise was followed by the appearance of circulating endotoxin molecules at the end of competition in four subjects, and after one and 24 h recovery in three and seven athletes, respectively. The concentrations of plasma granulocyte myeloperoxidase ([MPO]), were significantly higher immediately after exercise and one hour later-than baseline values (P<0.001). This variable returned to pre-race levels the day after exercise, despite the presence of detectable amounts of LPS, at that time, in seven athletes. The absence of significant correlation (r=0.26; P=0.383) and temporal association between [MPO] and plasma endotoxin levels led us to conclude that endotoxaemia was not involved in the process of exercise-induced PMN degranulation observed in our subjects.

Camus, G; Nys, M; Poortmans, J R; Venneman, I; Monfils, T; Deby-Dupont, G; Juchmes-Ferir, A; Deby, C; Lamy, M; Duchateau, J

1998-01-01

338

Familial paroxysmal exercise-induced dystonia: atypical presentation of autosomal dominant GTP-cyclohydrolase 1 deficiency.  

PubMed

Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced after many minutes of exercise, and was never present at rest, or on initiation of movements. In addition, family members suffered restless legs syndrome (RLS), depression, and adult-onset Parkinsonism. The index case had low cerebrospinal fluid neurotransmitters and pterins. The PED and RLS stopped on initiation of L-Dopa therapy. Both live family members were found to have a nonsense mutation (p.E84X) in exon 1 of the GTP-cyclohydrolase 1 (GCH-1) gene. We propose that GCH-1 mutations should be considered a genetic cause of familial PED, especially if additional clinical features of monoaminergic deficiency are present in affected individuals. PMID:20187889

Dale, Russell C; Melchers, Anna; Fung, Victor S C; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

2010-02-19

339

Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography  

SciTech Connect

Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent.

Kurata, C.; Sakata, K.; Taguchi, T.; Kobayashi, A.; Yamazaki, N. (Hamamatsu Univ. School of Medicine (Japan))

1990-03-01

340

Ginsenoside-Rg1 Protects the Liver against Exhaustive Exercise-Induced Oxidative Stress in Rats  

PubMed Central

Despite regular exercise benefits, acute exhaustive exercise elicits oxidative damage in liver. The present study determined the hepatoprotective properties of ginsenoside-Rg1 against exhaustive exercise-induced oxidative stress in rats. Forty rats were assigned into vehicle and ginsenoside-Rg1 groups (0.1?mg/kg bodyweight). After 10-week treatment, ten rats from each group performed exhaustive swimming. Estimated oxidative damage markers, including thiobarbituric acid reactive substance (TBARS) (67%) and protein carbonyls (56%), were significantly (P < 0.01) elevated after exhaustive exercise but alleviated in ginsenoside-Rg1 pretreated rats. Furthermore, exhaustive exercise drastically decreased glutathione (GSH) content (?79%) with concurrent decreased superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) activities. However, these changes were attenuated in Rg1 group. Additionally, increased xanthine oxidase (XO) activity and nitric oxide (NO) levels after exercise were also inhibited by Rg1 pretreatment. For the first time, our findings provide strong evidence that ginsenoside-Rg1 can protect the liver against exhaustive exercise-induced oxidative damage.

Korivi, Mallikarjuna; Hou, Chien-Wen; Huang, Chih-Yang; Lee, Shin-Da; Hsu, Ming-Fen; Yu, Szu-Hsien; Chen, Chung-Yu; Liu, Yung-Yang; Kuo, Chia-Hua

2012-01-01

341

An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus  

PubMed Central

With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging.

Pereira, Ana C.; Huddleston, Dan E.; Brickman, Adam M.; Sosunov, Alexander A.; Hen, Rene; McKhann, Guy M.; Sloan, Richard; Gage, Fred H.; Brown, Truman R.; Small, Scott A.

2007-01-01

342

Versatility of MicroRNA Biogenesis  

PubMed Central

MicroRNAs (miRNAs) are short single-stranded RNA molecules that regulate gene expression. MiRNAs originate from large primary (pri) and precursor (pre) transcripts that undergo various processing steps along their biogenesis pathway till they reach their mature and functional form. It is not clear, however, whether all miRNAs are processed similarly. Here we show that the ratio between pre-miRNA and mature miRNA forms varies between different miRNAs. Moreover, over-expression of several factors involved in miRNA biogenesis, including Exportin-5, Drosha, NF90a, NF45 and KSRP, displayed bidirectional effects on pre/mature miRNA ratios, suggesting their intricate biogenesis sensitivity. In an attempt to identify additional factors that might explain the versatility in miRNA biogenesis we have analyzed the contribution of two hnRNP family members, hnRNPH1 and hnRNPR. Knock-down or over-expression of these genes suggested that hnRNPR inhibits, whereas hnRNPH1 facilitates, miRNA processing. Overall, our results emphasize that miRNA biogenesis is versatile.

Volk, Naama; Shomron, Noam

2011-01-01

343

Versatility of MicroRNA biogenesis.  

PubMed

MicroRNAs (miRNAs) are short single-stranded RNA molecules that regulate gene expression. MiRNAs originate from large primary (pri) and precursor (pre) transcripts that undergo various processing steps along their biogenesis pathway till they reach their mature and functional form. It is not clear, however, whether all miRNAs are processed similarly. Here we show that the ratio between pre-miRNA and mature miRNA forms varies between different miRNAs. Moreover, over-expression of several factors involved in miRNA biogenesis, including Exportin-5, Drosha, NF90a, NF45 and KSRP, displayed bidirectional effects on pre/mature miRNA ratios, suggesting their intricate biogenesis sensitivity. In an attempt to identify additional factors that might explain the versatility in miRNA biogenesis we have analyzed the contribution of two hnRNP family members, hnRNPH1 and hnRNPR. Knock-down or over-expression of these genes suggested that hnRNPR inhibits, whereas hnRNPH1 facilitates, miRNA processing. Overall, our results emphasize that miRNA biogenesis is versatile. PMID:21572999

Volk, Naama; Shomron, Noam

2011-05-10

344

Therapeutic prospects for mitochondrial disease  

PubMed Central

Until even only a few years ago, the idea that effective therapies for human mitochondrial disorders resulting from dysfunction of the respiratory chain/oxidative phosphorylation system (OxPhos) could be developed was unimaginable. The obstacles to treating diseases caused by mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA), and which had the potential to affect nearly every organ system, seemed overwhelming. However, while clinically applicable therapies still remain largely in the future, the landscape has changed dramatically; we can now envision the possibility of treating some of these disorders. Among these are techniques to upregulate mitochondrial biogenesis, to enhance organellar fusion and fission, to “shift heteroplasmy,” and to eliminate the burden of mutant mtDNAs via cytoplasmic transfer.

Schon, Eric A.; DiMauro, Salvatore; Hirano, Michio; Gilkerson, Robert W.

2010-01-01

345

Biochemical and molecular characterization of photosystem I deficiency in the NCS6 mitochondrial mutant of maize  

Microsoft Academic Search

Interorganellar signaling interactions are poorly understood. The maize non-chromosomal stripe (NCS) mutants provide models to study the requirement of mitochondrial function for chloroplast biogenesis and photosynthesis. Previous work suggested that the NCS6 mitochondrial mutation, a cytochrome oxidase subunit 2 (cox2) deletion, is associated with a malfunction of Photosystem I (PSI) in defective chloroplasts of mutant leaf sectors (Gu et al.,

Shunxing Jiao; Jeffry M. Thornsberry; Thomas E. Elthon; Kathleen J. Newton

2005-01-01

346

A high copy number of yeast ?-glutamylcysteine synthetase suppresses a nuclear mutation affecting mitochondrial translation  

Microsoft Academic Search

A new temperature-sensitive nuclear mutant affecting the biogenesis of functional mitochondria has been identified. This pet mutant was formerly characterized by a complete block of mitochondrial translation at the restrictive temperature. The analysis of mitochondrial transcripts demonstrates the accumulation of precursors for the small ribosomal RNA. Transformation of the mutant with plasmids from gene banks identified a chromosomal DNA fragment

Thomas Lisowsky

1993-01-01

347

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases  

Microsoft Academic Search

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial\\u000a biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological\\u000a abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial\\u000a occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic

Tomohiro Nakamura; Stuart A. Lipton

2010-01-01

348

Detection of high-burden coronary artery disease by exercise-induced changes of the E/E' ratio.  

