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1

Regulation of mitochondrial biogenesis  

PubMed Central

Although it is well established that physical activity increases mitochondrial content in muscle, the molecular mechanisms underlying this process have only recently been elucidated. Mitochondrial dysfunction is an important component of different diseases associated with aging, such as Type 2 diabetes and Alzheimer’s disease. PGC-1? (peroxisome-proliferator-activated receptor ? co-activator-1?) is a co-transcriptional regulation factor that induces mitochondrial biogenesis by activating different transcription factors, including nuclear respiratory factor 1 and nuclear respiratory factor 2, which activate mitochondrial transcription factor A. The latter drives transcription and replication of mitochondrial DNA. PGC-1? itself is regulated by several different key factors involved in mitochondrial biogenesis, which will be reviewed in this chapter. Of those, AMPK (AMP-activated protein kinase) is of major importance. AMPK acts as an energy sensor of the cell and works as a key regulator of mitochondrial biogenesis. AMPK activity has been shown to decrease with age, which may contribute to decreased mitochondrial biogenesis and function with aging. Given the potentially important role of mitochondrial dysfunction in the pathogenesis of numerous diseases and in the process of aging, understanding the molecular mechanisms regulating mitochondrial biogenesis and function may provide potentially important novel therapeutic targets. PMID:20533901

Jornayvaz, Francois R.; Shulman, Gerald I.

2013-01-01

2

MYC and mitochondrial biogenesis.  

PubMed

Mitochondria, the powerhouses of the cell, face two imperatives concerning biogenesis. The first is the requirement for dividing cells to replicate their mitochondrial content by growth of existing mitochondria. The second is the dynamic regulation of mitochondrial content in response to organismal and cellular cues (e.g., exercise, caloric restriction, energy status, temperature). MYC provides the clearest example of a programmed expansion of mitochondrial content linked to the cell cycle. As an oncogene, MYC also presents intriguing questions about the role of its mitochondrial targets in cancer-related phenotypes, such as the Warburg effect and MYC-dependent apoptosis. PMID:24789872

Morrish, Fionnuala; Hockenbery, David

2014-05-01

3

Editorial: mitochondrial biogenesis: pharmacological approaches.  

PubMed

Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS), myoclonic epilepsy with ragged-red fibers (MERRF), mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), Leber's hereditary optic neuropathy (LHON), the syndrome of neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP), and Leigh's syndrome. Likewise, other diseases in which mitochondrial dysfunction plays a very important role include neurodegenerative diseases, diabetes or cancer. Generally, in mitochondrial diseases a mutation in the mitochondrial DNA leads to a loss of functionality of the OXPHOS system and thus to a depletion of ATP and overproduction of ROS, which can, in turn, induce further mtDNA mutations. The work by Yu-Ting Wu, Shi-Bei Wu, and Yau-Huei Wei (Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taiwan) [4] focuses on the aforementioned mitochondrial diseases with special attention to the compensatory mechanisms that prompt mitochondria to produce more energy even under mitochondrial defect-conditions. These compensatory mechanisms include the overexpression of antioxidant enzymes, mitochondrial biogenesis and overexpression of respiratory complex subunits, as well as metabolic shift to glycolysis. The pathways observed to be related to mitochondrial biogenesis as a compensatory adaptation to the energetic deficits in mitochondrial diseases are described (PGC- 1, Sirtuins, AMPK). Several pharmacological strategies to trigger these signaling cascades, according to these authors, are the use of bezafibrate to activate the PPAR-PGC-1? axis, the activation of AMPK by resveratrol and the use of Sirt1 agonists such as quercetin or resveratrol. Other strategies currently used include the addition of antioxidant supplements to the diet (dietary supplementation with antioxidants) such as L-carnitine, coenzyme Q10,MitoQ10 and other mitochondria-targeted antioxidants,N-acetylcysteine (NAC), vitamin C, vitamin E vitamin K1, vitamin B, sodium pyruvate or -lipoic acid. As aforementioned, other diseases do not have exclusively a mitochondrial origin but they might have an importan

Valero, Teresa

2014-01-01

4

Adiponectin is sufficient, but not required, for exercise-induced increases in the expression of skeletal muscle mitochondrial enzymes.  

PubMed

Adiponectin (Ad) has been proposed to be a regulator of mitochondrial biogenesis in skeletal muscle, and necessary for exercise-induced increases in mitochondrial content. We first confirmed that Ad could acutely increase the expression of mitochondrial proteins during a 10 h incubation in isolated soleus and extensor digitorum longus (EDL) muscles. Next, we further examined the role of Ad as a regulator of mitochondrial content using Ad knockout (AdKO) mice. The AdKO animals showed no differences in resting VO2, respiratory exchange ratio, or in time to exhaustion during exercise when compared to wild-type (WT) mice. There was a reduction in resting palmitate oxidation in isolated soleus from AdKO animals (-23%, P < 0.05) but not EDL, and 5-aminoimidazole-4-carboxamide (AICAR)-stimulated palmitate oxidation was similar in both genotypes regardless of muscle. There were no differences in protein markers of mitochondrial content (COX4, CORE1, CS, PDHE1?) in red and white gastrocnemius between WT and AdKO animals. A single bout of treadmill running increased the phosphorylation of AMP-activated protein kinase (AMPK) and the mRNA expression of mitochondrial proteins in red and white gastrocnemius in both WT and AdKO animals, with no differences between genotypes. Finally, 8 weeks of chronic exercise training increased the protein content of mitochondrial markers similarly (?25-35%) in red gastrocnemius from both WT and AdKO mice. Collectively, our results demonstrate that the absence of Ad is not accompanied by reductions in mitochondrial protein content, or a reduction in aerobic exercise capacity. We conclude that Ad is not required for the maintenance of mitochondrial content, or for exercise-induced increases in skeletal muscle mitochondrial proteins. PMID:24687585

Ritchie, Ian R W; MacDonald, Tara L; Wright, David C; Dyck, David J

2014-06-15

5

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

2012-12-01

6

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. PMID:22303236

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

2008-01-01

7

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

8

Reperfusion Promotes Mitochondrial Biogenesis following Focal Cerebral Ischemia in Rats  

PubMed Central

Background and Purpose Reperfusion after transient cerebral ischemia causes severe damage to mitochondria; however, little is known regarding the continuous change in mitochondrial biogenesis during reperfusion. Mitochondrial biogenesis causes an increase in the individual mitochondrial mass of neurons and maintains their aerobic set-point in the face of declining function. The aim of this study was to examine mitochondrial biogenesis in the cortex during reperfusion following focal cerebral ischemia. Methods Male Wistar rats were subjected to transient focal cerebral ischemia. The relative amount of cortical mitochondrial DNA was analyzed using quantitative real-time PCR at 0 h, 24 h, 72 h, and 7 d after reperfusion. Three critical transcriptional regulators of mitochondrial biogenesis were measured by semi-quantitative reverse-transcription PCR. The protein expression of cytochrome C oxidase subunits I and IV was detected by Western blotting. Results Evidence of increased mitochondrial biogenesis was observed after reperfusion. The cortical mitochondrial DNA content increased after 24 h, peaked after 72 h, and maintained a high level for 7 d. The cortical expression of three critical genes for the transcriptional regulation of mitochondrial biogenesis, namely, peroxisome proliferator-activated receptor coactivator-1?, nuclear respiratory factor-1, and mitochondrial transcription factor A, also increased at 24 h and 72 h. The expression of peroxisome proliferator-activated receptor coactivator-1? returned to the baseline level at 7 d, but two other factors maintained higher levels compared with the controls. Moreover, the expression of cytochrome C oxidase subunits I and IV was increased in the cortex. Conclusions These results indicate that reperfusion increased mitochondrial biogenesis following focal cerebral ischemia, and this tendency was exacerbated as the reperfusion time was extended. Reperfusion-induced mitochondrial biogenesis was mediated through up-regulation of critical transcriptional regulators of mitochondrial biogenesis. PMID:24667167

Xie, Yuying; Li, Jun; Fan, Guibo; Qi, Sihua; Li, Bing

2014-01-01

9

Divergent Mitochondrial Biogenesis Responses in Human Cardiomyopathy  

PubMed Central

Background Mitochondria are key players in the development and progression of heart failure (HF). Mitochondrial (mt) dysfunction leads to diminished energy production and increased cell death contributing to the progression of left ventricular (LV) failure. The fundamental mechanisms that underlie mt dysfunction in HF have not been fully elucidated. Methods and Results To characterize mt morphology, biogenesis and genomic integrity in human HF, we investigated LV tissue from non-failing (NF) hearts and end-stage ischemic (ICM) or dilated (DCM) cardiomyopathic hearts. Although mt dysfunction was present in both types of cardiomyopathy, mt were smaller and increased in number in DCM compared to ICM or NF hearts. Mt volume density and mtDNA copy number was increased by ~2-fold (P<0.001) in DCM hearts in comparison to ICM hearts. These changes were accompanied by an increase in the expression of mtDNA-encoded genes in DCM versus no change in ICM. mtDNA repair and antioxidant genes were reduced in failing hearts suggestive of a defective repair and protection system, which may account for the 4.1-fold increase in mtDNA deletion mutations in DCM (P<0.05 vs NF hearts, P<0.05 vs ICM). Conclusions In DCM, mt dysfunction is associated with mtDNA damage and deletions, which could be a consequence of mutating stress coupled with a PGC-1?-dependent stimulus for mt biogenesis. However, this maladaptive compensatory response contributes to additional oxidative damage. Thus, our findings support further investigations into novel mechanisms and therapeutic strategies for mt dysfunction in DCM. PMID:23589024

Ahuja, Preeti; Wanagat, Jonathan; Wang, Zhihua; Wang, Yibin; Liem, David A.; Ping, Peipei; Antoshechkin, Igor A.; Margulies, Kenneth B.; MacLellan, W. Robb

2014-01-01

10

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

11

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. PMID:21757760

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

12

Chronic Caloric Restriction Preserves Mitochondrial Function in Senescence Without Increasing Mitochondrial Biogenesis  

PubMed Central

SUMMARY Caloric restriction (CR) mitigates many detrimental effects of aging and prolongs lifespan. CR has been suggested to increase mitochondrial biogenesis, thereby attenuating age-related declines in mitochondrial function; a concept that is challenged by recent studies. Here we show that lifelong CR in mice prevents age-related loss of mitochondrial oxidative capacity and efficiency, measured in isolated mitochondria and permeabilized muscle fibers. We find that these beneficial effects of CR occur without increasing mitochondrial abundance. Whole-genome expression profiling and large-scale proteomic surveys revealed expression patterns inconsistent with increased mitochondrial biogenesis, which is further supported by lower mitochondrial protein synthesis with CR. We find that CR decreases oxidant emission, increases antioxidant scavenging, and minimizes oxidative damage to DNA and protein. These results demonstrate that CR preserves mitochondrial function by protecting the integrity and function of existing cellular components rather than by increasing mitochondrial biogenesis. PMID:23217257

Lanza, Ian R.; Zabielski, Piotrek; Klaus, Katherine A.; Morse, Dawn M.; Heppelmann, Carrie J.; Bergen, H. Robert; Dasari, Surendra; Walrand, Stephane; Short, Kevin R.; Johnson, Matthew L.; Robinson, Matthew M.; Schimke, Jill M.; Jakaitis, Daniel R.; Asmann, Yan W.; Sun, Zhifu; Nair, K. Sreekumaran

2012-01-01

13

Echinochrome a increases mitochondrial mass and function by modulating mitochondrial biogenesis regulatory genes.  

PubMed

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1?, estrogen-related receptor (ERR)-?, peroxisome proliferator-activator receptor (PPAR)-?, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis. PMID:25196935

Jeong, Seung Hun; Kim, Hyoung Kyu; Song, In-Sung; Noh, Su Jin; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Mishchenko, Natalia P; Fedoreyev, Sergey A; Stonik, Valentin A; Han, Jin

2014-08-01

14

Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease  

Microsoft Academic Search

The metabolic syndrome is a constellation of metabolic disorders including obesity, hypertension, and insulin resistance,\\u000a components which are risk factors for the development of diabetes, hypertension, cardiovascular, and renal disease. Pathophysiological\\u000a abnormalities that contribute to the development of the metabolic syndrome include impaired mitochondrial oxidative phosphorylation\\u000a and mitochondrial biogenesis, dampened insulin metabolic signaling, endothelial dysfunction, and associated myocardial functional\\u000a abnormalities.

Jun Ren; Lakshmi Pulakat; Adam Whaley-Connell; James R. Sowers

2010-01-01

15

Extracellular growth factors and mitogens cooperate to drive mitochondrial biogenesis.  

PubMed

Cells generate new organelles when stimulated by extracellular factors to grow and divide; however, little is known about how growth and mitogenic signalling pathways regulate organelle biogenesis. Using mitochondria as a model organelle, we have investigated this problem in primary Schwann cells, for which distinct factors act solely as mitogens (neuregulin) or as promoters of cell growth (insulin-like growth factor 1; IGF1). We find that neuregulin and IGF1 act synergistically to increase mitochondrial biogenesis and mitochondrial DNA replication, resulting in increased mitochondrial density in these cells. Moreover, constitutive oncogenic Ras signalling results in a further increase in mitochondrial density. This synergistic effect is seen at the global transcriptional level, requires both the ERK and phosphoinositide 3-kinase (PI3K) signalling pathways and is mediated by the transcription factor ERRalpha. Interestingly, the effect is independent of Akt-TOR signalling, a major regulator of cell growth in these cells. This separation of the pathways that drive mitochondrial biogenesis and cell growth provides a mechanism for the modulation of mitochondrial density according to the metabolic requirements of the cell. PMID:19920079

Echave, Pedro; Machado-da-Silva, Gisela; Arkell, Rebecca S; Duchen, Michael R; Jacobson, Jake; Mitter, Richard; Lloyd, Alison C

2009-12-15

16

Mitochondrial Dysregulation in the Pathogenesis of Diabetes: Potential for Mitochondrial Biogenesis-Mediated Interventions  

PubMed Central

Muscle mitochondrial metabolism is a tightly controlled process that involves the coordination of signaling pathways and factors from both the nuclear and mitochondrial genomes. Perhaps the most important pathway regulating metabolism in muscle is mitochondrial biogenesis. In response to physiological stimuli such as exercise, retrograde signaling pathways are activated that allow crosstalk between the nucleus and mitochondria, upregulating hundreds of genes and leading to higher mitochondrial content and increased oxidation of substrates. With type 2 diabetes, these processes can become dysregulated and the ability of the cell to respond to nutrient and energy fluctuations is diminished. This, coupled with reduced mitochondrial content and altered mitochondrial morphology, has been directly linked to the pathogenesis of this disease. In this paper, we will discuss our current understanding of mitochondrial dysregulation in skeletal muscle as it relates to type 2 diabetes, placing particular emphasis on the pathways of mitochondrial biogenesis and mitochondrial dynamics, and the therapeutic value of exercise and other interventions. PMID:22203837

Joseph, Anna-Maria; Joanisse, Denis R.; Baillot, Richard G.; Hood, David A.

2012-01-01

17

Folding and Biogenesis of Mitochondrial Small Tim Proteins  

PubMed Central

Correct and timely folding is critical to the function of all proteins. The importance of this is illustrated in the biogenesis of the mitochondrial intermembrane space (IMS) “small Tim” proteins. Biogenesis of the small Tim proteins is regulated by dedicated systems or pathways, beginning with synthesis in the cytosol and ending with assembly of individually folded proteins into functional complexes in the mitochondrial IMS. The process is mostly centered on regulating the redox states of the conserved cysteine residues: oxidative folding is crucial for protein function in the IMS, but oxidized (disulfide bonded) proteins cannot be imported into mitochondria. How the redox-sensitive small Tim precursor proteins are maintained in a reduced, import-competent form in the cytosol is not well understood. Recent studies suggest that zinc and the cytosolic thioredoxin system play a role in the biogenesis of these proteins. In the IMS, the mitochondrial import and assembly (MIA) pathway catalyzes both import into the IMS and oxidative folding of the small Tim proteins. Finally, assembly of the small Tim complexes is a multistep process driven by electrostatic and hydrophobic interactions; however, the chaperone function of the complex might require destabilization of these interactions to accommodate the substrate. Here, we review how folding of the small Tim proteins is regulated during their biogenesis, from maintenance of the unfolded precursors in the cytosol, to their import, oxidative folding, complex assembly and function in the IMS. PMID:23945562

Ceh-Pavia, Efrain; Spiller, Michael P.; Lu, Hui

2013-01-01

18

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis  

E-print Network

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis SIMILARITIES function together to assist in the biogenesis of iron- sulfur (Fe/S) centers in the mitochondrial matrix chaperones work to- gether, along with other proteins, in the processes of iron- sulfur center biogenesis

Craig, Elizabeth A

19

Increases in Mitochondrial Biogenesis Impair Carcinogenesis at Multiple Levels  

PubMed Central

Although mitochondrial respiration is decreased in most cancer cells, the role of this decrease in carcinogenesis and cancer progression is still unclear. To better understand this phenomenon, instead of further inhibiting mitochondrial function, we induced mitochondrial biogenesis in transformed cells by activating the peroxisome proliferator-activated receptors (PPARs)/ peroxisome proliferator-activated receptor gamma co-activator 1? (PGC-1?) pathways. This was achieved by treating the cells with bezafibrate, a PPARs panagonist that also enhances PGC-1? expression. We confirmed that bezafibrate treatment led to increased mitochondrial proteins and enzyme functions. We found that cells with increased mitochondrial biogenesis had decreased growth rates in glucose-containing medium. In addition, they became less invasive, which was directly linked to the reduced lactate levels. Surprisingly, even though bezafibrate-treated cells had higher levels of mitochondrial markers, total respiration was not significantly altered. However, respiratory coupling, and ATP levels were. Our data show that by increasing the efficiency of the mitochondrial oxidative phosphorylation system, cancer progression is hampered by decreases in cell proliferation and invasiveness. PMID:21855427

Wang, Xiao; Moraes, Carlos T.

2011-01-01

20

Sulfur dioxide inhalation stimulated mitochondrial biogenesis in rat brains.  

PubMed

Sulfur dioxide (SO(2)) is a common environmental pollutant. Mitochondria play essential roles in energy metabolism, generation of reactive oxygen species, and regulation of apoptosis in response to neuronal brain injury. It is of interest to observe the effect of SO(2) on mitochondrial function in brain. In the present study, male Wistar rats were housed in exposure chambers and treated with 3.5, 7 and 14mg/m(3) SO(2) for 4h/day for 30days, while control rats were exposed to filtered air in the same condition. Mitochondrial membrane potential (MMP) was assessed in cerebral mitochondria using the lipophilic cationic probe JC-1. The amount of ATP was measured by the luciferinluciferase method. Analyses of mitochondrial replication and transcription were performed by real time PCR. The protein levels were detected using Western blotting. Our results showed that cerebral mtDNA content was markedly increased in rats after SO(2) exposure. Paralleling the change in mtDNA content, MMP, ATP content, MDA level, CO1 & 4 and ATP6 & 8 expression, and cytochrome c oxidase activity were increased in rat cortex after SO(2) inhalation. Moreover, mitochondrial biogenesis was accompanied by increased expression of NRF1 and TFAM, whereas PGC-1? was not changed. We report for the first time increased mitochondrial biogenesis in brain of rats exposed to SO(2), which might be an adaptive response to mitochondrial depletion by oxidant damage. PMID:22677886

Qin, Guohua; Wang, Jiaoxia; Huo, Yajun; Yan, Hongxia; Jiang, Cancan; Zhou, Jianxiao; Wang, Xue; Sang, Nan

2012-10-01

21

Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes  

Microsoft Academic Search

Hydroxytyrosol (HT) in extra-virgin olive oil is considered one of the most important polyphenolic compounds responsible for the health benefits of the Mediterranean diet for lowering incidence of cardiovascular disease, the most common and most serious complication of diabetes. We propose that HT may prevent these diseases by a stimulation of mitochondrial biogenesis that leads to enhancement of mitochondrial function

Jiejie Hao; Weili Shen; Guangli Yu; Haiqun Jia; Xuesen Li; Zhihui Feng; Ying Wang; Peter Weber; Karin Wertz; Edward Sharman; Jiankang Liu

2010-01-01

22

Coordination of plant mitochondrial biogenesis: keeping pace with cellular requirements  

PubMed Central

Plant mitochondria are complex organelles that carry out numerous metabolic processes related with the generation of energy for cellular functions and the synthesis and degradation of several compounds. Mitochondria are semiautonomous and dynamic organelles changing in shape, number, and composition depending on tissue or developmental stage. The biogenesis of functional mitochondria requires the coordination of genes present both in the nucleus and the organelle. In addition, due to their central role, all processes held inside mitochondria must be finely coordinated with those in other organelles according to cellular demands. Coordination is achieved by transcriptional control of nuclear genes encoding mitochondrial proteins by specific transcription factors that recognize conserved elements in their promoter regions. In turn, the expression of most of these transcription factors is linked to developmental and environmental cues, according to the availability of nutrients, light–dark cycles, and warning signals generated in response to stress conditions. Among the signals impacting in the expression of nuclear genes, retrograde signals that originate inside mitochondria help to adjust mitochondrial biogenesis to organelle demands. Adding more complexity, several nuclear encoded proteins are dual localized to mitochondria and either chloroplasts or the nucleus. Dual targeting might establish a crosstalk between the nucleus and cell organelles to ensure a fine coordination of cellular activities. In this article, we discuss how the different levels of coordination of mitochondrial biogenesis interconnect to optimize the function of the organelle according to both internal and external demands. PMID:24409193

Welchen, Elina; Garcia, Lucila; Mansilla, Natanael; Gonzalez, Daniel H.

2014-01-01

23

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. PMID:19300474

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

24

CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.  

PubMed

Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)-binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution. PMID:25349259

Gao, Jie; Schatton, Désirée; Martinelli, Paola; Hansen, Henriette; Pla-Martin, David; Barth, Esther; Becker, Christian; Altmueller, Janine; Frommolt, Peter; Sardiello, Marco; Rugarli, Elena I

2014-10-27

25

?2-adrenoceptor agonists in the regulation of mitochondrial biogenesis  

PubMed Central

The stimulation of mitochondrial biogenesis (MB) via cell surface G-protein coupled receptors is a promising strategy for cell repair and regeneration. Here we report the specificity and chemical rationale of a panel of ?2-adrenoceptor agonists with regards to MB. Using primary cultures of renal cells, a diverse panel of ?2-adrenoceptor agonists elicited three distinct phenotypes: full MB, partial MB, and non-MB. Full MB compounds had efficacy in the low nanomolar range and represent two chemical scaffolds containing three distinct chemical clusters. Interestingly, the MB phenotype did not correlate with reported receptor affinity or chemical similarity. Chemical clusters were then subjected to pharmacophore modeling creating two models with unique and distinct features, consisting of five conserved amongst full MB compounds were identified. The two discrete pharmacophore models were coalesced into a consensus pharmacophore with four unique features elucidating the spatial and chemical characteristics required to stimulate MB. PMID:23954364

Peterson, Yuri K.; Cameron, Robert B.; Wills, Lauren P.; Trager, Richard E.; Lindsey, Chris C.; Beeson, Craig C.; Schnellmann, Rick G.

2014-01-01

26

Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis.  

PubMed

Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor ? co-activator 1? (PGC-1?). PGC-1? regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1? has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1? remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1? content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group; ? = ?) were randomly assigned to sedentary (SED), forced-endurance (END) exercise (15 m/min for 90 min), or forced endurance +3 h of recovery (END+3h) group. The END group was sacrificed immediately after exercise, whereas the SED and END+3h groups were euthanized 3 h after acute exercise. Acute exercise coordinately increased the mRNA expression of nuclear and mitochondrial DNA-encoded mitochondrial transcripts. Nuclear and mitochondrial abundance of PGC-1? in END and END+3h groups was significantly higher versus SED mice. In mitochondria, PGC-1? is in a complex with mitochondrial transcription factor A at mtDNA D-loop, and this interaction was positively modulated by exercise, similar to the increased binding of PGC-1? at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1? re-localizes into nuclear and mitochondrial compartments where it functions as a transcriptional co-activator for both nuclear and mitochondrial DNA transcription factors. These results suggest that PGC-1? may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis. PMID:21245132

Safdar, Adeel; Little, Jonathan P; Stokl, Andrew J; Hettinga, Bart P; Akhtar, Mahmood; Tarnopolsky, Mark A

2011-03-25

27

Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy.  

PubMed

Damaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson's disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation. To constrain autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity and associates with both the mitochondria through binding Fis1 and the isolation membrane through the interactions with LC3/GABARAP family members. Another TBC family member TBC1D17, also participates in mitophagy and forms homodimers and heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. DOI: http://dx.doi.org/10.7554/eLife.01612.001. PMID:24569479

Yamano, Koji; Fogel, Adam I; Wang, Chunxin; van der Bliek, Alexander M; Youle, Richard J

2014-01-01

28

Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy  

PubMed Central

Damaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson’s disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation. To constrain autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity and associates with both the mitochondria through binding Fis1 and the isolation membrane through the interactions with LC3/GABARAP family members. Another TBC family member TBC1D17, also participates in mitophagy and forms homodimers and heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. DOI: http://dx.doi.org/10.7554/eLife.01612.001 PMID:24569479

Yamano, Koji; Fogel, Adam I; Wang, Chunxin; van der Bliek, Alexander M; Youle, Richard J

2014-01-01

29

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. PMID:20739683

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

2010-01-01

30

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

31

The effects of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function after glutamate excitotoxicity.  

PubMed

NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

Wang, Xiaowan; Li, Hailong; Ding, Shinghua

2014-01-01

32

Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK) cells?  

PubMed Central

Superoxide is widely regarded as the primary reactive oxygen species (ROS) which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK) cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1? expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ), a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS) inhibitor demonstrated that peroxynitrite (at low micromolar levels) induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation. PMID:24563852

Marine, Akira; Krager, Kimberly J.; Aykin-Burns, Nukhet; MacMillan-Crow, Lee Ann

2014-01-01

33

Peroxynitrite induced mitochondrial biogenesis following MnSOD knockdown in normal rat kidney (NRK) cells.  

PubMed

Superoxide is widely regarded as the primary reactive oxygen species (ROS) which initiates downstream oxidative stress. Increased oxidative stress contributes, in part, to many disease conditions such as cancer, atherosclerosis, ischemia/reperfusion, diabetes, aging, and neurodegeneration. Manganese superoxide dismutase (MnSOD) catalyzes the dismutation of superoxide into hydrogen peroxide which can then be further detoxified by other antioxidant enzymes. MnSOD is critical in maintaining the normal function of mitochondria, thus its inactivation is thought to lead to compromised mitochondria. Previously, our laboratory observed increased mitochondrial biogenesis in a novel kidney-specific MnSOD knockout mouse. The current study used transient siRNA mediated MnSOD knockdown of normal rat kidney (NRK) cells as the in vitro model, and confirmed functional mitochondrial biogenesis evidenced by increased PGC1? expression, mitochondrial DNA copy numbers and integrity, electron transport chain protein CORE II, mitochondrial mass, oxygen consumption rate, and overall ATP production. Further mechanistic studies using mitoquinone (MitoQ), a mitochondria-targeted antioxidant and L-NAME, a nitric oxide synthase (NOS) inhibitor demonstrated that peroxynitrite (at low micromolar levels) induced mitochondrial biogenesis. These findings provide the first evidence that low levels of peroxynitrite can initiate a protective signaling cascade involving mitochondrial biogenesis which may help to restore mitochondrial function following transient MnSOD inactivation. PMID:24563852

Marine, Akira; Krager, Kimberly J; Aykin-Burns, Nukhet; Macmillan-Crow, Lee Ann

2014-01-01

34

Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.  

PubMed

Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to maternal swimming. In conclusion, maternal swimming exercise induced neurometabolic programing in the offspring that could be of benefit to the rats against future cerebral insults. PMID:23639877

Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C

2013-08-29

35

Exercise-Mediated Wall Shear Stress Increases Mitochondrial Biogenesis in Vascular Endothelium  

PubMed Central

Objective Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs) using in vitro and in vivo complementary studies. Methods and Results Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2) for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (??m). Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds. Conclusion Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function. PMID:25375175

Kim, Boa; Lee, Hojun; Kawata, Keisuke; Park, Joon-Young

2014-01-01

36

Complementary RNA and Protein Profiling Identifies Iron as a Key Regulator of Mitochondrial Biogenesis  

PubMed Central

Summary Mitochondria are centers of metabolism and signaling whose content and function must adapt to changing cellular environments. The biological signals that initiate mitochondrial restructuring and the cellular processes that drive this adaptive response are largely obscure. To better define these systems, we performed matched quantitative genomic and proteomic analyses of mouse muscle cells as they performed mitochondrial biogenesis. We find that proteins involved in cellular iron homeostasis are highly coordinated with this process and that depletion of cellular iron results in a rapid, dose-dependent decrease of select mitochondrial protein levels and oxidative capacity. We further show that this process is universal across a broad range of cell types and fully reversed when iron is reintroduced. Collectively, our work reveals that cellular iron is a key regulator of mitochondrial biogenesis, and provides quantitative data sets that can be leveraged to explore posttranscriptional and posttranslational processes that are essential for mitochondrial adaptation. PMID:23318259

Rensvold, Jarred W.; Ong, Shao-En; Jeevananthan, Athavi; Carr, Steven A.; Mootha, Vamsi K.; Pagliarini, David J.