PubMed

To investigate whether exercise-induced changes of the E/E' average ratio can detect high-burden coronary artery disease (CAD) in patients with chest pain and normal left ventricular (LV) systolic function. The study population consisted of 359 patients admitted for chest pain (59.8 ± 9.8 years, 75% male). Patients underwent exercise echocardiography, scintigraphy and coronary angiography. The average of the lateral and septal ratios of early diastolic transmitral velocity to early diastolic tissue velocity (E/E') at baseline and immediately after exercise was calculated. Exercise induced wall motion abnormalities were also calculated. Coronary angiography showed flow limiting CAD in 238 patients (66%). The exercise-induced changes of E/E' average ratio had a sensitivity of 87.3% and a specificity of 75.2% for detection of flow limiting CAD, whereas myocardial scintigraphy showed 79.2% sensitivity and 80.1% specificity and exercise induced wall motion abnormalities had a sensitivity of 74.3% and a specificity of 66.9%. Likelihood ratio chi square showed an incremental value of the exercise-induced changes of E/E' average ratio over regional perfusion technique (from 121.37 to 194.15, P < 0.001) and over wall motion abnormalities (from 57.03 to 146.50, P < 0.001). The exercise-induced change of the E/E' average ratio detects flow limiting CAD in patients with chest pain and normal LV systolic function showing an incremental value over regional perfusion technique and wall motion abnormalities. PMID:21394613

Tsougos, Elias; Paraskevaidis, Ioannis; Dagres, Nikolaos; Varounis, Christos; Panou, Fotios; Karatzas, Dimitrios; Trapali, Xenia; Iliodromitis, Efstathios; Kremastinos, Dimitrios T

2011-03-11

349

Temperature- and exercise-induced gene expression and metabolic enzyme changes in skeletal muscle of adult zebrafish (Danio rerio)  

PubMed Central

Both exercise training and cold acclimatization induce muscle remodelling in vertebrates, producing a more aerobic phenotype. In ectothermic species exercise training and cold-acclimatization represent distinct stimuli. It is currently unclear if these stimuli act through a common mechanism or if different mechanisms lead to a common phenotype. The goal of this study was to survey responses that represent potential mechanisms responsible for contraction- and temperature-induced muscle remodelling, using an ectothermic vertebrate. Separate groups of adult zebrafish (Danio rerio) were either swim trained or cold acclimatized for 4 weeks. We found that the mitochondrial marker enzyme citrate synthase (CS) was increased by 1.5× in cold and by 1.3× with exercise (P < 0.05). Cytochrome c oxidase (COx) was increased by 1.2× following exercise training (P < 0.05) and 1.2× (P = 0.07) with cold acclimatization. However, only cold acclimatization increased ?-hydroxyacyl-CoA dehydrogenase (HOAD) compared to exercise-trained (by 1.3×) and pyruvate kinase (PK) relative to control zebrafish. We assessed the whole-animal performance outcomes of these treatments. Maximum absolute sustained swimming speed (Ucrit) was increased in the exercise trained group but not in the cold acclimatized group. Real-time PCR analysis indicated that increases in CS are primarily transcriptionally regulated with exercise but not with cold treatments. Both treatments showed increases in nuclear respiratory factor (NRF)-1 mRNA which was increased by 2.3× in cold-acclimatized and 4× in exercise-trained zebrafish above controls. In contrast, peroxisome proliferator-activated receptor (PPAR)-? mRNA levels were decreased in both experimental groups while PPAR-?1 declined in exercise training only. Moreover, PPAR-? coactivator (PGC)-1? mRNA was not changed by either treatment. In zebrafish, both temperature and exercise produce a more aerobic phenotype, but there are stimulus-dependent responses (i.e. HOAD and PK activities). While similar changes in NRF-1 mRNA suggest that common responses might underlie aerobic muscle remodelling there are distinct changes (i.e. CS and PPAR-?1 mRNA) that contribute to specific temperature- and exercise-induced phenotypes.

McClelland, Grant B; Craig, Paul M; Dhekney, Kalindi; Dipardo, Shawn

2006-01-01

350

Isoprenaline- and exercise-induced tachycardia in the assessment of ?-adrenoceptor blocking drugs; a comparison between tolamolol, practolol and propranolol  

PubMed Central

The effects of tolamolol, propranolol and practolol on both isoprenaline- and exercise-induced tachycardia have been studied in conscious dogs. Tolamolol was approximately equipotent to propranolol and 50 times more potent than practolol in antagonizing exercise-induced tachycardias, but was approximately 12 times less potent than propranolol and 8 times more potent than practolol in blocking isoprenaline-induced tachycardia. It is suggested that antagonism of the tachycardia induced by exercise affords a more meaningful assessment of the possible therapeutic potential of ?-adrenoceptor blocking drugs than does that induced by isoprenaline.

Adam, K. R.; Pullman, L. G.; Scholfield, P. C.

1973-01-01

351

The “SUN” Family: UTH1, an Ageing Gene, Is Also Involved in the Regulation of Mitochondria Biogenesis in Saccharomyces cerevisiae  

Microsoft Academic Search

Since it was shown in previous work that NCA3 (one of the four genes of the SUN family) is involved in mitochondrial protein synthesis regulation, the effect of the other members of this gene family was tested. UTH1 (but not SUN4 or SIM1) was also shown to interfere with mitochondria biogenesis. In ?uth1 cells, cytochromes aa3, c, and b were

N. M. Camougrand; M. Mouassite; G. M. Velours; M. G. Guérin

2000-01-01

352

Initial metabolic state and exercise-induced endotoxaemia are unrelated to gastrointestinal symptoms during exercise.  

PubMed

The aim of the study was to investigate the association between the initial metabolic state and exercise-induced endotoxaemia on the appearance of gastrointestinal symptoms (GIS) during exercise. Eleven males (36.6 ± 4.9 yrs, 1.7 ± 0.1 m, 74.5 ± 7.7 kg, DEXA body fat % 17.2 ± 6.6, VO2max 57.4 ± 7.4 ml·kg(-1)·min(-1)) underwent two isoenergetic diets designed to change their initial metabolic status by either depleting or maintaining their hepatic and muscular glycogen content. These diets and accompanying exercise sessions were performed by each participant in the days before completing a laboratory-based duathlon (5-km run, 30-km cycling, 10-km run). Blood samples were obtained before, immediately and 1- and 2-h following the duathlon for determination of insulin (IN), glucagon (GL), endotoxin, aspartic aminotransferase (AST), and alanine aminotransferase (ALT) markers. GIS were assessed by survey before and after exercise. Diet content produced a different energy status as determined by macronutrient content and the IN/GL ratio (p < 0.05), and mild exercise-induced endotoxaemia was observed in both experimental duathlons. Regardless of the diet, the AST/ALT ratio following exercise and in the recovery phase indicated hepatocyte and liver parenchyma structural damage. In spite of GIS, no significant correlations between endotoxin levels and GIS were found. In conclusion, increased markers of endotoxaemia observed with the high-intensity exercise were unrelated to hepatic function and/or GIS before and after exercise. Key pointsGastrointestinal symptoms before, during, and after a competition are reported by approximately 20%-50% of the athletes participating in endurance events such as marathon, cycling and triathlon.Energy status, exercise-induced endotoxaemia and liver structural damage might be related to gastrointestinal symptoms.In this study, gastrointestinal symptoms observed before and after endurance exercise were unrelated to endotoxin levels or hepatic structural damage. PMID:24149534

Moncada-Jimènez, José; Plaisance, Eric P; Mestek, Michael L; Araya-Ramirez, Felipe; Ratcliff, Lance; Taylor, James K; Grandjean, Peter W; Aragonvargas, Luis F

2009-06-01

353

Exercise-Induced Cognitive Plasticity, Implications for Mild Cognitive Impairment and Alzheimer's Disease  

PubMed Central

Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer’s disease (AD) and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe) functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ?4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak and Braak (1991) and Braak et al. (1993) we propose that the effects of exercise occur in two temporo-spatial continua of events. The “inward” continuum from isocortex (neocortex) to entorhinal cortex/hippocampus for amyloidosis and a reciprocal “outward” continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF) has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1) may mediate the exercise-induced response to exercise on BDNF, neurogenesis, and cognitive performance. It is also postulated to regulate brain amyloid ? (A?) levels by increased clearance via the choroid plexus. Growth factors, specifically fibroblast growth factor and IGF-1 receptors and/or their downstream signaling pathways may interact with the Klotho gene which functions as an aging suppressor gene. Neurons may not be the only cells affected by exercise. Glia (astrocytes and microglia), neurovascular units and the Fourth Element may also be affected in a differential fashion by the AD process. Analyses of these factors, as suggested by the multi-dimensional matrix approach, are needed to improve our understanding of this complex multi-factorial process, which is increasingly relevant to conquering the escalating and intersecting world-wide epidemics of dementia, diabetes, and sarcopenia that threaten the global healthcare system. Physical activity and interventions aimed at enhancing and/or mimicking the effects of exercise are likely to play a significant role in mitigating these epidemics, together with the embryonic efforts to develop cognitive rehabilitation for neurodegenerative disorders.

Foster, Philip P.; Rosenblatt, Kevin P.; Kuljis, Rodrigo O.

2011-01-01

354

Effects of nicardipine on cardiac volume at rest and during exercise-induced angina.  

PubMed

The action of nicardipine on cardiac volume, both at rest and during exercise-induced angina, was evaluated in 12 patients with angiographically-proven coronary artery disease. Nicardipine given to patients at rest reduced systemic vascular resistance and mean arterial pressure and increased heart rate and cardiac index. The left ventricular filling pressure, ejection fraction (EF), end-diastolic and end-systolic volumes were unchanged. During supine bicycle exercise, the reduction in systemic arterial blood pressure following nicardipine increased cardiac and stroke index and attenuated the rise in left ventricular filling pressure observed in the control exercise. The effects of nicardipine on EF, end-diastolic and end-systolic cardiac volumes were dependent on the baseline cardiac reserve. In patients with EF less than 50%, nicardipine improved EF and left ventricular exercise volumes. PMID:2862901

Silke, B; Verma, S P; Frais, M A; Hafizullah, M; Taylor, S H

1985-01-01

355

Exercise-induced left bundle branch block: an infrequent phenomenon: Report of two cases.  

PubMed

Exercise-induced left bundle branch block (EI-LBBB) is infrequent phenomenon. We present two patients with angina pectoris who developed EI-LBBB during exercise tolerance test. The first patient with typical angina pectoris had significant obstructive coronary artery disease (CAD) requiring percutaneous coronary intervention of multiple lesions including placement of drug eluting stents. The second patient had atypical chest pain without signs of CAD at all. EI-LBBB occurred at a heart rate of 80 bpm and 141 bpm in the first and second patient, respectively. EI-LBBB remained visible through the test till the recovery period in the first patient at a heart rate of 83 bpm and disappeared at 96 bpm in the second patient. Both patients with this infrequent phenomenon are discussed and the literature is reviewed. PMID:24109500

Said, Salah Am; Bultje-Peters, Marisa; Nijhuis, Rogier Lg

2013-09-26

356

Exercise-induced left bundle branch block: an infrequent phenomenon: Report of two cases  

PubMed Central

Exercise-induced left bundle branch block (EI-LBBB) is infrequent phenomenon. We present two patients with angina pectoris who developed EI-LBBB during exercise tolerance test. The first patient with typical angina pectoris had significant obstructive coronary artery disease (CAD) requiring percutaneous coronary intervention of multiple lesions including placement of drug eluting stents. The second patient had atypical chest pain without signs of CAD at all. EI-LBBB occurred at a heart rate of 80 bpm and 141 bpm in the first and second patient, respectively. EI-LBBB remained visible through the test till the recovery period in the first patient at a heart rate of 83 bpm and disappeared at 96 bpm in the second patient. Both patients with this infrequent phenomenon are discussed and the literature is reviewed.

Said, Salah AM; Bultje-Peters, Marisa; Nijhuis, Rogier LG

2013-01-01

357

Exercise-induced cognitive plasticity, implications for mild cognitive impairment and Alzheimer's disease.  

PubMed

Lifestyle factors such as intellectual stimulation, cognitive and social engagement, nutrition, and various types of exercise appear to reduce the risk for common age-associated disorders such as Alzheimer's disease (AD) and vascular dementia. In fact, many studies have suggested that promoting physical activity can have a protective effect against cognitive deterioration later in life. Slowing or a deterioration of walking speed is associated with a poor performance in tests assessing psychomotor speed and verbal fluency in elderly individuals. Fitness training influences a wide range of cognitive processes, and the largest positive impact observed is for executive (a.k.a. frontal lobe) functions. Studies show that exercise improves additional cognitive functions such as tasks mediated by the hippocampus, and result in major changes in plasticity in the hippocampus. Interestingly, this exercise-induced plasticity is also pronounced in APOE ?4 carriers who express a risk factor for late-onset AD that may modulate the effect of treatments. Based on AD staging by Braak and Braak (1991) and Braak et al. (1993) we propose that the effects of exercise occur in two temporo-spatial continua of events. The "inward" continuum from isocortex (neocortex) to entorhinal cortex/hippocampus for amyloidosis and a reciprocal "outward" continuum for neurofibrillary alterations. The exercise-induced hypertrophy of the hippocampus at the core of these continua is evaluated in terms of potential for prevention to stave off neuronal degeneration. Exercise-induced production of growth factors such as the brain-derived neurotrophic factor (BDNF) has been shown to enhance neurogenesis and to play a key role in positive cognitive effects. Insulin-like growth factor (IGF-1) may mediate the exercise-induced response to exercise on BDNF, neurogenesis, and cognitive performance. It is also postulated to regulate brain amyloid ? (A?) levels by increased clearance via the choroid plexus. Growth factors, specifically fibroblast growth factor and IGF-1 receptors and/or their downstream signaling pathways may interact with the Klotho gene which functions as an aging suppressor gene. Neurons may not be the only cells affected by exercise. Glia (astrocytes and microglia), neurovascular units and the Fourth Element may also be affected in a differential fashion by the AD process. Analyses of these factors, as suggested by the multi-dimensional matrix approach, are needed to improve our understanding of this complex multi-factorial process, which is increasingly relevant to conquering the escalating and intersecting world-wide epidemics of dementia, diabetes, and sarcopenia that threaten the global healthcare system. Physical activity and interventions aimed at enhancing and/or mimicking the effects of exercise are likely to play a significant role in mitigating these epidemics, together with the embryonic efforts to develop cognitive rehabilitation for neurodegenerative disorders. PMID:21602910

Foster, Philip P; Rosenblatt, Kevin P; Kuljiš, Rodrigo O

2011-05-06

358

Effects of virtual reality-enhanced exercise equipment on adherence and exercise-induced feeling states.  

PubMed

A field study was conducted to test the effectiveness of virtual reality-enhanced cardiovascular exercise equipment for increasing adherence and attendance in a mixed-sex adult sample. Attendance was significantly higher in the virtual reality-enhanced condition than in the conditions without virtual reality over the 14-wk. period. Adherence was also highest (83.33%) in the virtual-reality bicycle group. Postexercise feelings of positive engagement, revitalization, tranquility, and physical exhaustion, as measured by the Exercise-induced Feeling Inventory, did not differ among groups. Contrary to previous findings, Self-motivation Inventory scores were not associated with either attendance or adherence. While findings suggest that virtual-reality features may promote exercise adherence or attendance, it is not yet known what psychological variables they affect. Implications were drawn regarding the practical possibilities for exercise promotion. PMID:9399288

Annesi, J J; Mazas, J

1997-12-01

359

Physical exercise induces activation of NF-kappaB in human peripheral blood lymphocytes.  

PubMed

Current understanding of nuclear factor-kappaB (NF-kappaB) activation is derived mostly from in vitro studies, and in vivo human data are limited. This study provides first evidence showing that physical exercise (80% maximal O2 consumption, 1 h) may trigger NF-kappaB activation, as determined by electrophoretic mobility shift assay, in peripheral blood lymphocytes of physically fit young men. Supershift assay showed that the NF-kappaB protein complex contained the transcriptionally active p65 protein. Plasma levels of NF-kappaB-directed gene products such as tumor necrosis factor-alpha and interleukin-2 receptor confirmed that physical exercise caused NF-kappaB transactivation. Exercise-induced NF-kappaB activation in lymphocytes was associated with elevated levels of lipid peroxidation by-products in the plasma. PMID:11813986

Vider, J; Laaksonen, D E; Kilk, A; Atalay, M; Lehtmaa, J; Zilmer, M; Sen, C K

2001-12-01

360

Exercise-induced up-regulation of MMP-1 and IL-8 genes in endurance horses  

PubMed Central

Background The stress response is a critical factor in the training of equine athletes; it is important for performance and for protection of the animal against physio-pathological disorders. In this study, the molecular mechanisms involved in the response to acute and strenuous exercise were investigated using peripheral blood mononuclear cells (PBMCs). Results Quantitative real-time PCR (qRT-PCR) was used to detect modifications in transcription levels of the genes for matrix metalloproteinase-1 (MMP-1) and interleukin 8 (IL-8), which were derived from previous genome-wide expression analysis. Significant up-regulation of these two genes was found in 10 horses that had completed a race of 90–120 km in a time-course experimental design. Conclusion These results suggest that MMP-1 and IL-8 are both involved in the exercise-induced stress response, and this represents a starting point from which to understand the adaptive responses to this phenomenon.

Cappelli, Katia; Felicetti, Michela; Capomaccio, Stefano; Pieramati, Camillo; Silvestrelli, Maurizio; Verini-Supplizi, Andrea

2009-01-01

361

Exercise-related respiratory symptoms and exercise-induced bronchoconstriction in industrial bakers.  