2013-01-01

37

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

SciTech Connect

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{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} 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{sub 2} 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{sub 2} 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. -- Highlights: ? We supplemented rats with CoCl{sub 2} for 15 days along with training. ? CoCl{sub 2} supplementation augmented endurance performance and aerobic respiration. ? It increased glucose uptake and metabolism in muscle. ? It enhanced mitochondrial biogenesis in red gastrocnemius muscle.

Saxena, Saurabh [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)] [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India); Shukla, Dhananjay [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India)] [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India); Bansal, Anju, E-mail: anjubansaldipas@gmail.com [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)] [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)

2012-11-01

38

Mitochondrial biogenesis restores oxidative metabolism during Staphylococcus aureus sepsis  

Microsoft Academic Search

Rationale: The extent, timing, and significance of mitochondrial injury and recovery in bacterial sepsis are poorly characterized, although oxidative and nitrosative mitochondrial damage have been implicated in the development of organ failure. Objectives: To define the relationships between mitochondrial bio- genesis, oxidative metabolism, and recovery from Staphylococcus aureus sepsis. Methods: We developed a murine model of fibrin clot peritonitis, using

Douglas W. Haden; Hagir B. Suliman; Martha Sue Carraway; Karen E. Welty-Wolf; Abdelwahid S. Ali; Hiroshi Shitara; Hiromichi Yonekawa; Claude A. Piantadosi

2007-01-01

39

Turn up the power - pharmacological activation of mitochondrial biogenesis in mouse models.  

PubMed

The oxidative phosphorylation (OXPHOS) system in mitochondria is responsible for the generation of the majority of cellular energy in the form of ATP. Patients with genetic OXPHOS disorders form the largest group of inborn errors of metabolism. Unfortunately, there is still a lack of efficient therapies for these disorders other than management of symptoms. Developing therapies has been complicated because, although the total group of OXPHOS patients is relatively large, there is enormous clinical and genetic heterogeneity within this patient population. Thus there has been a lot of interest in generating relevant mouse models for the different kinds of OXPHOS disorders. The most common treatment strategies tested in these mouse models have aimed to up-regulate mitochondrial biogenesis, in order to increase the residual OXPHOS activity present in affected animals and thereby to ameliorate the energy deficiency. Drugs such as bezafibrate, resveratrol and AICAR target the master regulator of mitochondrial biogenesis PGC-1? either directly or indirectly to manipulate mitochondrial metabolism. This review will summarize the outcome of preclinical treatment trials with these drugs in mouse models of OXPHOS disorders and discuss similar treatments in a number of mouse models of common diseases in which pathology is closely linked to mitochondrial dysfunction. In the majority of these studies the pharmacological activation of the PGC-1? axis shows true potential as therapy; however, other effects besides mitochondrial biogenesis may be contributing to this as well. PMID:24102298

Komen, J C; Thorburn, D R

2014-04-01

40

Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes  

PubMed Central

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, ?-hydroxy-?-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5?mM), alanine (0.5?mM), valine (0.5?mM), EX527 (SIRT1 inhibitor, 25??M), and Compound C (AMPK inhibitor, 25??M) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD+, SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event.

Liang, Chunzi; Curry, Benjamin J.; Brown, Patricia L.; Zemel, Michael B.

2014-01-01

41

Mild mitochondrial uncoupling does not affect mitochondrial biogenesis but downregulates pyruvate carboxylase in adipocytes: role for triglyceride content reduction.  

PubMed

In adipocytes, mitochondrial uncoupling is known to trigger a triglyceride loss comparable with the one induced by TNF?, a proinflammatory cytokine. However, the impact of a mitochondrial uncoupling on the abundance/composition of mitochondria and its connection with triglyceride content in adipocytes is largely unknown. In this work, the effects of a mild mitochondrial uncoupling triggered by FCCP were investigated on the mitochondrial population of 3T3-L1 adipocytes by both quantitative and qualitative approaches. We found that mild mitochondrial uncoupling does not stimulate mitochondrial biogenesis in adipocytes but induces an adaptive cell response characterized by quantitative modifications of mitochondrial protein content. Superoxide anion radical level was increased in mitochondria of both TNF?- and FCCP-treated adipocytes, whereas mitochondrial DNA copy number was significantly higher only in TNF?-treated cells. Subproteomic analysis revealed that the abundance of pyruvate carboxylase was reduced significantly in mitochondria of TNF?- and FCCP-treated adipocytes. Functional study showed that overexpression of this major enzyme of lipid metabolism is able to prevent the triglyceride content reduction in adipocytes exposed to mitochondrial uncoupling or TNF?. These results suggest a new mechanism by which the effects of mitochondrial uncoupling might limit triglyceride accumulation in adipocytes. PMID:22354779

De Pauw, Aurélia; Demine, Stéphane; Tejerina, Silvia; Dieu, Marc; Delaive, Edouard; Kel, Alexander; Renard, Patricia; Raes, Martine; Arnould, Thierry

2012-05-15

42

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

PubMed Central

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 skeletal muscle, in part due to an increase in mitochondrial biogenesis. Furthermore, we observe that the prevention of mitochondrial dysfunction by BBR, the increase in mitochondrial biogenesis, as well as BBR-induced AMPK activation, are blocked in cells in which SIRT1 has been knocked-down. Taken together, these data reveal an important role for SIRT1 and mitochondrial biogenesis in the preventive effects of BBR on diet-induced insulin resistance. PMID:22027215

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

2012-01-01

43

Short Term Exercise Induces PGC-1?, Ameliorates Inflammation and Increases Mitochondrial Membrane Proteins but Fails to Increase Respiratory Enzymes in Aging Diabetic Hearts  

PubMed Central

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

2013-01-01

44

Defects in Mitochondrial Fatty Acid Synthesis Result in Failure of Multiple Aspects of Mitochondrial Biogenesis in Saccharomyces cerevisiae  

PubMed Central

Summary Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle as a common substrate and is required for the production of octanoic acid (C8) precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway essential for respiration. In a genetic screen in Saccharomyces cerevisiae designed to further elucidate the physiological role of mtFAS, we isolated mutants with defects in mitochondrial post-translational gene expression processes, indicating a novel link to mitochondrial gene expression and respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but not lipoylation per se, is required for respiratory competence. We demonstrate that mtFAS is required for mRNA splicing, mitochondrial translation and respiratory complex assembly, and provide evidence that not LA per se, but fatty acids longer than C8 play a role in these processes. We also show that mtFAS- and LA-deficient strains suffer from a mild heme deficiency that may contribute to the respiratory complex assembly defect. Based on our data and previously published information, we propose a model implicating mtFAS as a sensor for mitochondrial acetyl-CoA availability and a coordinator of nuclear and mitochondrial gene expression by adapting the mitochondrial compartment to changes in the metabolic status of the cell. PMID:24102902

Kursu, V. A. Samuli; Pietikainen, Laura P.; Fontanesi, Flavia; Aaltonen, Mari J.; Suomi, Fumi; Nair, Remya Raghavan; Schonauer, Melissa S.; Dieckmann, Carol L.; Barrientos, Antoni; Hiltunen, J. Kalervo; Kastaniotis, Alexander J.

2014-01-01

45

Defects in mitochondrial fatty acid synthesis result in failure of multiple aspects of mitochondrial biogenesis in Saccharomyces cerevisiae.  

PubMed

Mitochondrial fatty acid synthesis (mtFAS) shares acetyl-CoA with the Krebs cycle as a common substrate and is required for the production of octanoic acid (C8) precursors of lipoic acid (LA) in mitochondria. MtFAS is a conserved pathway essential for respiration. In a genetic screen in Saccharomyces cerevisiae designed to further elucidate the physiological role of mtFAS, we isolated mutants with defects in mitochondrial post-translational gene expression processes, indicating a novel link to mitochondrial gene expression and respiratory chain biogenesis. In our ensuing analysis, we show that mtFAS, but not lipoylation per se, is required for respiratory competence. We demonstrate that mtFAS is required for mRNA splicing, mitochondrial translation and respiratory complex assembly, and provide evidence that not LA?per se, but fatty acids longer than C8 play a role in these processes. We also show that mtFAS- and LA-deficient strains suffer from a mild haem deficiency that may contribute to the respiratory complex assembly defect. Based on our data and previously published information, we propose a model implicating mtFAS as a sensor for mitochondrial acetyl-CoA availability and a co-ordinator of nuclear and mitochondrial gene expression by adapting the mitochondrial compartment to changes in the metabolic status of the cell. PMID:24102902

Kursu, V A Samuli; Pietikäinen, Laura P; Fontanesi, Flavia; Aaltonen, Mari J; Suomi, Fumi; Raghavan Nair, Remya; Schonauer, Melissa S; Dieckmann, Carol L; Barrientos, Antoni; Hiltunen, J Kalervo; Kastaniotis, Alexander J

2013-11-01

46

Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes  

PubMed Central

Using an siRNA-based screen, we identified the transcriptional corepressor RIP140 as a negative regulator of insulin-responsive hexose uptake and oxidative metabolism in 3T3-L1 adipocytes. Affymetrix GeneChip profiling revealed that RIP140 depletion upregulates the expression of clusters of genes in the pathways of glucose uptake, glycolysis, TCA cycle, fatty acid oxidation, mitochondrial biogenesis, and oxidative phosphorylation in these cells. Conversely, we show that reexpression of RIP140 in mouse embryonic fibroblasts derived from RIP140-null mice downregulates expression of many of these same genes. Consistent with these microarray data, RIP140 gene silencing in cultured adipocytes increased both conversion of [14C]glucose to CO2 and mitochondrial oxygen consumption. RIP140-null mice, previously reported to resist weight gain on a high-fat diet, are shown here to display enhanced glucose tolerance and enhanced responsiveness to insulin compared with matched wild-type mice upon high-fat feeding. Mechanistically, RIP140 was found to require the nuclear receptor ERR? to regulate hexose uptake and mitochondrial proteins SDHB and CoxVb, although it likely acts through other nuclear receptors as well. We conclude that RIP140 is a major suppressor of adipocyte oxidative metabolism and mitochondrial biogenesis, as well as a negative regulator of whole-body glucose tolerance and energy expenditure in mice. PMID:16374519

Powelka, Aimee M.; Seth, Asha; Virbasius, Joseph V.; Kiskinis, Evangelos; Nicoloro, Sarah M.; Guilherme, Adilson; Tang, Xiaoqing; Straubhaar, Juerg; Cherniack, Andrew D.; Parker, Malcolm G.; Czech, Michael P.

2005-01-01

47

Perfluorooctanoate, perflourooctanesulfonate, and N-ethyl perfluorooctanesulfonamido ethanol; peroxisome proliferation and mitochondrial biogenesis.  

PubMed

Compounds that cause peroxisome proliferation in rats and mice have been reported to interfere with mitochondrial (mt) bioenergetics and possibly biogenesis. The purpose of this investigation was to establish whether proliferation of peroxisomes and mitochondria are necessarily related. Perfluorooctanesulfonate (PFOS) and N-ethyl perfluorooctanesulfonamido ethanol (N-EtFOSE) were investigated as peroxisome proliferators in comparison to perfluorooctanoic acid (PFOA). Three parameters were chosen to assess peroxisome proliferation, stimulation of lauroyl CoA oxidase activity, reduction of serum cholesterol concentration, and hepatomegaly. mt Biogenesis was assessed through cytochrome oxidase activity, cytochrome content and mitochondrial DNA (mtDNA) copy number. PFOA, PFOS, or N-EtFOSE was administered via a single i.p. injection at 100 mg/kg in male rats, and measurements were made 3 days later. In this model, PFOS and PFOA share similar potencies as peroxisome proliferators, whereas N-EtFOSE showed no activity. mt Endpoints were altered only in the PFOA treatment group, which consisted of a decrease cytochrome oxidase activity in liver tissue and an increase in the mtDNA copy number. None of the perfluorooctanoates significantly altered mt cytochrome content following acute in vivo treatment. These data demonstrate that acute administration of PFOS or PFOA causes hepatic peroxisome proliferation in rats. However, stimulation of mt biogenesis is not a characteristic response of all peroxisome proliferators. PMID:11879971

Berthiaume, Jessica; Wallace, Kendall B

2002-03-24

48

Silybin exerts antioxidant effects and induces mitochondrial biogenesis in liver of rat with secondary biliary cirrhosis.  

PubMed

The accumulation of toxic hydrophobic bile acids in hepatocytes, observed during chronic cholestasis, induces substantial modification in the redox state and in mitochondrial functions. Recent reports have suggested a significant role of impaired lipid metabolism in the progression of chronic cholestasis. In this work we report that changes observed in the expression of the lipogenic enzymes acetyl-CoA carboxylase and fatty acid synthase were associated with a decrease in the activity of citrate carrier (CIC), a protein of the inner mitochondrial membrane closely related to hepatic lipogenesis. We also verified that the impairment of citrate transport was dependent on modification of the phospholipid composition of the mitochondrial membrane and on cardiolipin oxidation. Silybin, an extract of silymarin with antioxidant and anti-inflammatory properties, prevented mitochondrial reactive oxygen species (ROS) production, cardiolipin oxidation, and CIC failure in cirrhotic livers but did not affect the expression of lipogenic enzymes. Moreover, supplementation of silybin was also associated with mitochondrial biogenesis. In conclusion, we demonstrate that chronic cholestasis induces cardiolipin oxidation that in turn impairs mitochondrial function and further promotes ROS production. The capacity of silybin to limit mitochondrial failure is part of its hepatoprotective property. PMID:24819445

Serviddio, Gaetano; Bellanti, Francesco; Stanca, Eleonora; Lunetti, Paola; Blonda, Maria; Tamborra, Rosanna; Siculella, Luisa; Vendemiale, Gianluigi; Capobianco, Loredana; Giudetti, Anna Maria

2014-08-01

49

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1? expression.  

PubMed

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1? (PGC-1?) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits-NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1? was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1? in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1? seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. PMID:24084166

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J L; Bal, Amanjit; Gill, Kiran Dip

2013-12-01

50

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

PubMed Central

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 energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK. PMID:22808092

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

2012-01-01

51

A Combination of Nutriments Improves Mitochondrial Biogenesis and Function in Skeletal Muscle of Type 2 Diabetic Goto-Kakizaki Rats  

Microsoft Academic Search

BackgroundRecent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis\\/function in skeletal muscle of type 2 diabetic Goto–Kakizaki

Weili Shen; Jiejie Hao; Chuan Tian; Jinmin Ren; Lu Yang; Xuesen Li; Cheng Luo; Carl W. Cotma; Jiankang Liu; Don Husereau

2008-01-01

52

R -?-Lipoic acid and acetyl- l -carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes  

Microsoft Academic Search

Aims\\/hypothesis  The aim of the study was to address the importance of mitochondrial function in insulin resistance and type 2 diabetes, and\\u000a also to identify effective agents for ameliorating insulin resistance in type 2 diabetes. We examined the effect of two mitochondrial\\u000a nutrients, R-?-lipoic acid (LA) and acetyl-l-carnitine (ALC), as well as their combined effect, on mitochondrial biogenesis in 3T3-L1 adipocytes.