PubMed

In order to assess prevalence and characteristics of exercise-related respiratory symptoms (ERRS) and exercise-induced bronchoconstriction (EIB) in industrial bakery, the authors performed a cross-sectional study including 57 bakers and an equal number of office workers studied as a control. Evaluation of examined subjects included completion of a questionnaire, skin prick tests to common inhalant and occupational allergens, spirometry, and exercise and histamine challenge. The authors found a similar prevalence of ERRS and EIB in both bakers and controls. EIB was significantly associated with atopy, asthma, family history of asthma, and positive histamine challenge in either group, whereas in bakers it was closely related to sensitization to occupational allergens (p = .032). Bronchial reaction to exercise was significantly higher in bakers with EIB (25.7% vs 19.2%; p = .021). These findings suggest that occupational exposure in industrial bakery may accentuate bronchoconstrictive response to exercise. PMID:23697696

Minov, Jordan B; Karadzinska-Bislimovska, Jovanka D; Vasilevska, Kristin V; Stoleski, Saso B; Mijakoski, Dragan G

2013-01-01

362

Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium  

PubMed Central

Objective To determine whether the Bezold?Jarisch reflex or enhancement of vagal nerves, which are preferentially distributed in the inferoposterior myocardium, results from exercise induced ischaemia in this region. Methods On the basis of exercise myocardial scintigraphy and coronary angiography, 145 patients were classified as follows: group I, 34 patients with inferoposterior ischaemia; group A, 32 with anterior ischaemia; and control, 79 without ischaemia. The relation between ischaemic areas and ECG leads with ST segment changes and vagal modulation assessed by heart rate variability (HRV) (high frequency (HF) component (0.15–0.40?Hz) and coefficient of HF component variance (CCVHF), which is the square root of HF divided by mean RR interval) were assessed. Results The rate of ST segment depression in any lead did not differ between group I and group A. HF and CCVHF were similar before exercise but higher in group I than in group A and the control group after exercise (mean (SEM) HF: 94 (17)?ms2, 41 (7)?ms2, and 45 (6)?ms2, respectively, p??=??0.021; CCVHF: 1.18 (0.09)%, 0.81 (0.07)%, and 0.89 (0.05)%, p??=?0.0053). Furthermore, the percentage change in CCVHF before and after exercise was higher in group I than in group A or controls (mean (SEM) 22 (10)%, ?24 (4)%, and ?21 (3)%, p?exercise induced inferoposterior ischaemia. Exercise ECG testing combined with HRV analysis would increase accuracy in the diagnosis of ischaemic areas in selected patients with angina pectoris.

Kawasaki, T; Azuma, A; Kuribayashi, T; Taniguchi, T; Asada, S; Kamitani, T; Kawasaki, S; Matsubara, H; Sugihara, H

2006-01-01

363

Rehydration with sodium-enriched coconut water after exercise-induced dehydration.  

PubMed

This crossover study assessed the effectiveness of plain water (PW), sports drink (SD), fresh young coconut water (CW) and sodium-enriched fresh young coconut water (SCW) on whole body rehydration (R) and plasma volume (PV) restoration after exercise-induced dehydration. Ten healthy male subjects ran at 65% of VO2max in an environmental temperature of 32.06 +/- 0.02 degree C with a relative humidity (rh) of 53.32 +/- 0.17% for 90 minutes to lose 3% body weight (BW). During the 2-hour rehydration period, subjects drank, in randomized order, PW, SD, CW or SCW equivalent to 120% of BW lost in three boluses representing 50, 40 and 30% of the fluid lost at 0, 30, and 60 minutes, respectively. In all trials subjects were still somewhat dehydrated even after the 2-hour rehydration period. Indexes of percent rehydration with PW, SD, CW and SCW were 58 +/- 2, 68 +/- 2, 65+/- 2 and 69 +/- 1%, respectively, with significantly better rehydration with SD and SCW. The rehydration indexes for SD and SCW were significantly lower than PW (p < 0.01). PV was restored to euhydration levels after 2 hours of rehydration with SD, CW and SCW but not with PW. The plasma glucose concentration were significantly higher when SD, CW and SCW were ingested. SCW was similar in sweetness to CW and SD but caused less nausea and stomach upset compared to SD and PW. In conclusion, ingesting SCW was as good as ingesting a commercial sports drink for whole body rehydration after exercise-induced dehydration but with better fluid tolerance. PMID:17883020

Ismail, I; Singh, R; Sirisinghe, R G

2007-07-01

364

Cognitive awareness of carbohydrate intake does not alter exercise-induced lymphocyte apoptosis  

PubMed Central

OBJECTIVE: The purpose of this investigation was to determine whether cognitive awareness of carbohydrate beverage consumption affects exercise?induced lymphocyte apoptosis, independent of actual carbohydrate intake. INTRODUCTION: Carbohydrate supplementation during aerobic exercise generally protects against the immunosuppressive effects of exercise. It is not currently known whether carbohydrate consumption or simply the knowledge of carbohydrate consumption also has that effect. METHODS: Endurance trained male and female (N ?=? 10) athletes were randomly assigned to one of two groups based on either a correct or incorrect cognitive awareness of carbohydrate intake. In the incorrect group, the subjects were informed that they were receiving the carbohydrate beverage but actually received the placebo beverage. Participants completed a 60?min ride on a cycle ergometer at 80% VO2peak under carbohydrate and placebo supplemented conditions. Venous blood samples were collected at rest and immediately after exercise and were used to determine the plasma glucose concentration, lymphocyte count, and extent of lymphocyte apoptosis. Cognitive awareness, either correct or incorrect, did not have an effect on any of the measured variables. RESULTS: Carbohydrate supplementation during exercise did not have an effect on lymphocyte count or apoptotic index. Independent of drink type, exercise resulted in significant lymphocytosis and lymphocyte apoptosis (apoptotic index at rest ?=? 6.3±3% and apoptotic index following exercise ?=? 11.6±3%, P<0.01). CONCLUSION: Neither carbohydrate nor placebo supplementation altered the typical lymphocyte apoptotic response following exercise. While carbohydrate supplementation generally has an immune?boosting effect during exercise, it appears that this influence does not extend to the mechanisms that govern exercise?induced lymphocyte cell death.

Navalta, James Wilfred; McFarlin, Brian Keith; Lyons, Scott; Arnett, Scott Wesley; Schafer, Mark Anthony

2011-01-01

365

Glycopyrrolate abolishes the exercise-induced increase in cerebral perfusion in humans.  

PubMed

Brain blood vessels contain muscarinic receptors that are important for cerebral blood flow (CBF) regulation, but whether a cholinergic receptor mechanism is involved in the exercise-induced increase in cerebral perfusion or affects cerebral metabolism remains unknown. We evaluated CBF and cerebral metabolism (from arterial and internal jugular venous O(2), glucose and lactate differences), as well as the middle cerebral artery mean blood velocity (MCA V(mean); transcranial Doppler ultrasound) during a sustained static handgrip contraction at 40% of maximal voluntary contraction (n = 9) and the MCA V(mean) during ergometer cycling (n = 8). Separate, randomized and counterbalanced trials were performed in control (no drug) conditions and following muscarinic cholinergic receptor blockade by glycopyrrolate. Glycopyrrolate increased resting heart rate from approximately 60 to approximately 110 beats min(-1) (P < 0.01) and cardiac output by approximately 40% (P < 0.05), but did not affect mean arterial pressure. The central cardiovascular responses to exercise with glycopyrrolate were similar to the control responses, except that cardiac output did not increase during static handgrip with glycopyrrolate. Glycopyrrolate did not significantly affect cerebral metabolism during static handgrip, but a parallel increase in MCA V(mean) (approximately 16%; P < 0.01) and CBF (approximately 12%; P < 0.01) during static handgrip, as well as the increase in MCA V(mean) during cycling (approximately 15%; P < 0.01), were abolished by glycopyrrolate (P < 0.05). Thus, during both cycling and static handgrip, a cholinergic receptor mechanism is important for the exercise-induced increase in cerebral perfusion without affecting the cerebral metabolic rate for oxygen. PMID:20660020

Seifert, Thomas; Fisher, James P; Young, Colin N; Hartwich, Doreen; Ogoh, Shigehiko; Raven, Peter B; Fadel, Paul J; Secher, Niels H

2010-07-21

366

Magnitude of Exercise-Induced ?-Endorphin Response Is Associated with Subsequent Development of Altered Hypoglycemia Counterregulation  

PubMed Central

Context: ?-Endorphin release in response to recurrent hypoglycemia is implicated in the pathogenesis of hypoglycemia-associated autonomic failure. Objective: We hypothesized that exercise-induced ?-endorphin release will also result in the deterioration of subsequent hypoglycemia counterregulation and that the counterregulatory response will negatively correlate with the degree of antecedent ?-endorphin elevation. Design, Setting, Participants, and Interventions: Sixteen healthy subjects (six females, aged 26 ± 4.3 yr, body mass index 26.1 ± 5.6 kg/m2) were studied with three experimental paradigms on 2 consecutive days. Day 1 consisted of one of the following: 1) two 90-min hyperinsulinemic hypoglycemic clamps (3.3 mmol/liter); 2) two 90-min hyperinsulinemic euglycemic clamps while subjects exercised at 60% maximal oxygen uptake; or 3) two 90-min hyperinsulinemic euglycemic clamps (control). Day 2 followed with hyperinsulinemic (396 ± 7 pmol/liter) stepped hypoglycemic clamps (5.0, 4.4, 3.9, and 3.3 mmol/liter plasma glucose steps). Main Outcome Measures: Day 2 hypoglycemia counterregulatory hormonal response and glucose turnover ([3-3H]-glucose) as indicators of recovery from hypoglycemia. Results: There was a significant inverse correlation between plasma ?-endorphin levels during exercise and catecholamine release during subsequent hypoglycemia. Subjects with an exercise-induced rise in ?-endorphin levels to above 25 pg/ml (n = 7) exhibited markedly reduced levels of plasma epinephrine and norepinephrine compared with control (2495 ± 306 vs. 4810 ± 617 pmol/liter and 1.9 ± 0.3 vs. 2.9 ± 0.4 nmol/liter, respectively, P < 0.01 for both). The rate of endogenous glucose production recovery in this group was also much lower than in controls (42 vs. 89%, P < 0.01). Conclusions: The physiological increase in ?-endorphin levels during exercise is associated with the attenuation of counterregulation during subsequent hypoglycemia.

Milman, Sofiya; Leu, James; Shamoon, Harry; Vele, Septimiu

2012-01-01

367

Exercise-Induced Blood Lactate Increase Does Not Change Red Blood Cell Deformability in Cyclists  

PubMed Central

Background The effect of exercise-induced lactate production on red blood cell deformability and other blood rheological changes is controversial, given heavy-exercise induces biochemical processes (e.g., oxidative stress) known to perturb haemorheology. The aim of the present study was to examine the haemorheological response to a short-duration cycling protocol designed to increase blood lactate concentration, but of duration insufficient to induce significant oxidative stress. Methods Male cyclists and triathletes (n?=?6; 27±7 yr; body mass index: 23.7±3.0 kg/m2; peak oxygen uptake 4.02±0.51 L/min) performed unloaded (0 W), moderate-intensity, and heavy-intensity cycling. Blood was sampled at rest and during the final minute of each cycling bout. Blood chemistry, blood viscosity, red blood cell aggregation and red blood cell deformability were measured. Results Blood lactate concentration increased significantly during heavy-intensity cycling, when compared with all other conditions. Methaemoglobin fraction did not change during any exercise bout when compared with rest. Blood viscosity at native haematocrit increased during heavy-intensity cycling at higher-shear rates when compared with rest, unloaded and moderate-intensity cycling. Heavy-intensity exercise increased the amplitude of red blood cell aggregation in native haematocrit samples when compared with all other conditions. Red blood cell deformability was not changed by exercise. Conclusion Acute exercise perturbs haemorheology in an intensity dose-response fashion; however, many of the haemorheological effects appear to be secondary to haemoconcentration, rather than increased lactate concentration.

Simmonds, Michael J.; Connes, Philippe; Sabapathy, Surendran

2013-01-01

368

The Free-Running Asthma Screening Test: An Approach to Screening for Exercise-Induced Asthma in Rural Alabama.  

ERIC Educational Resources Information Center

|This study documented the prevalence of exercise-induced asthma (EIA) in rural elementary schools, examining the use of a free-running asthma screening test and peak expiratory flow-rate measurement for school screening. Results indicated that 5.7% of the students had EIA. Absenteeism and poverty were related to EIA. (SM)|

Heaman, Doris J.; Estes, Jenny

1997-01-01

369

Effects of Postexercise Supplementation of Chicken Essence on the Elimination of Exercise-Induced Plasma Lactate and Ammonia  

Microsoft Academic Search

We investigated the effects of chicken essence (CE) supplementation on exercise-induced changes of lactate and ammonia during recovery. In this randomized, double blind, crossover study, twelve healthy subjects performed a single bout of exercise to exhaustion, and then consumed either a placebo or CE within 5-min of the exercise cessation. Blood samples were collected before exercise, at exhaustion (0 minute),

Hsin-I Lo; Daniel Tsi; Amabel CL Tan; Shyi-Wu Wang; Mei-Chich Hsu

370

Increased dietary protein attenuates C-reactive protein and creatine kinase responses to exercise-induced energy deficit  

Technology Transfer Automated Retrieval System (TEKTRAN)

We determined if dietary protein (P) modulates responses of C-reactive protein (CRP) and creatine kinase (CK), biomarkers of inflammation and muscle damage, during exercise-induced energy deficit (DEF). Thirteen healthy men (22 +/- 1 y, VO2peak 60 +/- 2 ml.kg-1.min-1) balanced energy expenditure (EE...

371

Dense-Core Secretory Granule Biogenesis  

NSDL National Science Digital Library

The dense-core secretory granule is a key organelle for secretion of hormones and neuropeptides in endocrine cells and neurons, in response to stimulation. Cholesterol and granins are critical for the assembly of these organelles at the trans-Golgi network, and their biogenesis is regulated quantitatively by posttranscriptional and posttranslational mechanisms.

Taeyoon Kim (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Marjorie C. Gondré-Lewis (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Irina Arnaoutova (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development); Y. Peng Loh (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development)

2006-04-01

372

[Molecular mechanisms of peroxisome biogenesis in yeasts].  

PubMed

Peroxisomes contain oxidases generating hydrogen peroxide, and catalase degrading this toxic compound. Another characteristic function of each eukaryotic peroxisome, from yeast to man, is fatty acid beta-oxidation. However, in peroxisomes a variety of other metabolic pathways are located. In fungi, peroxisomes contain enzymes involved in catabolism of unusual carbon and nitrogen sources (methanol, purines, D-amino acids, pipecolynic acid, sarcosine, glycolate, spermidine etc) as well as biosynthesis of lysine in yeasts and penicillin in mycelial fungi. Impairment of peroxisomal structure and functions causes many human disorders. The similar defects have been identified in yeast mutants defective in peroxisomal biogenesis. Peroxisomal biogenesis is actively studied during last two decades using uni- and multicellular model systems. It was observed that many aspects of peroxisomal biogenesis and proteins involved in this process display striking similarity between all eukaryotes, from yeasts to humans. Yeast is a convenient model system for this kind of research. Current review summarizes data on molecular events of peroxisomal biogenesis, functions of peroxine proteins, import of peroxisomal matrix and membrane proteins and on mechanisms of peroxisomedivision and inheritance. PMID:22642098

Sibirny?, A A

373

Biogenesis of small RNAs in animals  

Microsoft Academic Search

Small RNAs of 20–30 nucleotides can target both chromatin and transcripts, and thereby keep both the genome and the transcriptome under extensive surveillance. Recent progress in high-throughput sequencing has uncovered an astounding landscape of small RNAs in eukaryotic cells. Various small RNAs of distinctive characteristics have been found and can be classified into three classes based on their biogenesis mechanism

Jinju Han; V. Narry Kim; Mikiko C. Siomi

2009-01-01

374

The biogenesis and regulation of telomerase holoenzymes  

PubMed Central

Chromosome stability requires a dynamic balance of DNA loss and gain in each terminal tract of telomeric repeats. Repeat addition by a specialized reverse transcriptase, telomerase, has an important role in maintaining this equilibrium. Insights that have been gained into the cellular pathways for biogenesis and regulation of telomerase ribonucleoproteins raise new questions, particularly concerning the dynamic nature of this unique polymerase.

Collins, Kathleen

2010-01-01

375

Adrenaline but not noradrenaline is a determinant of exercise-induced lipid mobilization in human subcutaneous adipose tissue.  