W. Shen; K. Liu; C. Tian; L. Yang; X. Li; J. Ren; L. Packer; C. W. Cotman; J. Liu

2008-01-01

53

PGC-1? mediates mitochondrial biogenesis and oxidative phosphorylation in cancer cells to promote metastasis.  

PubMed

Cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate the cellular building blocks required for tumour growth. However, the specific bioenergetic profile of invasive and metastatic cancer cells is unknown. Here we report that migratory/invasive cancer cells specifically favour mitochondrial respiration and increased ATP production. Invasive cancer cells use the transcription coactivator peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PPARGC1A, also known as PGC-1?) to enhance oxidative phosphorylation, mitochondrial biogenesis and the oxygen consumption rate. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1? expression in invasive cancer cells and the formation of distant metastases. Silencing of PGC-1? in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumour growth or the epithelial-to-mesenchymal program. Inherent genetics of cancer cells can determine the transcriptome framework associated with invasion and metastasis, and mitochondrial biogenesis and respiration induced by PGC-1? are also essential for functional motility of cancer cells and metastasis. PMID:25241037

LeBleu, Valerie S; O'Connell, Joyce T; Gonzalez Herrera, Karina N; Wikman, Harriet; Pantel, Klaus; Haigis, Marcia C; de Carvalho, Fernanda Machado; Damascena, Aline; Domingos Chinen, Ludmilla Thome; Rocha, Rafael M; Asara, John M; Kalluri, Raghu

2014-10-01

54

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. PMID:23242154

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

2012-01-01

55

Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle  

PubMed Central

Background Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. Methods C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Results Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid ?-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1? expression in the skeletal muscle. Conclusions Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders. PMID:25114710

2014-01-01

56

Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice.  

PubMed

Androgen reduces fat mass, although the underlying mechanisms are unknown. Here, we examined the effect of testosterone on heat production and mitochondrial biogenesis. Testosterone-treated mice exhibited elevated heat production. Treatment with testosterone increased the expression level of peroxisome proliferator-activated receptor-? coactivator-1? (PGC1?), ATP5B and Cox4 in skeletal muscle, but not that in brown adipose tissue and liver. mRNA levels of genes involved in mitochondrial biogenesis were elevated in skeletal muscle isolated from testosterone-treated male mice, but were down-regulated in androgen receptor deficient mice. These results demonstrated that the testosterone-induced increase in energy expenditure is derived from elevated mitochondrial biogenesis in skeletal muscle. PMID:24726723

Usui, Taro; Kajita, Kazuo; Kajita, Toshiko; Mori, Ichiro; Hanamoto, Takayuki; Ikeda, Takahide; Okada, Hideyuki; Taguchi, Koichiro; Kitada, Yoshihiko; Morita, Hiroyuki; Sasaki, Tsutomu; Kitamura, Tadahiro; Sato, Takashi; Kojima, Itaru; Ishizuka, Tatsuo

2014-05-21

57

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

2013-02-01

58

Oxaloacetate activates brain mitochondrial biogenesis, enhances the insulin pathway, reduces inflammation and stimulates neurogenesis.  

PubMed

Brain bioenergetic function declines in some neurodegenerative diseases, this may influence other pathologies and administering bioenergetic intermediates could have therapeutic value. To test how one intermediate, oxaloacetate (OAA) affects brain bioenergetics, insulin signaling, inflammation and neurogenesis, we administered intraperitoneal OAA, 1-2 g/kg once per day for 1-2 weeks, to C57Bl/6 mice. OAA altered levels, distributions or post-translational modifications of mRNA and proteins (proliferator-activated receptor-gamma coactivator 1?, PGC1 related co-activator, nuclear respiratory factor 1, transcription factor A of the mitochondria, cytochrome oxidase subunit 4 isoform 1, cAMP-response element binding, p38 MAPK and adenosine monophosphate-activated protein kinase) in ways that should promote mitochondrial biogenesis. OAA increased Akt, mammalian target of rapamycin and P70S6K phosphorylation. OAA lowered nuclear factor ?B nucleus-to-cytoplasm ratios and CCL11 mRNA. Hippocampal vascular endothelial growth factor mRNA, doublecortin mRNA, doublecortin protein, doublecortin-positive neuron counts and neurite length increased in OAA-treated mice. (1)H-MRS showed OAA increased brain lactate, GABA and glutathione thereby demonstrating metabolic changes are detectable in vivo. In mice, OAA promotes brain mitochondrial biogenesis, activates the insulin signaling pathway, reduces neuroinflammation and activates hippocampal neurogenesis. PMID:25027327

Wilkins, Heather M; Harris, Janna L; Carl, Steven M; E, Lezi; Lu, Jianghua; Eva Selfridge, J; Roy, Nairita; Hutfles, Lewis; Koppel, Scott; Morris, Jill; Burns, Jeffrey M; Michaelis, Mary L; Michaelis, Elias K; Brooks, William M; Swerdlow, Russell H

2014-12-15

59

Suppressed mitochondrial biogenesis in folic acid-induced acute kidney injury and early fibrosis.  

PubMed

Acute kidney injury (AKI) is a disease with mitochondrial dysfunction and a newly established risk factor for the development of chronic kidney disease (CKD) and fibrosis. We examined mitochondrial homeostasis in the folic acid (FA)-induced AKI model that develops early fibrosis over a rapid time course. Mice given a single dose of FA had elevated serum creatinine (3-fold) and urine glucose (2.2-fold) 1 and 2 d after injection that resolved by 4d. In contrast, peroxisome proliferator gamma coactivator 1? (PGC-1?) and mitochondrial transcription factor A (TFAM), critical transcriptional regulators of mitochondrial biogenesis (MB), were down-regulated ?80% 1d after FA injection and remained depressed through 14 d. Multiple electron transport chain and ATP synthesis genes were also down-regulated from 1 to 14 d after FA, including NADH dehydrogenase (ubiquinone) 1 beta subcomplex 8 (NDUF?8), ATP synthase subunit ? (ATPS-?), and cytochrome C oxidase subunit I (COXI). Mitochondrial DNA copy number was reduced ?50% from 2 to 14 d after FA injection. Protein levels of early fibrosis markers ?-smooth muscle actin and transforming growth factor ?1 were elevated at 6 and 14 d after FA. Picrosirius red staining and collagen 1A2 (COL1A2) IHC revealed staining for mature collagen deposition at 14 d. We propose that mitochondrial dysfunction induced by AKI is a persistent cellular injury that promotes progression to fibrosis and CKD, and that this model can be used to test mitochondrial therapeutics that limit progression to fibrosis and CKD. PMID:24275386

Stallons, L Jay; Whitaker, Ryan M; Schnellmann, Rick G

2014-01-30

60

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. PMID:21942988

2011-01-01

61

Transient hypoxia stimulates mitochondrial biogenesis in brain subcortex by a neuronal nitric oxide synthase-dependent mechanism.  

PubMed

The adaptive mechanisms that protect brain metabolism during and after hypoxia, for instance, during hypoxic preconditioning, are coordinated in part by nitric oxide (NO). We tested the hypothesis that acute transient hypoxia stimulates NO synthase (NOS)-activated mechanisms of mitochondrial biogenesis in the hypoxia-sensitive subcortex of wild-type (Wt) and neuronal NOS (nNOS) and endothelial NOS (eNOS)-deficient mice. Mice were exposed to hypobaric hypoxia for 6 h, and changes in immediate hypoxic transcriptional regulation of mitochondrial biogenesis was assessed in relation to mitochondrial DNA (mtDNA) content and mitochondrial density. There were no differences in cerebral blood flow or hippocampal PO2 responses to acute hypoxia among these strains of mice. In Wt mice, hypoxia increased mRNA levels for peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1 alpha), nuclear respiratory factor-1, and mitochondrial transcription factor A. After 24 h, new mitochondria, localized in reporter mice expressing mitochondrial green fluorescence protein, were seen primarily in hippocampal neurons. eNOS-/- mice displayed lower basal levels but maintained hypoxic induction of these transcripts. In contrast, nuclear transcriptional regulation of mitochondrial biogenesis in nNOS-/- mice was normal at baseline but did not respond to hypoxia. After hypoxia, subcortical mtDNA content increased in Wt and eNOS-/- mice but not in nNOS-/- mice. Hypoxia stimulated PGC-1alpha protein expression and phosphorylation of protein kinase A and cAMP response element binding (CREB) protein in Wt mice, but CREB only was activated in eNOS-/- mice and not in nNOS-/- mice. These findings demonstrate that hypoxic preconditioning elicits subcortical mitochondrial biogenesis by a novel mechanism that requires nNOS regulation of PGC-1alpha and CREB. PMID:18305236

Gutsaeva, Diana R; Carraway, Martha Sue; Suliman, Hagir B; Demchenko, Ivan T; Shitara, Hiroshi; Yonekawa, Hiromichi; Piantadosi, Claude A

2008-02-27

62

TSC-mTOR maintains quiescence and function of hematopoietic stem cells by repressing mitochondrial biogenesis and reactive oxygen species  

Microsoft Academic Search

The tuberous sclerosis complex (TSC) - mammalian target of rapamycin (mTOR) pathway is a key regulator of cellular metabolism. We used conditional deletion of Tsc1 to address how quiescence is associated with the function of hematopoietic stem cells (HSCs). We demonstrate that Tsc1 deletion in the HSCs drives them from quiescence into rapid cy- cling, with increased mitochondrial biogenesis and

Chong Chen; Yu Liu; Runhua Liu; Tsuneo Ikenoue; Kun-Liang Guan; Yang Liu; Pan Zheng

2008-01-01

63

Gamma rays induce a p53-independent mitochondrial biogenesis that is counter-regulated by HIF1?  

PubMed Central

Mitochondrial biogenesis is an orchestrated process that presides to the regulation of the organelles homeostasis within a cell. We show that ?-rays, at doses commonly used in the radiation therapy for cancer treatment, induce an increase in mitochondrial mass and function, in response to a genotoxic stress that pushes cells into senescence, in the presence of a functional p53. Although the main effector of the response to ?-rays is the p53-p21 axis, we demonstrated that mitochondrial biogenesis is only indirectly regulated by p53, whose activation triggers a murine double minute 2 (MDM2)-mediated hypoxia-inducible factor 1? (HIF1?) degradation, leading to the release of peroxisome-proliferator activated receptor gamma co-activator 1? inhibition by HIF1?, thus promoting mitochondrial biogenesis. Mimicking hypoxia by HIF1? stabilization, in fact, blunts the mitochondrial response to ?-rays as well as the induction of p21-mediated cell senescence, indicating prevalence of the hypoxic over the genotoxic response. Finally, we also show in vivo that post-radiotherapy mitochondrial DNA copy number increase well correlates with lack of HIF1? increase in the tissue, concluding this may be a useful molecular tool to infer the trigger of a hypoxic response during radiotherapy, which may lead to failure of activation of cell senescence. PMID:23764844

Bartoletti-Stella, A; Mariani, E; Kurelac, I; Maresca, A; Caratozzolo, M F; Iommarini, L; Carelli, V; Eusebi, L H; Guido, A; Cenacchi, G; Fuccio, L; Rugolo, M; Tullo, A; Porcelli, A M; Gasparre, G

2013-01-01

64

Induction of mitochondrial biogenesis protects against caspase-dependent and caspase-independent apoptosis in L6 myoblasts.  

PubMed

Apoptotic signaling plays an important role in skeletal muscle degradation, atrophy, and dysfunction. Mitochondria are central executers of apoptosis by directly participating in caspase-dependent and caspase-independent cell death signaling. Given the important apoptotic role of mitochondria, altering mitochondrial content could influence apoptosis. Therefore, we examined the direct effect of modest, but physiological increases in mitochondrial biogenesis and content on skeletal muscle apoptosis using a cell culture approach. Treatment of L6 myoblasts with SNAP or AICAR (5h/day for 5days) significantly increased PGC-1, AIF, cytochrome c, and MnSOD protein content as well as MitoTracker staining. Following induction of mitochondrial biogenesis, L6 myoblasts displayed decreased sensitivity to apoptotic cell death as well as reduced caspase-3 and caspase-9 activation following exposure to staurosporine (STS) and C2-ceramide. L6 myoblasts with higher mitochondrial content also exhibited reduced apoptosis and AIF release following exposure to hydrogen peroxide (H2O2). Analysis of several key apoptosis regulatory proteins (ARC, Bax, Bcl-2, XIAP), antioxidant proteins (catalase, MnSOD, CuZnSOD), and reactive oxygen species (ROS) measures (DCF and MitoSOX fluorescence) revealed that these mechanisms were not responsible for the observed cellular protection. However, myoblasts with higher mitochondrial content were less sensitive to Ca(2+)-induced mitochondrial permeability transition pore formation (mPTP) and mitochondrial membrane depolarization. Collectively, these data demonstrate that increased mitochondrial content at physiological levels provides protection against apoptotic cell death by decreasing caspase-dependent and caspase-independent signaling through influencing mitochondrial Ca(2+)-mediated apoptotic events. Therefore, increasing mitochondrial biogenesis/content may represent a potential therapeutic approach in skeletal muscle disorders displaying increased apoptosis. PMID:23643731

Dam, Aaron D; Mitchell, Andrew S; Quadrilatero, Joe

2013-12-01

65

Rosiglitazone-Induced Mitochondrial Biogenesis in White Adipose Tissue Is Independent of Peroxisome Proliferator-Activated Receptor ? Coactivator-1?  

PubMed Central

Background Thiazolidinediones, a family of insulin-sensitizing drugs commonly used to treat type 2 diabetes, are thought to exert their effects in part by promoting mitochondrial biogenesis in white adipose tissue through the transcriptional coactivator PGC-1? (Peroxisome Proliferator-Activated Receptor ? Coactivator-1?). Methodology/Principal Findings To assess the role of PGC-1? in the control of rosiglitazone-induced mitochondrial biogenesis, we have generated a mouse model that lacks expression of PGC-1? specifically in adipose tissues (PGC-1?-FAT-KO mice). We found that expression of genes encoding for mitochondrial proteins involved in oxidative phosphorylation, tricarboxylic acid cycle or fatty acid oxidation, was similar in white adipose tissue of wild type and PGC-1?-FAT-KO mice. Furthermore, the absence of PGC-1? did not prevent the positive effect of rosiglitazone on mitochondrial gene expression or biogenesis, but it precluded the induction by rosiglitazone of UCP1 and other brown fat-specific genes in white adipose tissue. Consistent with the in vivo findings, basal and rosiglitazone-induced mitochondrial gene expression in 3T3-L1 adipocytes was unaffected by the knockdown of PGC-1? but it was impaired when PGC-1? expression was knockdown by the use of specific siRNA. Conclusions/Significance These results indicate that in white adipose tissue PGC-1? is dispensable for basal and rosiglitazone-induced mitochondrial biogenesis but required for the rosiglitazone-induced expression of UCP1 and other brown adipocyte-specific markers. Our study suggests that PGC-1? is important for the appearance of brown adipocytes in white adipose tissue. Our findings also provide evidence that PGC-1? and not PGC-1? regulates basal and rosiglitazone-induced mitochondrial gene expression in white adipocytes. PMID:22087241

Pardo, Rosario; Enguix, Natàlia; Lasheras, Jaime; Feliu, Juan E.; Kralli, Anastasia; Villena, Josep A.