PubMed

The relative contribution of noradrenaline (norepinephrine) and adrenaline (epinephrine) in the control of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise was evaluated in men treated with a somatostatin analogue, octreotide. Eight lean and eight obese young men matched for age and physical fitness performed 60 min exercise bouts at 50% of their maximal oxygen consumption on two occasions: (1) during i.v. infusion of octreotide, and (2) during placebo infusion. Lipolysis and local blood flow changes in SCAT were evaluated using in situ microdialysis. Infusion of octreotide suppressed plasma insulin and growth hormone levels at rest and during exercise. It blocked the exercise-induced increase in plasma adrenaline while that of noradrenaline was unchanged. Plasma natriuretic peptides (NPs) level was higher at rest and during exercise under octreotide infusion in lean men. Under placebo, no difference was found in the exercise-induced increase in glycerol between the probe perfused with Ringer solution alone and that with phentolamine (an alpha-adrenergic receptor antagonist) in lean subjects while a greater increase in glycerol was observed in the obese subjects. Under placebo, propranolol infusion in the probe containing phentolamine reduced by about 45% exercise-induced glycerol release; this effect was fully suppressed under octreotide infusion while noradrenaline was still elevated and exercise-induced lipid mobilization maintained in both lean and obese individuals. In conclusion, blockade of beta-adrenergic receptors during exercise performed during infusion of octreotide (blocking the exercise-induced rise in adrenaline but not that of noradrenaline) does not alter the exercise-induced lipolysis. This suggests that adrenaline is the main adrenergic agent contributing to exercise-induced lipolysis in SCAT. Moreover, it is the combined action of insulin suppression and NPs release which explains the lipolytic response which remains under octreotide after full local blockade of fat cell adrenergic receptors. For the moment, it is unknown if results apply specifically to SCAT and exercise only or if conclusions could be extended to all forms of lipolysis in humans. PMID:19417097

de Glisezinski, I; Larrouy, D; Bajzova, M; Koppo, K; Polak, J; Berlan, M; Bulow, J; Langin, D; Marques, M A; Crampes, F; Lafontan, M; Stich, V

2009-05-05

376

Alteration of the copy number and deletion of mitochondrial DNA in human hepatocellular carcinoma  

Microsoft Academic Search

Somatic mutations in mitochondrial DNA (mtDNA) have been detected in hepatocellular carcinoma (HCC). However, it remains unclear whether mtDNA copy number and mitochondrial biogenesis are altered in HCC. In this study, we found that mtDNA copy number and the content of mitochondrial respiratory proteins were reduced in HCCs as compared with the corresponding non-tumorous livers. MtDNA copy number was significantly

P H Yin; H C Lee; G Y Chau; Y T Wu; S H Li; W Y Lui; Y H Wei; T Y Liu; C W Chi

2004-01-01

377

Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease  

PubMed Central

The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia.

Waltz, Xavier; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Machado, Roberto F.; Lamarre, Yann; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Tressieres, Benoit; Divialle-Doumdo, Lydia; Petras, Marie; Maillard, Frederic; Etienne-Julan, Maryse; Connes, Philippe

2013-01-01

378

Acute and chronic watercress supplementation attenuates exercise-induced peripheral mononuclear cell DNA damage and lipid peroxidation.  

PubMed

Pharmacological antioxidant vitamins have previously been investigated for a prophylactic effect against exercise-induced oxidative stress. However, large doses are often required and may lead to a state of pro-oxidation and oxidative damage. Watercress contains an array of nutritional compounds such as ?-carotene and ?-tocopherol which may increase protection against exercise-induced oxidative stress. The present randomised controlled investigation was designed to test the hypothesis that acute (consumption 2 h before exercise) and chronic (8 weeks consumption) watercress supplementation can attenuate exercise-induced oxidative stress. A total of ten apparently healthy male subjects (age 23 (SD 4) years, stature 179 (SD 10) cm and body mass 74 (SD 15) kg) were recruited to complete the 8-week chronic watercress intervention period (and then 8 weeks of control, with no ingestion) of the experiment before crossing over in order to compete the single-dose acute phase (with control, no ingestion). Blood samples were taken at baseline (pre-supplementation), at rest (pre-exercise) and following exercise. Each subject completed an incremental exercise test to volitional exhaustion following chronic and acute watercress supplementation or control. The main findings show an exercise-induced increase in DNA damage and lipid peroxidation over both acute and chronic control supplementation phases (P< 0.05 v. supplementation), while acute and chronic watercress attenuated DNA damage and lipid peroxidation and decreased H?O? accumulation following exhaustive exercise (P< 0.05 v. control). A marked increase in the main lipid-soluble antioxidants (?-tocopherol, ?-tocopherol and xanthophyll) was observed following watercress supplementation (P< 0.05 v. control) in both experimental phases. These findings suggest that short- and long-term watercress ingestion has potential antioxidant effects against exercise-induced DNA damage and lipid peroxidation. PMID:22475430

Fogarty, Mark C; Hughes, Ciara M; Burke, George; Brown, John C; Davison, Gareth W

2012-04-05

379

Hematologic and hemorheological determinants of resting and exercise-induced hemoglobin oxygen desaturation in children with sickle cell disease.  

PubMed

The aim of the study was to determine the factors associated with resting and exercise-induced hemoglobin oxygen desaturation. The well-established six-minute walk test was conducted in 107 sickle cell children (50 with sickle hemoglobin C disease and 57 with sickle cell anemia) at steady state. Hemoglobin oxygen saturation was measured before and immediately after the six-minute walk test. Blood samples were obtained on the same day to measure hematologic and hemorheological parameters. Exercise-induced hemoglobin oxygen desaturation was defined as a drop in hemoglobin oxygen saturation of 3% or more at the end of the six-minute walk test compared to resting levels. No children with sickle hemoglobin C disease, but approximately 50% of children with sickle cell anemia showed mild or moderate oxygen desaturation at rest, which was independently associated with the percentage of reticulocytes. Exercise-induced hemoglobin oxygen desaturation was observed in 18% of children with sickle hemoglobin C disease and 34% of children with sickle cell anemia, and was independently associated with the six-minute walk test, acute chest syndrome rate and the strength of red blood cell aggregates in children with sickle cell anemia. No association was found in children with sickle hemoglobin C disease between exercise-induced hemoglobin oxygen desaturation and the measured parameters. Hemoglobin oxygen desaturation at rest was common in children with sickle cell anemia but not in children with sickle hemoglobin C disease, and was mainly associated with greater hemolysis. Physiological strain during exercise and red blood cell aggregation properties may predict the occurrence of exercise-induced hemoglobin oxygen desaturation in children with sickle cell anemia. PMID:23539539

Waltz, Xavier; Romana, Marc; Lalanne-Mistrih, Marie-Laure; Machado, Roberto F; Lamarre, Yann; Tarer, Vanessa; Hardy-Dessources, Marie-Dominique; Tressières, Benoît; Divialle-Doumdo, Lydia; Petras, Marie; Maillard, Frederic; Etienne-Julan, Maryse; Connes, Philippe

2013-03-28

380

Mitochondrial abnormalities in temporal lobe of autistic brain.  

PubMed

Autism spectrum disorder (ASD) consists of a group of complex developmental disabilities characterized by impaired social interactions, deficits in communication and repetitive behavior. Multiple lines of evidence implicate mitochondrial dysfunction in ASD. In postmortem BA21 temporal cortex, a region that exhibits synaptic pathology in ASD, we found that compared to controls, ASD patients exhibited altered protein levels of mitochondria respiratory chain protein complexes, decreased Complex I and IV activities, decreased mitochondrial antioxidant enzyme SOD2, and greater oxidative DNA damage. Mitochondrial membrane mass was higher in ASD brain, as indicated by higher protein levels of mitochondrial membrane proteins Tom20, Tim23 and porin. No differences were observed in either mitochondrial DNA or levels of the mitochondrial gene transcription factor TFAM or cofactor PGC1?, indicating that a mechanism other than alterations in mitochondrial genome or mitochondrial biogenesis underlies these mitochondrial abnormalities. We further identified higher levels of the mitochondrial fission proteins (Fis1 and Drp1) and decreased levels of the fusion proteins (Mfn1, Mfn2 and Opa1) in ASD patients, indicating altered mitochondrial dynamics in ASD brain. Many of these changes were evident in cortical pyramidal neurons, and were observed in ASD children but were less pronounced or absent in adult patients. Together, these findings provide evidence that mitochondrial function and intracellular redox status are compromised in pyramidal neurons in ASD brain and that mitochondrial dysfunction occurs during early childhood when ASD symptoms appear. PMID:23333625

Tang, Guomei; Gutierrez Rios, Puri; Kuo, Sheng-Han; Akman, Hasan Orhan; Rosoklija, Gorazd; Tanji, Kurenai; Dwork, Andrew; Schon, Eric A; Dimauro, Salvatore; Goldman, James; Sulzer, David

2013-01-17

381

Mitochondrial RNA processing in trypanosomes  

PubMed Central

The mitochondrial genome of trypanosomes is composed of ~50 maxicircles and thousands of minicircles. Maxi- (~25 kb) and mini-(~1 kb)circles are catenated and packed into a dense structure called a kinetoplast. Both types of circular DNA are transcribed by a phage-like RNA polymerase: maxicircles yield multicistronic rRNA and mRNA precursors, while guide RNA (gRNA) precursors are produced from minicircles. To function in mitochondrial translation, pre-mRNAs must undergo a nucleolytic processing and 3? modifications, and often uridine insertion/deletion editing. gRNAs, which represent short (50-60 nt) RNAs directing editing reactions, are produced by 3? nucleolytic processing of a much longer precursor followed by 3? uridylation. Ribosomal RNAs are excised from precursors and their 3? ends are also trimmed and uridylated. All tRNAs are imported from the cytoplasm and some are further modified and edited in the mitochondrial matrix. Historically, the fascinating phenomenon of RNA editing has been extensively studied as an isolated pathway in which nuclear-encoded proteins mediate interactions of maxi- and minicircle transcripts to create open reading frames. However, recent studies unraveled a highly integrated network of mitochondrial genome expression including critical pre- and postediting 3? mRNA processing, and gRNA and rRNA maturation steps. Here we focus on RNA 3? adenylation and uridylation as processes essential for biogenesis, stability and functioning of mitochondrial RNAs.