2011-01-01

66

Promoting PGC-1?-driven mitochondrial biogenesis is detrimental in pressure-overloaded mouse hearts.  

PubMed

Mitochondrial dysfunction in animal models of heart failure is associated with downregulation of the peroxisome proliferator-activated receptor-? coactivator (PGC)-1? pathway. To test whether PGC-1? is an appropriate therapeutic target for increasing mitochondrial biogenesis and improving function in heart failure, we used a transgenic (TG) mouse model of moderate overexpression of PGC-1? (?3-fold) in the heart. TG mice had small increases in citrate synthase activity and mitochondria size in the heart without alterations in myocardial energetics or cardiac function at baseline. In vivo dobutamine stress increased fractional shortening in wild-type mice, but this increase was attenuated in TG mice, whereas ex vivo isolated perfused TG hearts demonstrated normal functional and energetic response to high workload challenge. When subjected to pressure overload by transverse aortic constriction (TAC), TG mice displayed a significantly greater acute mortality for both male and female mice; however, long-term survival up to 8 wk was similar between the two groups. TG mice also showed a greater decrease in fractional shortening and a greater increase in left ventricular chamber dimension in response to TAC. Mitochondrial gene expression and citrate synthase activity were mildly increased in TG mice compared with wild-type mice, and this difference was also maintained after TAC. Our data suggest that a moderate level of PGC-1? overexpression in the heart compromises acute survival and does not improve cardiac function during chronic pressure overload in mice. PMID:25172896

Karamanlidis, Georgios; Garcia-Menendez, Lorena; Kolwicz, Stephen C; Lee, Chi Fung; Tian, Rong

2014-11-01

67

Epigallocatechin-3-gallate prevents oxidative phosphorylation deficit and promotes mitochondrial biogenesis in human cells from subjects with Down's syndrome.  

PubMed

A critical role for mitochondrial dysfunction has been proposed in the pathogenesis of Down's syndrome (DS), a human multifactorial disorder caused by trisomy of chromosome 21, associated with mental retardation and early neurodegeneration. Previous studies from our group demonstrated in DS cells a decreased capacity of the mitochondrial ATP production system and overproduction of reactive oxygen species (ROS) in mitochondria. In this study we have tested the potential of epigallocatechin-3-gallate (EGCG) - a natural polyphenol component of green tea - to counteract the mitochondrial energy deficit found in DS cells. We found that EGCG, incubated with cultured lymphoblasts and fibroblasts from DS subjects, rescued mitochondrial complex I and ATP synthase catalytic activities, restored oxidative phosphorylation efficiency and counteracted oxidative stress. These effects were associated with EGCG-induced promotion of PKA activity, related to increased cellular levels of cAMP and PKA-dependent phosphorylation of the NDUFS4 subunit of complex I. In addition, EGCG strongly promoted mitochondrial biogenesis in DS cells, as associated with increase in Sirt1-dependent PGC-1? deacetylation, NRF-1 and T-FAM protein levels and mitochondrial DNA content. In conclusion, this study shows that EGCG is a promoting effector of oxidative phosphorylation and mitochondrial biogenesis in DS cells, acting through modulation of the cAMP/PKA- and sirtuin-dependent pathways. EGCG treatment promises thus to be a therapeutic approach to counteract mitochondrial energy deficit and oxidative stress in DS. PMID:23291000

Valenti, Daniela; De Rasmo, Domenico; Signorile, Anna; Rossi, Leonardo; de Bari, Lidia; Scala, Iris; Granese, Barbara; Papa, Sergio; Vacca, Rosa Anna

2013-04-01

68

Lysocardiolipin acyltransferase 1 (ALCAT1) controls mitochondrial DNA fidelity and biogenesis through modulation of MFN2 expression  

PubMed Central

Oxidative stress causes mitochondrial fragmentation and dysfunction in age-related diseases through unknown mechanisms. Cardiolipin (CL) is a phospholipid required for mitochondrial oxidative phosphorylation. The function of CL is determined by its acyl composition, which is significantly altered by the onset of age-related diseases. Here, we examine a role of acyl-CoA:lysocardiolipin acyltransferase lysocardiolipin acyltransferase 1 (ALCAT1), a lysocardiolipin acyltransferase that catalyzes pathological CL remodeling, in mitochondrial biogenesis. We show that overexpression of ALCAT1 causes mitochondrial fragmentation through oxidative stress and depletion of mitofusin mitofusin 2 (MFN2) expression. Strikingly, ALCAT1 overexpression also leads to mtDNA instability and depletion that are reminiscent of MFN2 deficiency. Accordingly, expression of MFN2 completely rescues mitochondrial fusion defect and respiratory dysfunction. Furthermore, ablation of ALCAT1 prevents mitochondrial fragmentation from oxidative stress by up-regulating MFN2 expression, mtDNA copy number, and mtDNA fidelity. Together, these findings reveal an unexpected role of CL remodeling in mitochondrial biogenesis, linking oxidative stress by ALCAT1 to mitochondrial fusion defect. PMID:22509026

Li, Jia; Liu, Xiaolei; Wang, Huayan; Zhang, Weiping; Chan, David C.; Shi, Yuguang

2012-01-01

69

Exercise training induces mitochondrial biogenesis and glucose uptake in subcutaneous adipose tissue through eNOS-dependent mechanisms.  

PubMed

Insulin resistance and obesity are associated with a reduction of mitochondrial content in various tissues of mammals. Moreover, a reduced nitric oxide (NO) bioavailability impairs several cellular functions, including mitochondrial biogenesis and insulin-stimulated glucose uptake, two important mechanisms of body adaptation in response to physical exercise. Although these mechanisms have been thoroughly investigated in skeletal muscle and heart, few studies have focused on the effects of exercise on mitochondria and glucose metabolism in adipose tissue. In this study, we compared the in vivo effects of chronic exercise in subcutaneous adipose tissue of wild-type (WT) and endothelial NO synthase (eNOS) knockout (eNOS(-/-)) mice after a swim training period. We then investigated the in vitro effects of NO on mouse 3T3-L1 and human subcutaneous adipose tissue-derived adipocytes after a chronic treatment with an NO donor: diethylenetriamine-NO (DETA-NO). We observed that swim training increases mitochondrial biogenesis, mitochondrial DNA content, and glucose uptake in subcutaneous adipose tissue of WT but not eNOS(-/-) mice. Furthermore, we observed that DETA-NO promotes mitochondrial biogenesis and elongation, glucose uptake, and GLUT4 translocation in cultured murine and human adipocytes. These results point to the crucial role of the eNOS-derived NO in the metabolic adaptation of subcutaneous adipose tissue to exercise training. PMID:24622799

Trevellin, Elisabetta; Scorzeto, Michele; Olivieri, Massimiliano; Granzotto, Marnie; Valerio, Alessandra; Tedesco, Laura; Fabris, Roberto; Serra, Roberto; Quarta, Marco; Reggiani, Carlo; Nisoli, Enzo; Vettor, Roberto

2014-08-01

70

AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1.  

PubMed

Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor ? coactivator-1 (PGC-1?), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1? and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1? nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1? target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (~5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ~1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export. PMID:24081905

Corum, Daniel G; Tsichlis, Philip N; Muise-Helmericks, Robin C

2014-01-01

71

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. PMID:21108628

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

2011-01-01

72

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. PMID:8120088

1994-01-01

73

Monitoring of neuronal loss in the hippocampus of A?-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis.  

PubMed

In the present study, we tried to answer the following questions: which kind of defense pathways are activated after A? insult? How defense systems react against noxious effects of A? and whether they are able to deal against apoptosis or not? So, we traced some molecular pathways including autophagy, mitophagy, and mitochondrial biogenesis before reaching to the endpoint of apoptosis. Besides, we measured the function of mitochondria after injection of A? (1-42) in CA1 area of hippocampus as a model of Alzheimer's disease (AD). Based on our data, autophagy markers reached to their maximum level and returned to the control level as apoptotic markers started to increase. As a specialized form of autophagy, mitophagy markers followed the trend of autophagy markers. Whereas mitochondrial dynamic processes shifted toward fission, mitochondrial biogenesis was severely affected by A? and significantly decreased. Alongside suppression of mitochondrial biogenesis, activity of specific enzymes involved in antioxidant defense system, electron transport chain, and tricarboxylic acid cycle (TCA) decreased in response to the A?. Activity of antioxidant enzymes increased at first and then decreased significantly compared to the control. TCA enzymes aconitase and malate dehydrogenase activities reduced immediately while citrate synthase and fumarase activities did not change. Based on our finding, monitoring of the master molecules of intracellular cascades and determining their trends before the destructive function of A? could be the target of therapeutic issues for AD. PMID:24203394

Shaerzadeh, Fatemeh; Motamedi, Fereshteh; Minai-Tehrani, Dariush; Khodagholi, Fariba

2014-03-01

74

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. PMID:24058615

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

2013-01-01

75

Nucleotide and RNA metabolism prime translational initiation in the earliest events of mitochondrial biogenesis during Arabidopsis germination.  

PubMed

Mitochondria play a crucial role in germination and early seedling growth in Arabidopsis (Arabidopsis thaliana). Morphological observations of mitochondria revealed that mitochondrial numbers, typical size, and oval morphology were evident after 12 h of imbibition in continuous light (following 48 h of stratification). The transition from a dormant to an active metabolic state was punctuated by an early molecular switch, characterized by a transient burst in the expression of genes encoding mitochondrial proteins. Factors involved in mitochondrial transcription and RNA processing were overrepresented among these early-expressed genes. This was closely followed by an increase in the transcript abundance of genes encoding proteins involved in mitochondrial DNA replication and translation. This burst in the expression of factors implicated in mitochondrial RNA and DNA metabolism was accompanied by an increase in transcripts encoding components required for nucleotide biosynthesis in the cytosol and increases in transcript abundance of specific members of the mitochondrial carrier protein family that have previously been associated with nucleotide transport into mitochondria. Only after these genes peaked in expression and largely declined were typical mitochondrial numbers and morphology observed. Subsequently, there was an increase in transcript abundance for various bioenergetic and metabolic functions of mitochondria. The coordination of nucleus- and organelle-encoded gene expression was also examined by quantitative reverse transcription-polymerase chain reaction, specifically for components of the mitochondrial electron transport chain and the chloroplastic photosynthetic machinery. Analysis of protein abundance using western-blot analysis and mass spectrometry revealed that for many proteins, patterns of protein and transcript abundance changes displayed significant positive correlations. A model for mitochondrial biogenesis during germination is proposed, in which an early increase in the abundance of transcripts encoding biogenesis functions (RNA metabolism and import components) precedes a later cascade of gene expression encoding the bioenergetic and metabolic functions of mitochondria. PMID:22345507

Law, Simon R; Narsai, Reena; Taylor, Nicolas L; Delannoy, Etienne; Carrie, Chris; Giraud, Estelle; Millar, A Harvey; Small, Ian; Whelan, James

2012-04-01

76

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

Microsoft Academic Search

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

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

2011-01-01

77

Peroxisome Proliferator-Activated-? Coactivator-1?-Mediated Mitochondrial Biogenesis Is Important for Hematopoietic Recovery in Response to Stress  

PubMed Central

Hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs) play a vital role in replenishment of blood cells. In addition to growth factors, energy metabolism plays an important role in cellular proliferation. Oxidative phosphorylation that occurs in the mitochondria is the major source of ATP. In this study, we have investigated the role of peroxisome proliferator-activated-? coactivator-1? (PGC-1?), a major regulator of mitochondrial biogenesis, in hematopoiesis. PGC-1? is expressed in HSC/HPCs. Loss of PGC-1? minimally affects basal hematopoiesis; however, it significantly impairs stress hematopoiesis. Recovery of hematopoiesis poststress involves rapid proliferation of HSC/HPCs. Growth factors stimulate HSC/HPC proliferation in a dose-dependent manner and this response is modulated by oxygen tension. Although severe hypoxic conditions inhibit HSC/HPC proliferation, mild hypoxia enhances the clonogenic potential; however, the mechanism underlying this phenomenon remains largely unknown. Our studies demonstrate that PGC-1?-mediated mitochondrial biogenesis is critical for the increased clonogenic potential of progenitors under mild hypoxia. Metabolic programming and increased glucose uptake can drive rapid progenitor cell proliferation under relatively low oxygen tension only if the HPC has the capacity to increase PGC-1? expression and mitochondrial biogenesis. Loss of PGC-1? also impairs the long-term repopulating potential of HSCs. Our findings may have therapeutic applications for rapid recovery of blood cells following myeloablation. PMID:23311338

Broxmeyer, Hal E.; Hangoc, Giao

2013-01-01

78

The transmembrane prolines of the mitochondrial ADP/ATP carrier are involved in nucleotide binding and transport and its biogenesis.  

PubMed

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. PMID:22334686

Babot, Marion; Blancard, Corinne; Pelosi, Ludovic; Lauquin, Guy J-M; Trézéguet, Véronique

2012-03-23

79

MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome.  

PubMed

Defects of the translation apparatus in human mitochondria are known to cause disease, yet details of how protein synthesis is regulated in this organelle remain to be unveiled. Ribosome production in all organisms studied thus far entails a complex, multistep pathway involving a number of auxiliary factors. This includes several RNA processing and modification steps required for correct rRNA maturation. Little is known about the maturation of human mitochondrial 16S rRNA and its role in biogenesis of the mitoribosome. Here we investigate two methyltransferases, MRM2 (also known as RRMJ2, encoded by FTSJ2) and MRM3 (also known as RMTL1, encoded by RNMTL1), that are responsible for modification of nucleotides of the 16S rRNA A-loop, an essential component of the peptidyl transferase center. Our studies show that inactivation of MRM2 or MRM3 in human cells by RNA interference results in respiratory incompetence as a consequence of diminished mitochondrial translation. Ineffective translation in MRM2- and MRM3-depleted cells results from aberrant assembly of the large subunit of the mitochondrial ribosome (mt-LSU). Our findings show that MRM2 and MRM3 are human mitochondrial methyltransferases involved in the modification of 16S rRNA and are important factors for the biogenesis and function of the large subunit of the mitochondrial ribosome. PMID:25009282

Rorbach, Joanna; Boesch, Pierre; Gammage, Payam A; Nicholls, Thomas J J; Pearce, Sarah F; Patel, Dipali; Hauser, Andreas; Perocchi, Fabiana; Minczuk, Michal

2014-09-01

80

Maternal calorie restriction modulates placental mitochondrial biogenesis and bioenergetic efficiency: putative involvement in fetoplacental growth defects in rats.  