Aphasizhev, Ruslan; Aphasizheva, Inna

2011-01-01

382

High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial  

PubMed Central

Background Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced energy deficit effects on glucose metabolism are mitigated by increased dietary protein. Methods Nineteen men ([mean ± SD] 23 ± 2 y, VO2peak 59 ± 5 ml·kg-1·min-1) were divided into three groups, two consuming moderate (MP; 0.9 g protein kg-1 d-1), and one high (HP; 1.8 g protein kg-1 d-1) protein diets (55% energy from carbohydrate) for 11 days. Following 4 days of energy balance (D1-4), energy expenditure was increased for 7 days (D5-12) in all groups. Energy intake was unchanged in two, creating a 1000 kcal d-1 deficit (DEF-MP, DEF-HP; n = 6, both groups), whereas energy balance was maintained in the third (BAL-MP, n = 7). Biochemical markers of substrate metabolism were measured during fasting rest on D4 and D12, as were GP and contribution of gluconeogenesis to endogenous glucose production (fgng) using 4-h primed, continuous infusions of [6,6-2H2]glucose (dilution-method) and [2-13C]glycerol (MIDA technique). Glycogen breakdown (GB) was derived from GP and fgng. Results Plasma ?-hydroxybutyrate levels increased, and plasma glucose and insulin declined from D4 to D12, regardless of group. DEF-MP experienced decreased plasma GP from D4 to D12 ([mean change ± SD] 0.24 ± 0.24 mg·kg-1·min-1), due to reduced GB from D4 (1.40 ± 0.28 mg·kg-1·min-1) to D12 (1.16 ± 0.17 mg·kg-1·min-1), P < 0.05. Conversely, BAL-MP and DEF-HP sustained GP from D4 to D12 ([mean change ± SD] 0.1 ± 0.5 and 0.0 ± 0.2 mg·kg-1·min-1, respectively) by maintaining GB. Conclusion Exercise-induced energy deficit decreased GP and additional dietary protein mitigated that effect.

2011-01-01

383

Mitochondrial Medicine  

Microsoft Academic Search

Mitochondrial medicine represents a complex of clinical, biochemical, pathological and genetic information crucial in diagnosis\\u000a and treatment. An outline of the development of mitochondrial medicine was for the first time published by Luft in 1994 [22].\\u000a Several organizations are focused on mitochondrial medicine, from experimental and clinical research (Mitochondrial Research\\u000a Society – MRS) to patients application (Mitochondrial Medicine Society –MMS),

Anna Gvozdjáková

384

Enantiomeric Natural Products: Occurrence and Biogenesis**  

PubMed Central

In Nature, chiral natural products are usually produced in optically pure form; however, on occasion Nature is known to produce enantiomerically opposite metabolites. These enantiomeric natural products can arise in Nature from a single species, or from different genera and/or species. Extensive research has been carried out over the years in an attempt to understand the biogenesis of naturally occurring enantiomers, however, many fascinating puzzles and stereochemical anomalies still remain.

Finefield, Jennifer M.; Sherman, David H.; Kreitman, Martin; Williams, Robert M.

2012-01-01

385

Mouse models for peroxisome biogenesis disorders  

Microsoft Academic Search

The gene knockout technology has been applied to generate mice lacking functional peroxisomes. These mice are a model for\\u000a Zellweger syndrome and other peroxisome biogenesis disorders that are lethal in early life. Extensive biochemical, ultrastructural,\\u000a and neurodevelopmental analyses indicate that the peroxisome deficient mice closely mimic the pathology in Zellweger patients\\u000a and will be a very useful tool to elucidate

Myriam Baes

2000-01-01

386

Lack of IL6 production during exercise in patients with mitochondrial myopathy  

Microsoft Academic Search

In the present study we investigated the possibility that exercise-induced increases in plasma levels of interleukin (IL)-6\\u000a are associated with plasma lactate levels. Patients with mitochondrial myopathy (MM) are characterised by high levels of plasma\\u000a lactate. In this study, seven patients with MM underwent an ergometer cycle test for 25 min without treatment. They were then\\u000a treated with dichloroacetate (DCA)

Adam Steensberg; John Vissing; Bente Klarlund Pedersen

2001-01-01

387

Prefrontal lactate predicts exercise-induced cognitive dysfunction in Gulf War Illness  

PubMed Central

Background: 25% to 30% of Veterans deployed to the 1990 to 1991 Persian Gulf War exhibit an idiopathic syndrome of chronic fatigue, exertional exhaustion, pain, hyperalgesia, cognitive and affective dysfunction known as Gulf War Illness (GWI). Methods: Gulf War veterans (n=15) and sedentary veteran and civilian controls (n=11) completed a 2-back working memory test in an fMRI before and after two bicycle exercise stress test. We performed single voxel 1H MRS to evaluate brain metabolic differences in the left anterior cingulate cortex and the changes associated with exercise. Results: Eight GWI subjects increased their 2-back scores after exercise (labelled increasers) and seven GWI subjects decreased their 2-back scores after exercise (labelled decreasers). These phenotypic responses were absent for controls. Decreasers had significantly elevated prefrontal lactate levels compared to Increasers prior to completion of the exercise stress tests. Evaluation of prefrontal lactate levels prior to exercise demonstrated predictability (ROC analysis) of the two diametrically opposed subgroups. Conclusion: Prefrontal lactate levels may be a potential biomarker for exercise-induced subgroups in GWI. The alterations in brain energetics may be in part responsible for a subgroup of GWI and underlie some of the symptoms present in the patient population.

Rayhan, Rakib U; Raksit, Megna P; Timbol, Christian R; Adewuyi, Oluwatoyin; VanMeter, John W; Baraniuk, James N

2013-01-01

388

Exercise-induced hemolysis in xerocytosis. Erythrocyte dehydration and shear sensitivity.  

PubMed Central

A patient with xerocytosis was found to have swimming-induced intravascular hemolysis and shortening of erythrocyte life-span. In a microviscometer, xerocytes were more susceptible than normal erythrocytes to hemolysis by shear stress. Fractionation of normal and abnormal cells on discontinuous Stractan density gradients revealed that increasingly dehydrated cells were increasingly more shear sensitive. This sensitivity was partially corrected by rehydrating xerocytic erythrocytes by means of the cation-ionophore nystatin in a high potassium buffer. Conversely, normal erythrocytes were rendered shear sensitive by dehydrating them with nystatin in a low potassium buffer. This effect of dehydration was entirely reversible if normal cells were dehydrated for less than 4 h but was only partially reversed after more prolonged dehydration. It is likely that dehydration of erythrocytes results in shear sensitivity primarily because of concentration of cell contents and reduced cellular deformability. With prolonged dehydration, secondary membrane changes may potentiate the primary effect. This increased shear sensitivity of dehydrated cells may explain atraumatic exercise-induced hemolysis in xerocytosis as cardiac output is shifted to vessels of exercising muscles with small diameters and high shear rates.

Platt, O S; Lux, S E; Nathan, D G

1981-01-01

389

Pulmonary inflammation due to exercise-induced pulmonary haemorrhage in Thoroughbred colts during race training.  

PubMed

This study investigated the putative roles of inflammation and platelet-activating factor (PAF) in exercise-induced pulmonary haemorrhage (EIPH). Two-year-old Thoroughbred colts (n=37) were exercised on a racetrack for 5months before commencement of the study. Each colt was then exercised at 15-16m/s over 800-1000m and broncho-alveolar lavage fluid (BALF) was collected 24h later. The colts were subsequently divided into two groups on the basis of BALF analysis; an EIPH-positive group (presence of haemosiderophages, n=23) and an EIPH-negative group (absence of haemosiderophages, n=14). BALF from the EIPH-positive group had a significantly higher protein concentration (0.39±0.28 vs. 0.19±0.12mg/mL, P=0.031), higher PAF bioactivity (0.18±0.12 vs. 0.043±0.05 340:380nm ratio, P=0.042) and a higher lipid hydroperoxide concentration compared to the EIPH-negative group. There was also a lower nitrite concentration and reduced production of superoxide anion and hydrogen peroxide by alveolar macrophages in the EIPH-positive group. There was evidence of pulmonary inflammation and a decreased innate immune response of alveolar macrophages in EIPH-positive colts compared with the EIPH-negative group. PMID:22108190

Michelotto, Pedro V; Muehlmann, Luis A; Zanatta, Ana L; Bieberbach, Eloyse W R; Kryczyk, Marcelo; Fernandes, Luis C; Nishiyama, Anita

2011-11-01

390

Contrast Water Therapy and Exercise Induced Muscle Damage: A Systematic Review and Meta-Analysis  

PubMed Central

The aim of this systematic review was to examine the effect of Contrast Water Therapy (CWT) on recovery following exercise induced muscle damage. Controlled trials were identified from computerized literature searching and citation tracking performed up to February 2013. Eighteen trials met the inclusion criteria; all had a high risk of bias. Pooled data from 13 studies showed that CWT resulted in significantly greater improvements in muscle soreness at the five follow-up time points (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Pooled data also showed that CWT significantly reduced muscle strength loss at each follow-up time (<6, 24, 48, 72 and 96 hours) in comparison to passive recovery. Despite comparing CWT to a large number of other recovery interventions, including cold water immersion, warm water immersion, compression, active recovery and stretching, there was little evidence for a superior treatment intervention. The current evidence base shows that CWT is superior to using passive recovery or rest after exercise; the magnitudes of these effects may be most relevant to an elite sporting population. There seems to be little difference in recovery outcome between CWT and other popular recovery interventions.

Bieuzen, Francois; Bleakley, Chris M.; Costello, Joseph Thomas

2013-01-01

391

IL-6 is not essential for exercise-induced increases in glucose uptake.  

PubMed

Interleukin-6 (IL-6) increases glucose uptake in resting skeletal muscle. IL-6 is released from skeletal muscle during exercise; however; it is not known whether this IL-6 response is important for exercise-induced increases in skeletal muscle glucose uptake. We report that IL-6 knockout (KO) mice, 4 mo of age, have similar body weight to wild-type (WT), and, under resting conditions, oxygen consumption, food intake, substrate utilization, glucose tolerance, and insulin sensitivity are not different. Maximal exercise capacity is also similar to WT. We investigated substrate utilization and glucose clearance in vivo during steady-state treadmill running at 70% of maximal running speed and found that WT and IL-6 KO mice had similar rates of substrate utilization, muscle glucose clearance, and phosphorylation of AMP-activated protein kinase T172. These data provide evidence that IL-6 does not play a major role in regulating substrate utilization or skeletal muscle glucose uptake during steady-state endurance exercise. PMID:23449935

O'Neill, Hayley M; Palanivel, Rengasamy; Wright, David C; MacDonald, Tara; Lally, James S; Schertzer, Jonathan D; Steinberg, Gregory R

2013-02-28

392

Underweight and overweight men have greater exercise-induced dyspnoea than normal weight men  

PubMed Central

Introduction. Persons with high or low body mass index (BMI), involved in clinical or mechanistic trials involving exercise testing, might estimate dyspnoea differently from persons with a normal BMI. Aims. Our objective was to investigate the relationship between BMI and dyspnoea during exercise in normal subjects with varying BMI. Material and methods. A total of 37 subjects undertook progressive exercise testing. Subjects were divided into three groups: underweight (UW), normal weight (NW), and overweight (OW). Dyspnoea was estimated using the visual analogue scale (VAS). Spirometry, maximum voluntary ventilation (MVV), and respiratory muscle strength (RMS) were measured. Results and discussion. The intercept of the VAS/ventilation relationship was significantly higher in NW subjects compared to UW (P = 0.029) and OW subjects (P = 0.040). Relative to the OW group, FVC (P = 0.020), FEV1 (P = 0.024), MVV (P = 0.019), and RMS (P = 0.003) were significantly decreased in the UW group. The greater levels of dyspnoea in UW subjects could possibly be due to decreased RMS. Healthy persons should aim to achieve an optimum BMI range to have the lowest exercise-induced dyspnoea.

Ali, Syed a.; Bokhari, Syed S. I.; Khan, Mohammed n.; Ahmad, Hakimuddin r.

2012-01-01

393

Exercise-induced hyperkalaemia: effects of beta-adrenoceptor blocker vs diuretic.  

PubMed Central

Four groups of eight normotensive male volunteers performed a 60 min bicycle exercise test before and after 2 weeks of either placebo, hydrochlorothiazide (HCTZ, 25 mg day-1), pindolol (PIND, 10 mg day-1) or both drugs in combination using a double-blind, randomized design. During exercise on placebo serum potassium increased by 0.8 mmol l-1. HCTZ significantly decreased potassium levels at rest and during exercise by 0.2 mmol l-1. PIND did not affect resting potassium levels but potentiated the increase by 0.4 mmol l-1 at the end of exercise, and delayed the return to normal of serum potassium after exercise. The addition of HCTZ to PIND offset the potentiating effect of PIND on exercise-induced hyperkalaemia (only after prolonged exercise) and accelerated the return to baseline after exercise. The results indicate that the hypokalaemic effect of HCTZ can oppose the hyperkalaemic effect of PIND during prolonged physical exercise and particularly during recovery.

Cleroux, J; Peterson, M; Leenen, F H

1987-01-01

394

Exercise-induced hypertension among healthy firefighters-a comparison between two different definitions.  

PubMed

Different studies have yielded conflicting results regarding the association of hypertensive response to exercise and cardiovascular morbidity. We compared two different definitions of exaggerated hypertensive response to exercise and their association with cardio-respiratory fitness in a population of healthy firefighters. We examined blood pressure response to exercise in 720 normotensive male career firefighters. Fitness was measured as peak metabolic equivalent tasks (METs) achieved during maximal exercise treadmill tests. Abnormal hypertensive response was defined either as systolic blood pressure ? 200 mm Hg; or alternatively, as responses falling in the upper tertile of blood pressure change from rest to exertion, divided by the maximal workload achieved. Using the simple definition of a 200 mm Hg cutoff at peak exercise less fit individuals (METs ? 12) were protected from an exaggerated hypertensive response (OR 0.45, 95%CI 0.30-0.67). However, using the definition of exercise-induced hypertension that corrects for maximal workload, less fit firefighters had almost twice the risk (OR 1.8, 95%CI 1.3-2.47). Blood pressure change corrected for maximal workload is better correlated with cardiorespiratory fitness. Systolic blood pressure elevation during peak exercise likely represents an adaptive response, whereas elevation out of proportion to the maximal workload may indicate insufficient vasodilation and a maladaptive response. Prospective studies are needed to best define exaggerated blood pressure response to exercise. PMID:23246464

Leiba, Adi; Baur, Dorothee M; Kales, Stefanos N

2012-12-14

395

Posterior reversible encephalopathy syndrome with exercise-induced acute kidney injury in renal hypouricemia type 1.  

PubMed

Renal hypouricemia type 1 is caused by mutations in the SLC22A12 gene, whereas type 2 is caused by defects in the SLC2A9 gene. Although both subtypes predispose to exercise-induced acute kidney injury (EIAKI), posterior reversible encephalopathy syndrome (PRES) occurring with this disorder is an uncommon phenomenon that has only been reported to date in a patient with renal hypouricemia type 2. We describe a 13-year-old boy with renal hypouricemia type 1 (serum uric acid, 0.9 mg/dL) with a homozygous W258X mutation in the SLC22A12 gene, presenting with EIAKI and PRES. On admission, his body weight was 61 kg (11 kg above the dry weight), and blood pressure was 153/88 mmHg. Cranial magnetic resonance imaging revealed high-intensity areas in the cortical and subcortical white matter of the occipital lobe. After admission, the patient responded well to a combination of hemodialysis and intravenous nicardipine. This is the first case of concurrent PRES and EIAKI in a patient with renal hypouricemia type 1. We suggest that PRES is not due to severe hypouricemia caused by SLC2A9 mutation but is a manifestation of severe EIAKI associated with renal hypouricemia. PMID:23525542

Fujinaga, Shuichiro; Ito, Akira; Nakagawa, Mayu; Watanabe, Tsuneki; Ohtomo, Yoshiyuki; Shimizu, Toshiaki

2013-03-23

396

Exercise-induced inflammatory reaction affects electromyographic changes in skeletal muscle during dynamic contractions in humans.  

PubMed

In order to assess the role of exercise-induced inflammatory reactions on electromyographic (EMG) changes in humans, we have recorded, during a 3-min dynamic handgrip exercise at a high strength (112 w), the surface EMG and the compound evoked muscle action potential (M-wave) in control conditions, and this after ingestion of a well known cyclooxygenase blocker i.e. acetylsalicylic acid (ASA), either as a single dose treatment (10 mg/kg) and as a 3-day treatment (30 mg/kg per day). The power spectrum density function of EMG allowed us to compute both the median frequency (MF) and the energies in a low- and