PubMed

Low birth weight is associated with an increased risk for developing type 2 diabetes and metabolic diseases. The placental capacity to supply nutrients and oxygen to the fetus represents the main determiner of fetal growth. However, few studies have investigated the effects of maternal diet on the placenta. We explored placental adaptive proteomic processes implicated in response to maternal undernutrition. Rat term placentas from 70% food-restricted (FR30) mothers were used for a proteomic screen. Placental mitochondrial functions were evaluated using molecular and functional approaches, and ATP production was measured. FR30 drastically reduced placental and fetal weights. FR30 placentas displayed 14 proteins that were differentially expressed, including several mitochondrial proteins. FR30 induced a marked increase in placental mtDNA content and changes in mitochondrial functions, including modulation of the expression of genes implicated in biogenesis and bioenergetic pathways. FR30 mitochondria showed higher oxygen consumption but failed to maintain their ATP production. Maternal undernutrition induces placental mitochondrial abnormalities. Although an increase in biogenesis and bioenergetic efficiency was noted, placental ATP level was reduced. Our data suggest that placental mitochondrial defects may be implicated in fetoplacental pathologies. PMID:23092912

Mayeur, Sylvain; Lancel, Steve; Theys, Nicolas; Lukaszewski, Marie-Amélie; Duban-Deweer, Sophie; Bastide, Bruno; Hachani, Johan; Cecchelli, Roméo; Breton, Christophe; Gabory, Anne; Storme, Laurent; Reusens, Brigitte; Junien, Claudine; Vieau, Didier; Lesage, Jean

2013-01-01

81

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. PMID:19559056

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

2009-01-01

82

?-SNAP inhibits AMPK signaling to reduce mitochondrial biogenesis and dephosphorylates Thr172 in AMPK? in vitro  

PubMed Central

The AMP-activated protein kinase (AMPK) regulates metabolism in normal and pathological conditions and responds to nutrients, hormones, anti-diabetic drugs and physical exercise. AMPK is activated by kinase LKB1 and inactivated by phosphatases whose identities remain uncertain. Here we show that AMPK associates with ?-SNAP, an adapter that enables disassembly of cis-SNARE complexes formed during membrane fusion. Knockdown of ?-SNAP activates AMPK to phosphorylate its endogenous substrates ACC and Raptor and provokes mitochondrial biogenesis. AMPK phosphorylation is rescued from ?-SNAP RNAi by LKB1 knockdown or expression of wild type but not mutated ?-SNAP. Recombinant wild type but not mutated ?-SNAP dephosphorylates pThr172 in AMPK? in vitro. Over-expression of wild-type but not mutated ?-SNAP prevents AMPK activation in cells treated with agents to elevate AMP concentration. The mouse ?-SNAP mutant hyh (hydrocephalus with hop gait) shows enhanced binding and inhibition of AMPK. By negatively controlling AMPK, ?-SNAP therefore potentially coordinates membrane trafficking and metabolism. PMID:23463002

Wang, Lifu; Brautigan, David L.

2013-01-01

83

Role of Phosphatidylethanolamine in the Biogenesis of Mitochondrial Outer Membrane Proteins*  

PubMed Central

The mitochondrial outer membrane contains proteinaceous machineries for the import and assembly of proteins, including TOM (translocase of the outer membrane) and SAM (sorting and assembly machinery). It has been shown that the dimeric phospholipid cardiolipin is required for the stability of TOM and SAM complexes and thus for the efficient import and assembly of ?-barrel proteins and some ?-helical proteins of the outer membrane. Here, we report that mitochondria deficient in phosphatidylethanolamine (PE), the second non-bilayer-forming phospholipid, are impaired in the biogenesis of ?-barrel proteins, but not of ?-helical outer membrane proteins. The stability of TOM and SAM complexes is not disturbed by the lack of PE. By dissecting the import steps of ?-barrel proteins, we show that an early import stage involving translocation through the TOM complex is affected. In PE-depleted mitochondria, the TOM complex binds precursor proteins with reduced efficiency. We conclude that PE is required for the proper function of the TOM complex. PMID:23625917

Becker, Thomas; Horvath, Susanne E.; Bottinger, Lena; Gebert, Natalia; Daum, Gunther; Pfanner, Nikolaus

2013-01-01

84

Alternative function for the mitochondrial SAM complex in biogenesis of alpha-helical TOM proteins.  

PubMed

The mitochondrial outer membrane contains two preprotein translocases: the general translocase of outer membrane (TOM) and the beta-barrel-specific sorting and assembly machinery (SAM). TOM functions as the central entry gate for nuclear-encoded proteins. The channel-forming Tom40 is a beta-barrel protein, whereas all Tom receptors and small Tom proteins are membrane anchored by a transmembrane alpha-helical segment in their N- or C-terminal portion. Synthesis of Tom precursors takes place in the cytosol, and their import occurs via preexisting TOM complexes. The precursor of Tom40 is then transferred to SAM for membrane insertion and assembly. Unexpectedly, we find that the biogenesis of alpha-helical Tom proteins with a membrane anchor in the C-terminal portion is SAM dependent. Each SAM protein is necessary for efficient membrane integration of the receptor Tom22, whereas assembly of the small Tom proteins depends on Sam37. Thus, the substrate specificity of SAM is not restricted to beta-barrel proteins but also includes the majority of alpha-helical Tom proteins. PMID:18039934

Stojanovski, Diana; Guiard, Bernard; Kozjak-Pavlovic, Vera; Pfanner, Nikolaus; Meisinger, Chris

2007-12-01

85

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

2012-02-01

86

Melatonin Improves Mitochondrial Function by Promoting MT1/SIRT1/PGC-1 Alpha-Dependent Mitochondrial Biogenesis in Cadmium-Induced Hepatotoxicity In Vitro  

PubMed Central

Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10?M) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity. PMID:25159133

Guo, Pan; Pi, Huifeng; Xu, Shangcheng; Zhang, Lei; Li, Yuming; Li, Min; Cao, Zhengwang; Tian, Li; Xie, Jia; Li, Renyan; He, Mindi; Lu, Yonghui; Liu, Chuan; Duan, Weixia; Yu, Zhengping; Zhou, Zhou

2014-01-01

87

Melatonin Improves Mitochondrial Function by Promoting MT1/SIRT1/PGC-1 Alpha-Dependent Mitochondrial Biogenesis in Cadmium-Induced Hepatotoxicity In Vitro.  

PubMed

Melatonin is an indolamine synthesized in the pineal gland that has a wide range of physiological functions, and it has been under clinical investigation for expanded applications. Increasing evidence demonstrates that melatonin can ameliorate cadmium-induced hepatotoxicity. However, the potentially protective effects of melatonin against cadmium-induced hepatotoxicity and the underlying mechanisms of this protection remain unclear. This study investigates the protective effects of melatonin pretreatment on cadmium-induced hepatotoxicity and elucidates the potential mechanism of melatonin-mediated protection. We exposed HepG2 cells to different concentrations of cadmium chloride (2.5, 5, and 10?M) for 12 h. We found that Cd stimulated cytotoxicity, disrupted the mitochondrial membrane potential, increased reactive oxygen species production, and decreased mitochondrial mass and mitochondrial DNA content. Consistent with this finding, Cd exposure was associated with decreased Sirtuin 1 (SIRT1) protein expression and activity, thus promoted acetylation of PGC-1 alpha, a key enzyme involved in mitochondrial biogenesis and function, although Cd did not disrupt the interaction between SIRT1 and PGC-1 alpha. However, all cadmium-induced mitochondrial oxidative injuries were efficiently attenuated by melatonin pretreatment. Moreover, Sirtinol and SIRT1 siRNA each blocked the melatonin-mediated elevation in mitochondrial function by inhibiting SIRT1/ PGC-1 alpha signaling. Luzindole, a melatonin receptor antagonist, was found to partially block the ability of melatonin to promote SIRT1/ PGC-1 alpha signaling. In summary, our results indicate that SIRT1 plays an essential role in the ability of moderate melatonin to stimulate PGC-1 alpha and improve mitochondrial biogenesis and function at least partially through melatonin receptors in cadmium-induced hepatotoxicity. PMID:25159133

Guo, Pan; Pi, Huifeng; Xu, Shangcheng; Zhang, Lei; Li, Yuming; Li, Min; Cao, Zhengwang; Tian, Li; Xie, Jia; Li, Renyan; He, Mindi; Lu, Yonghui; Liu, Chuan; Duan, Weixia; Yu, Zhengping; Zhou, Zhou

2014-11-01

88

Acetyl l-carnitine feeding to unloaded rats triggers in soleus muscle the coordinated expression of genes involved in mitochondrial biogenesis  

Microsoft Academic Search

The expressional profile of mitochondrial transcripts and of genes involved in the mitochondrial biogenesis pathway induced by ALCAR daily supplementation in soleus muscle of control and unloaded 3-month-old rats has been analyzed. It has been found that ALCAR treatment is able to upregulate the expression level of mitochondrial transcripts (COX I, ATP6, ND6, 16 S rRNA) in both control and unloaded

P. Cassano; A. G. Sciancalepore; V. Pesce; M. Flück; H. Hoppeler; M. Calvani; L. Mosconi; P. Cantatore; M. N. Gadaleta

2006-01-01

89

Decreased Levels of Proapoptotic Factors and Increased Key Regulators of Mitochondrial Biogenesis Constitute New Potential Beneficial Features of Long-lived Growth Hormone Receptor Gene–Disrupted Mice  

PubMed Central

Decreased somatotrophic signaling is among the most important mechanisms associated with extended longevity. Mice homozygous for the targeted disruption of the growth hormone (GH) receptor gene (GH receptor knockout; GHRKO) are obese and dwarf, are characterized by a reduced weight and body size, undetectable levels of GH receptor, high concentration of serum GH, and greatly reduced plasma levels of insulin and insulin-like growth factor-I, and are remarkably long lived. Recent results suggest new features of GHRKO mice that may positively affect longevity—decreased levels of proapoptotic factors and increased levels of key regulators of mitochondrial biogenesis. The alterations in levels of the proapoptotic factors and key regulators of mitochondrial biogenesis were not further improved by two other potential life-extending interventions—calorie restriction and visceral fat removal. This may attribute the primary role to GH resistance in the regulation of apoptosis and mitochondrial biogenesis in GHRKO mice in terms of increased life span. PMID:23197187

2013-01-01

90

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. PMID:24167412

Oh, Young J.

2013-01-01

91

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  

SciTech Connect

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. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

2012-10-15

92

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.

Hagland, Hanne R.; Nilsson, Linn I.H. [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Burri, Lena [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway)] [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Nikolaisen, Julie [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Berge, Rolf K. [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway) [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Department of Heart Disease, Haukeland University Hospital (Norway); Tronstad, Karl J., E-mail: karl.tronstad@biomed.uib.no [Department of Biomedicine, University of Bergen (Norway)

2013-01-11

93

Exercise-induced asthma.  

PubMed

Exercise-induced asthma is the phenomenon of transient airflow obstruction, typically 5 to 15 minutes after physical exertion. The increased airway resistance produces a 15% or greater decrease in the forced expiratory volume in 1 second, or in peak expiratory flow rate. Exercise-induced asthma occurs in 90% of individuals with asthma, representing 12% to 15% of the population world-wide. The prevalence of exercise-induced asthma among athletes ranges between 3% and 11%. Several theories of the etiology exist: respiratory heat or water loss (or both), hyperventilation causing discharge of bronchospastic chemical mediators or rebound rewarming of the blood in airway tissues. Treatment is either by pharmacologic or nonpharmacologic means, but medication continues to be the cornerstone of therapy for exercise-induced asthma. beta 2-Specific agonists remain the drugs of choice. Cromolyn sodium and nedocromil sodium are alternatives to the beta 2-agonists, and the combined use of the two classes of agents can provide additive benefits. PMID:9594485

Wilkerson, L A

1998-04-01

94

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

95

Exercise-induced asthma  

Microsoft Academic Search

Exercise-induced asthma (EIA) is common in asthmatic children and adolescents. Since it may cause limitations to daily life activities in up to 30%, mastering EIA is important in asthma management.EIA consists of bronchial obstruction occurring immediately, or soon after, physical exercise as a result of increased respiratory water and heat loss due to increased ventilation during exercise, with the subsequent

Kai-Håkon Carlsen; Karin C. L Carlsen

2002-01-01

96

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. PMID:22390282

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

2012-01-01

97

Assessment of Newly Synthesized Mitochondrial DNA Using BrdU Labeling in Primary Neurons from Alzheimer's Disease Mice: Implications for Impaired Mitochondrial Biogenesis and Synaptic Damage  

PubMed Central

The purpose our study was to assess mitochondrial biogenesis and distribution in murine primary neurons. Using 5-bromo-2-deoxyuridie (BrdU) incorporation and primary neurons, we studied the mitochondrial biogenesis and mitochondrial distribution in hippocampal neurons from amyloid beta precursor protein (A?PP) transgenic mice and wild-type (WT) neurons treated with oxidative stressors, rotenone and H2O2. We found that after 20 hr of labeling, BrdU incorporation was specific to porin-positive mitochondria. The proportion of mitochondrial area that labeled with BrdU was 40.3 ± 6.3% at 20 hr. The number of mitochondria with newly synthesized DNA was higher in A?PP neuronal cell bodies than in the cell bodies of WT neurons (A?PP, 45.23 ± 2.67 BrdU-positive/cell body; WT, 32.92 ± 2.49 BrdU-positive/cell body; p = 0.005). In neurites, the number of BrdU-positive mitochondria decreased in A?PP cultures compared to WT neurons (A?PP, 0.105 ± 0.008 BrdU-positive/?m neurite; WT, 0.220 ± 0.036 BrdU-positive?/??m neurite; p = 0.010). Further, BrdU in the cell body increased when neurons were treated with low doses of H2O2 (49.6 ± 2.7 BrdU-positive/cell body, p = 0.0002 compared to untreated cells), while the neurites showed decreased BrdU staining (0.122 ± 0.010 BrdU-positive/?m neurite, p = 0.005 compared to the untreated). BrdU labeling was increased in the cell body under rotenone treatment. Additionally, under rotenone treatment, the content of BrdU labeling decreased in neurites. These findings suggest that A? and mitochondrial toxins enhance mitochondrial fragmentation in cell body, and may cause impaired axonal transport of mitochondria leading to synaptic degeneration. PMID:21549836

Calkins, Marcus J.; Reddy, P. Hemachandra

2011-01-01

98

Tim50a, a nuclear isoform of the mitochondrial Tim50, interacts with proteins involved in snRNP biogenesis  

PubMed Central

Background The Cajal body (CB) is a nuclear suborganelle involved in the biogenesis of small nuclear ribonucleoproteins (snRNPs), which are vital for pre-mRNA splicing. Newly imported Sm-class snRNPs traffic through CBs, where the snRNA component of the snRNP is modified, and then target to other nuclear domains such as speckles and perichromatin fibrils. It is not known how nascent snRNPs localize to the CB and are released from this structure after modification. The marker protein for CBs, coilin, may play a role in snRNP biogenesis given that it can interact with snRNPs and SMN, the protein mutated in Spinal Muscular Atrophy. Loss of coilin function in mice leads to significant viability and fertility problems and altered CB formation. Results In this report, we identify a minor isoform of the mitochondrial Tim50, Tim50a, as a coilin interacting protein. The Tim50a transcript can be detected in some cancer cell lines and normal brain tissue. The Tim50a protein differs only from Tim50 in that it contains an additional 103 aa N-terminal to the translation start of Tim50. Importantly, a putative nuclear localization signal is found within these 103 residues. In contrast to Tim50, which localizes to the cytoplasm and mitochondria, Tim50a is strictly nuclear and is enriched in speckles with snRNPs. In addition to coilin, Tim50a interacts with snRNPs and SMN. Competition binding experiments demonstrate that coilin competes with Sm proteins of snRNPs and SMN for binding sites on Tim50a. Conclusion Tim50a may play a role in snRNP biogenesis given its cellular localization and protein interaction characteristics. We hypothesize that Tim50a takes part in the release of snRNPs and SMN from the CB. PMID:16008839

Xu, Hongzhi; Somers, Z Brad; Robinson, Melvin L; Hebert, Michael D

2005-01-01

99

Role of calcium and AMP kinase in the regulation of mitochondrial biogenesis and GLUT4 levels in muscle.  

PubMed

Contractile activity induces mitochondrial biogenesis and increases glucose transport capacity in muscle. There has been much research on the mechanisms responsible for these adaptations. The present paper reviews the evidence, which indicates that the decrease in the levels of high-energy phosphates, leading to activation of AMP kinase (AMPK), and the increase in cytosolic Ca(2+), which activates Ca(2+)/calmodulin-dependent protein kinase (CAMK), are signals that initiate these adaptative responses. Although the events downstream of AMPK and CAMK have not been well characterized, these events lead to activation of various transcription factors, including: nuclear respiratory factors (NRF) 1 and 2, which cause increased expression of proteins of the respiratory chain; PPAR-alpha, which up regulates the levels of enzymes of beta oxidation; mitochondrial transcription factor A, which activates expression of the mitochondrial genome; myocyte-enhancing factor 2A, the transcription factor that regulates GLUT4 expression. The well-orchestrated expression of the multitude of proteins involved in these adaptations is mediated by the rapid activation of PPAR gamma co-activator (PGC) 1, a protein that binds to various transcription factors to maximize transcriptional activity. Activating AMPK using 5-aminoimidizole-4-carboxamide-1-beta-D-riboside (AICAR) and increasing cytoplasmic Ca(2+) using caffeine, W7 or ionomycin in L6 myotubes increases the concentration of mitochondrial enzymes and GLUT4 and enhances the binding of NRF-1 and NRF-2 to DNA. AICAR and Ca-releasing agents also increase the levels of PGC-1, mitochondrial transcription factor A and myocyte-enhancing factors 2A and 2D. These results are similar to the responses seen in muscle during the adaptation to endurance exercise and show that L6 myotubes are a suitable model for studying the mechanisms by which exercise causes the adaptive responses in muscle mitochondria and glucose transport. PMID:15294043

Ojuka, Edward O

2004-05-01

100

Exercise-induced rhabdomyolysis.  

PubMed

Exercise-induced rhabdomyolysis, or exertional rhabdomyolysis (ER), is a clinical entity typically considered when someone presents with muscle stiffness, swelling, and pain out of proportion to the expected fatigue post exercise. The diagnosis is confirmed by myoglobinuria, and an elevated serum Creatinine Phosphokinase (CPK) level, usually 10 times the normal range. However, an elevation in CPK is seen in most forms of strenuous exercise, up to 20 times the upper normal range. Therefore, there is no definitive pathologic CPK cut-off. Fortunately the dreaded complication of acute renal failure is rare compared to other forms rhabdomyolysis. We review the risks, diagnosis, clinical course and treatment for exercise- induced rhabdomyolysis. [Full text available at http://rimed.org/rimedicaljournal-2014-11.asp, free with no login]. PMID:25365815

Lee, George

2014-01-01

101

Exercise-induced bronchoconstriction.  

PubMed

Exercise-induced bronchoconstriction (EIB) occurs commonly in patients with asthma but also can affect individuals without asthma. EIB is particularly common in populations of athletes. Common symptoms include cough, dyspnea, chest tightness, and wheezing; however, there can be a variety of more subtle symptoms. In this article, the clinical presentation of EIB as well as the diagnosis and treatment of EIB are outlined. PMID:24286685

Parsons, Jonathan P

2014-02-01

102

Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators, tricarboxylic Acid cycle activity and exacerbates recognition memory deficit in rat model of Alzheimer's disease.  

PubMed

3-Methyladenine (3-MA), as a PI3K inhibitor, is widely used for inhibition of autophagy. Inhibition of PI3K class I leads to inhibition of Akt phosphorylation, a central molecule involved in diverse arrays of intracellular cascades in nervous system. Accordingly, in the present study, we aimed to determine the alterations of specific mitochondrial biogenesis markers and mitochondrial function in 3-MA-injected rats following amyloid beta (A?) insult. Our data revealed that inhibition of Akt phosphorylation downregulates master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?). Our data also showed that decrease in PGC-1? level presumably is due to decrease in the phosphorylation of cAMP-response element binding and AMP-activated kinase, two upstream activators of PGC-1?. As a consequence, the level of some mitochondrial biogenesis factors including nuclear respiratory factor-1, mitochondrial transcription factor A, and Cytochrome c decreased significantly. Also, activities of tricarboxylic acid cycle (TCA) enzymes such as Aconitase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reduced in the presence of 3-MA with or without A? insult. Decrease in mitochondrial biogenesis factors and TCA enzyme activity in the rats receiving 3-MA and A? were more compared to the rats that received either alone; indicating the additive destructive effects of these two agents. In agreement with our molecular results, data obtained from behavioral test (using novel objective recognition test) indicated that inhibition of Akt phosphorylation with or without A? injection impaired novel recognition (non-spatial) memory. Our results suggest that 3-MA amplified deleterious effects of A? by targeting central molecule Akt. PMID:25135709

Shaerzadeh, Fatemeh; Motamedi, Fereshteh; Khodagholi, Fariba

2014-11-01

103

Biogenesis of the mitochondrial Tom40 channel in skeletal muscle from aged animals and its adaptability to chronic contractile activity.  

PubMed

Evidence exists that mitochondrial content and/or function is reduced in muscle of aging individuals. The purposes of this study were to investigate the contribution of outer membrane protein import and assembly processes to this decline and to determine whether the assembly process could adapt to chronic contractile activity (CCA). Tom40 assembly into the translocases of the outer membrane (TOM complex) was measured in subsarcolemmal mitochondria obtained from young (6 mo old) and aged (36 mo old) Fischer 344 x Brown Norway animals. While the initial import of Tom40 did not differ between young and aged animals, its subsequent assembly into the final approximately 380 kDa complex was 2.2-fold higher (P < 0.05) in mitochondria from aged compared with young animals. This was associated with a higher abundance of Tom22, a protein vital for the assembly process. CCA induced a greater initial import and subsequent assembly of Tom40 in mitochondria from young animals, resulting in a CCA-induced 75% increase (P < 0.05) in Tom40 within mitochondria. This effect of CCA was attenuated in mitochondria from old animals. These data suggest that the import and assembly of proteins into the outer membrane do not contribute to reduced mitochondrial content or function in aged animals. Indeed, the greater assembly rate in mitochondria from aged animals may be a compensatory mechanism attempting to offset any decrements in mitochondrial content or function within aged muscle. Our data also indicate the potential of CCA to contribute to increased mitochondrial biogenesis in muscle through changes in the outer membrane import and assembly pathway. PMID:20107041

Joseph, Anna-Maria; Ljubicic, Vladimir; Adhihetty, Peter J; Hood, David A

2010-06-01

104

CREB-1? Is Recruited to and Mediates Upregulation of the Cytochrome c Promoter during Enhanced Mitochondrial Biogenesis Accompanying Skeletal Muscle Differentiation? †  

PubMed Central

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 nucleus-encoded cytochrome c, cytochrome c oxidase subunit IV, and mitochondrial transcription factor A (TFAM) increased, together with total cellular RNA and protein levels. Detailed analysis of the cytochrome c promoter by luciferase reporter, binding affinity, and electrophoretic mobility shift assays as well as mutagenesis studies revealed a critical role for cyclic AMP responsive element binding protein 1 (CREB-1) for promoter activation. Expression of two CREB-1 isoforms was observed by using specific antibodies and quantitative reverse transcription-PCR, and a shift from phosphorylated CREB-1? in myoblasts to phosphorylated CREB-1? protein in myotubes was shown, while mRNA ratios remained unchanged. Chromatin immunoprecipitation assays confirmed preferential binding of CREB-1? in situ to the cytochrome c promoter in myotubes. Overexpression of constitutively active and dominant-negative forms supported the key role of CREB-1 in regulating the expression of genes encoding mitochondrial proteins during myogenesis and probably also in other situations of enhanced mitochondrial biogenesis. PMID:18227154

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

2008-01-01

105

Dietary wolfberry up-regulates carotenoid metabolic genes and enhances mitochondrial biogenesis in the retina of db/db diabetic mice  

PubMed Central

Scope Our aim was to investigate whether dietary wolfberry altered carotenoid metabolic gene expression and enhanced mitochondrial biogenesis in the retina of diabetic mice. Methods and Results Six-week-old male db/db and wild type mice were fed the control or wolfberry diets for 8 weeks. At study termination, liver and retinal tissues were collected for analysis by transmission electron microscopy, real-time PCR, immunoprecipitation, Western blot, and HPLC. Wolfberry elevated zeaxanthin and lutein levels in the liver and retinal tissues and stimulated expression of retinal scavenger receptor class B type I, glutathione S-transferase Pi 1, and ?,?-carotene 9’,10’-oxygenase 2, and induced activation and nuclear enrichment of retinal AMP-activated protein kinase ?2 (AMPK?2). Furthermore, wolfberry attenuated hypoxia and mitochondrial stress as demonstrated by declined expression of hypoxia-inducible factor-1?, vascular endothelial growth factor, and heat shock protein 60. Wolfberry enhanced retinal mitochondrial biogenesis in diabetic retinas as demonstrated by reversed mitochondrial dispersion in the retinal pigment epithelium, increased mitochondrial copy number, elevated citrate synthase activity, and up-regulated expression of peroxisome proliferator-activated receptor ? co-activator 1 ?, nuclear respiratory factor 1, and mitochondrial transcription factor A. Conclusion Consumption of dietary wolfberry could be beneficial to retinoprotection through reversal of mitochondrial function in diabetic mice. PMID:23505020

Yu, Huifeng; Wark, Logan; Ji, Hua; Willard, Lloyd; Jaing, Yu; Han, Jing; He, Hui; Ortiz, Edlin; Zhang, Yunong; Medeiros, Denis M; Lin, Dingbo

2013-01-01

106

Elevated Mitochondrial Oxidative Stress Impairs Metabolic Adaptations to Exercise in Skeletal Muscle  

PubMed Central

Mitochondrial oxidative stress is a complex phenomenon that is inherently tied to energy provision and is implicated in many metabolic disorders. Exercise training increases mitochondrial oxidative capacity in skeletal muscle yet it remains unclear if oxidative stress plays a role in regulating these adaptations. We demonstrate that the chronic elevation in mitochondrial oxidative stress present in Sod2+/- mice impairs the functional and biochemical mitochondrial adaptations to exercise. Following exercise training Sod2+/- mice fail to increase maximal work capacity, mitochondrial enzyme activity and mtDNA copy number, despite a normal augmentation of mitochondrial proteins. Additionally, exercised Sod2+/- mice cannot compensate for their higher amount of basal mitochondrial oxidative damage and exhibit poor electron transport chain complex assembly that accounts for their compromised adaptation. Overall, these results demonstrate that chronic skeletal muscle mitochondrial oxidative stress does not impact exercise induced mitochondrial biogenesis, but impairs the resulting mitochondrial protein function and can limit metabolic plasticity. PMID:24324727

Crane, Justin D.; Abadi, Arkan; Hettinga, Bart P.; Ogborn, Daniel I.; MacNeil, Lauren G.; Steinberg, Gregory R.; Tarnopolsky, Mark A.

2013-01-01

107

Cardiomyocyte-Restricted Deletion of PPAR?/? in PPAR?-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation  

PubMed Central

It is well documented that PPAR? and PPAR?/? share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPAR?/? deficiency in mice leads to severe cardiac pathological development, whereas global PPAR? knockout shows a benign cardiac phenotype. It is unknown whether a PPAR?-null background would alter the pathological development in mice with cardiomyocyte-restricted PPAR?/? deficiency. In the present study, a mouse model with long-term PPAR?/? deficiency in PPAR?-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPAR?-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPAR?/? deficiency. Moreover, PPAR?-null did not alter the phenotypic development in adult mice with the short-term deletion of PPAR?/? in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPAR?/? in PPAR?-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPAR?/? is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPAR?. PMID:21904539

Liu, Jian; Wang, Peiyong; He, Lan; Li, Yuquan; Luo, Jinwen; Cheng, Lihong; Qin, Qianhong; Brako, Lawrence A.; Lo, Woo-kuen; Lewis, William; Yang, Qinglin

2011-01-01

108

Cardiomyocyte-Restricted Deletion of PPAR?/? in PPAR?-Null Mice Causes Impaired Mitochondrial Biogenesis and Defense, but No Further Depression of Myocardial Fatty Acid Oxidation.  

PubMed

It is well documented that PPAR? and PPAR?/? share overlapping functions in regulating myocardial lipid metabolism. However, previous studies demonstrated that cardiomyocyte-restricted PPAR?/? deficiency in mice leads to severe cardiac pathological development, whereas global PPAR? knockout shows a benign cardiac phenotype. It is unknown whether a PPAR?-null background would alter the pathological development in mice with cardiomyocyte-restricted PPAR?/? deficiency. In the present study, a mouse model with long-term PPAR?/? deficiency in PPAR?-null background showed a comparably reduced cardiac expression of lipid metabolism to those of single PPAR-deficient mouse models. The PPAR?-null background did not rescue or aggravate the cardiac pathological development linked to cardiomyocyte-restricted PPAR?/? deficiency. Moreover, PPAR?-null did not alter the phenotypic development in adult mice with the short-term deletion of PPAR?/? in their hearts, which showed mitochondrial abnormalities, depressed cardiac performance, and cardiac hypertrophy with attenuated expression of key factors in mitochondrial biogenesis and defense. The present study demonstrates that cardiomyocyte-restricted deletion of PPAR?/? in PPAR?-null mice causes impaired mitochondrial biogenesis and defense, but no further depression of fatty acid oxidation. Therefore, PPAR?/? is essential for maintaining mitochondrial biogenesis and defense in cardiomyocytes independent of PPAR?. PMID:21904539

Liu, Jian; Wang, Peiyong; He, Lan; Li, Yuquan; Luo, Jinwen; Cheng, Lihong; Qin, Qianhong; Brako, Lawrence A; Lo, Woo-Kuen; Lewis, William; Yang, Qinglin

2011-01-01

109

Agonism of the 5-hydroxytryptamine 1F receptor promotes mitochondrial biogenesis and recovery from acute kidney injury.  

PubMed

Many acute and chronic conditions, such as acute kidney injury, chronic kidney disease, heart failure, and liver disease, involve mitochondrial dysfunction. Although we have provided evidence that drug-induced stimulation of mitochondrial biogenesis (MB) accelerates mitochondrial and cellular repair, leading to recovery of organ function, only a limited number of chemicals have been identified that induce MB. The goal of this study was to assess the role of the 5-hydroxytryptamine 1F (5-HT1F) receptor in MB. Immunoblot and quantitative polymerase chain reaction analyses revealed 5-HT1F receptor expression in renal proximal tubule cells (RPTC). A MB screening assay demonstrated that two selective 5-HT1F receptor agonists, LY334370 (4-fluoro-N-[3-(1-methyl-4-piperidinyl)-1H-indol-5-yl]benzamide) and LY344864 (N-[(3R)-3-(dimethylamino)-2,3,4,9-tetrahydro-1H-carbazol-6-yl]-4-fluorobenzamide; 1-100 nM) increased carbonylcyanide-p-trifluoromethoxyphenylhydrazone-uncoupled oxygen consumption in RPTC, and validation studies confirmed both agonists increased mitochondrial proteins [e.g., ATP synthase ?, cytochrome c oxidase 1 (Cox1), and NADH dehydrogenase (ubiquinone) 1? subcomplex subunit 8 (NDUFB8)] in vitro. Small interfering RNA knockdown of the 5-HT1F receptor blocked agonist-induced MB. Furthermore, LY344864 increased peroxisome proliferator-activated receptor coactivator 1-?, Cox1, and NDUFB8 transcript levels and mitochondrial DNA (mtDNA) copy number in murine renal cortex, heart, and liver. Finally, LY344864 accelerated recovery of renal function, as indicated by decreased blood urea nitrogen and kidney injury molecule 1 and increased mtDNA copy number following ischemia/reperfusion-induced acute kidney injury (AKI). In summary, these studies reveal that the 5-HT1F receptor is linked to MB, 5-HT1F receptor agonism promotes MB in vitro and in vivo, and 5-HT1F receptor agonism promotes recovery from AKI injury. Induction of MB through 5-HT1F receptor agonism represents a new target and approach to treat mitochondrial organ dysfunction. PMID:24849926

Garrett, Sara M; Whitaker, Ryan M; Beeson, Craig C; Schnellmann, Rick G

2014-08-01

110

Nucleotide and RNA Metabolism Prime Translational Initiation in the Earliest Events of Mitochondrial Biogenesis during Arabidopsis Germination1[W][OA  

PubMed Central

Mitochondria play a crucial role in germination and early seedling growth in Arabidopsis (Arabidopsis thaliana). Morphological observations of mitochondria revealed that mitochondrial numbers, typical size, and oval morphology were evident after 12 h of imbibition in continuous light (following 48 h of stratification). The transition from a dormant to an active metabolic state was punctuated by an early molecular switch, characterized by a transient burst in the expression of genes encoding mitochondrial proteins. Factors involved in mitochondrial transcription and RNA processing were overrepresented among these early-expressed genes. This was closely followed by an increase in the transcript abundance of genes encoding proteins involved in mitochondrial DNA replication and translation. This burst in the expression of factors implicated in mitochondrial RNA and DNA metabolism was accompanied by an increase in transcripts encoding components required for nucleotide biosynthesis in the cytosol and increases in transcript abundance of specific members of the mitochondrial carrier protein family that have previously been associated with nucleotide transport into mitochondria. Only after these genes peaked in expression and largely declined were typical mitochondrial numbers and morphology observed. Subsequently, there was an increase in transcript abundance for various bioenergetic and metabolic functions of mitochondria. The coordination of nucleus- and organelle-encoded gene expression was also examined by quantitative reverse transcription-polymerase chain reaction, specifically for components of the mitochondrial electron transport chain and the chloroplastic photosynthetic machinery. Analysis of protein abundance using western-blot analysis and mass spectrometry revealed that for many proteins, patterns of protein and transcript abundance changes displayed significant positive correlations. A model for mitochondrial biogenesis during germination is proposed, in which an early increase in the abundance of transcripts encoding biogenesis functions (RNA metabolism and import components) precedes a later cascade of gene expression encoding the bioenergetic and metabolic functions of mitochondria. PMID:22345507

Law, Simon R.; Narsai, Reena; Taylor, Nicolas L.; Delannoy, Etienne; Carrie, Chris; Giraud, Estelle; Millar, A. Harvey; Small, Ian; Whelan, James

2012-01-01

111

Acute exercise induces tumour suppressor protein p53 translocation to the mitochondria and promotes a p53-Tfam-mitochondrial DNA complex in skeletal muscle.  

PubMed

The major tumour suppressor protein p53 plays an important role in maintaining mitochondrial content and function in skeletal muscle. p53 has been shown to reside in the mitochondria complexed with mitochondrial DNA (mtDNA); however, the physiological repercussions of mitochondrial p53 remain unknown. We endeavoured to elucidate whether an acute bout of endurance exercise could mediate an increase in mitochondrial p53 levels. C57Bl6 mice (n = 6 per group) were randomly assigned to sedentary, acute exercise (AE, 15 m min(-1) for 90 min) or acute exercise + 3 h recovery (AER) groups. Exercise concomitantly increased the mRNA content of nuclear-encoded (PGC-1?, Tfam, NRF-1, COX-IV, citrate synthase) and mtDNA-encoded (COX-I) genes in the AE group, and further by ?5-fold in the AER group. Nuclear p53 protein levels were reduced in the AE and AER groups, while in contrast, the abundance of p53 was drastically enhanced by ?2.4-fold and ?3.9-fold in subsarcolemmal and intermyofibrillar mitochondria, respectively, in the AER conditions. Within the mitochondria, the interaction of p53 with mtDNA at the D-loop and with Tfam was elevated by ?4.6-fold and ?3.6-fold, respectively, in the AER group. In the absence of p53, the enhanced COX-I mRNA content observed with AE and AER was abrogated. This study is the first to indicate that endurance exercise can signal to localize p53 to the mitochondria where it may serve to positively modulate the activity of the mitochondrial transcription factor Tfam. Our findings help us understand the mechanisms underlying the effects of exercise as a therapeutic intervention designed to trigger the pro-metabolic functions of p53. PMID:23690562

Saleem, Ayesha; Hood, David A

2013-07-15

112

Biogenesis of the mitochondrial TOM complex: Mim1 promotes insertion and assembly of signal-anchored receptors.  

PubMed

The translocase of the outer membrane (TOM complex) is the central entry gate for nuclear-encoded mitochondrial precursor proteins. All Tom proteins are also encoded by nuclear genes and synthesized as precursors in the cytosol. The channel-forming beta-barrel protein Tom40 is targeted to mitochondria via Tom receptors and inserted into the outer membrane by the sorting and assembly machinery (SAM complex). A further outer membrane protein, Mim1, plays a less defined role in assembly of Tom40 into the TOM complex. The three receptors Tom20, Tom22, and Tom70 are anchored in the outer membrane by a single transmembrane alpha-helix, located at the N terminus in the case of Tom20 and Tom70 (signal-anchored) or in the C-terminal portion in the case of Tom22 (tail-anchored). Insertion of the precursor of Tom22 into the outer membrane requires pre-existing Tom receptors while the import pathway of the precursors of Tom20 and Tom70 is only poorly understood. We report that Mim1 is required for efficient membrane insertion and assembly of Tom20 and Tom70, but not Tom22. We show that Mim1 associates with SAM(core) components to a large SAM complex, explaining its role in late steps of the assembly pathway of Tom40. We conclude that Mim1 is not only required for biogenesis of the beta-barrel protein Tom40 but also for membrane insertion and assembly of signal-anchored Tom receptors. Thus, Mim1 plays an important role in the efficient assembly of the mitochondrial TOM complex. PMID:17974559

Becker, Thomas; Pfannschmidt, Sylvia; Guiard, Bernard; Stojanovski, Diana; Milenkovic, Dusanka; Kutik, Stephan; Pfanner, Nikolaus; Meisinger, Chris; Wiedemann, Nils

2008-01-01

113

Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet.  

PubMed

We measured the effects of a diet in which D-?-hydroxybutyrate-(R)-1,3 butanediol monoester [ketone ester (KE)] replaced equicaloric amounts of carbohydrate on 8-wk-old male C57BL/6J mice. Diets contained equal amounts of fat, protein, and micronutrients. The KE group was fed ad libitum, whereas the control (Ctrl) mice were pair-fed to the KE group. Blood d-?-hydroxybutyrate levels in the KE group were 3-5 times those reported with high-fat ketogenic diets. Voluntary food intake was reduced dose dependently with the KE diet. Feeding the KE diet for up to 1 mo increased the number of mitochondria and doubled the electron transport chain proteins, uncoupling protein 1, and mitochondrial biogenesis-regulating proteins in the interscapular brown adipose tissue (IBAT). [(18)F]-Fluorodeoxyglucose uptake in IBAT of the KE group was twice that in IBAT of the Ctrl group. Plasma leptin levels of the KE group were more than 2-fold those of the Ctrl group and were associated with increased sympathetic nervous system activity to IBAT. The KE group exhibited 14% greater resting energy expenditure, but the total energy expenditure measured over a 24-h period or body weights was not different. The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement. PMID:22362892

Srivastava, Shireesh; Kashiwaya, Yoshihiro; King, M Todd; Baxa, Ulrich; Tam, Joseph; Niu, Gang; Chen, Xiaoyuan; Clarke, Kieran; Veech, Richard L

2012-06-01

114

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. PMID:23056435

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

2012-01-01

115

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

PubMed

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. PMID:22419819

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

2012-05-01

116

Exercise-Induced Asthma  

Microsoft Academic Search

\\u000a \\u000a Key Points  \\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Exercise-induced asthma (EIA) occurs in 90% of individuals with asthma.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a The prevalence of EIA among athletes ranges between 3 and 11%.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a EIA is characterized by transient airway obstruction occurring after strenuous exertion.\\u000a \\u000a \\u000a \\u000a \\u000a • \\u000a \\u000a \\u000a Pathophysiological mechanisms that could possibly explain the phenomenon of EIA include respiratory, heat or water loss (or\\u000a both), hyperventilation leading to the

Rahmat Afrasiabi

117

Prohibitin overexpression in adipocytes induces mitochondrial biogenesis, leads to obesity development, and affects glucose homeostasis in a sex-specific manner.  

PubMed

Adipocytes are the primary cells in the body that store excess energy as triglycerides. To perform this specialized function, adipocytes rely on their mitochondria; however, the role of adipocyte mitochondria in the regulation of adipose tissue homeostasis and its impact on metabolic regulation is not understood. We developed a transgenic mouse model, Mito-Ob, overexpressing prohibitin (PHB) in adipocytes. Mito-Ob mice developed obesity due to upregulation of mitochondrial biogenesis in adipocytes. Of note, Mito-Ob female mice developed more visceral fat than male mice. However, female mice exhibited no change in glucose homeostasis and had normal insulin and high adiponectin levels, whereas male mice had impaired glucose homeostasis, compromised brown adipose tissue structure, and high insulin and low adiponectin levels. Mechanistically, we found that PHB overexpression enhances the cross talk between the mitochondria and the nucleus and facilitates mitochondrial biogenesis. The data suggest a critical role of PHB and adipocyte mitochondria in adipose tissue homeostasis and reveal sex differences in the effect of PHB-induced adipocyte mitochondrial remodeling on whole-body metabolism. Targeting adipocyte mitochondria may provide new therapeutic opportunities for the treatment of obesity, a major risk factor for type 2 diabetes. PMID:24947361

Ande, Sudharsana R; Nguyen, K Hoa; Padilla-Meier, G Pauline; Wahida, Wahida; Nyomba, B L Grégoire; Mishra, Suresh

2014-11-01

118

Overexpression of human selenoprotein H in neuronal cells enhances mitochondrial biogenesis and function through activation of protein kinase A, protein kinase B, and cyclic adenosine monophosphate response element-binding protein pathway.  

PubMed

Mitochondrial biogenesis is activated by nuclear encoded transcription co-activator peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?), which is regulated by several upstream factors including protein kinase A and Akt/protein kinase B. We have previously shown that selenoprotein H enhances the levels of nuclear regulators for mitochondrial biogenesis, increases mitochondrial mass and improves mitochondrial respiratory rate, under physiological condition. Furthermore, overexpression of selenoprotein H protects neuronal HT22 cells from ultraviolet B irradiation-induced cell damage by lowering reactive oxygen species production, and inhibiting activation of caspase-3 and -9, as well as p53. The objective of this study is to identify the cell signaling pathways by which selenoprotein H initiates mitochondrial biogenesis. We first confirmed our previous observation that selenoprotein H transfected HT22 cells increased the protein levels of nuclear-encoded mitochondrial biogenesis factors, peroxisome proliferator-activated receptor ? coactivator-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A. We then observed that total and phosphorylation of protein kinase A, Akt/protein kinase B and cyclic adenosine monophosphate response element-binding protein (CREB) were significantly increased in selenoprotein H transfected cells compared to vector transfected HT22 cells. To verify whether the observed stimulating effects on mitochondrial biogenesis pathways are caused by selenoprotein H and mediated through CREB, we knocked down selenoprotein H mRNA level using siRNA and inhibited CREB with napthol AS-E phosphate in selenoprotein H transfected cells and repeated the measurements of the aforementioned biomarkers. Our results revealed that silencing of selenoprotein H not only decreased the protein levels of PGC-1?, nuclear respiratory factor 1 and mitochondrial transcription factor A, but also decreased the total and phosphorylation levels of protein kinase A, protein kinase B, and CREB. Similarly, CREB inhibition reduced CREB activation and PGC-1? protein levels in selenoprotein H transfected cells. Moreover, selenoprotein H transfection increased the activity of mitochondrial complexes and prevented the ultraviolet B induced fall of mitochondrial membrane potential. We conclude that the effects of selenoprotein H on mitochondrial biogenesis and mitochondrial function are probably mediated through protein kinase A-CREB-PGC-1? and Akt/protein kinase B-CREB-PGC-1? pathways. PMID:23220172

Mehta, Suresh L; Mendelev, Natalia; Kumari, Santosh; Andy Li, P

2013-03-01

119

Two modular forms of the mitochondrial sorting and assembly machinery are involved in biogenesis of alpha-helical outer membrane proteins.  

PubMed

The mitochondrial outer membrane contains two translocase machineries for precursor proteins--the translocase of the outer membrane (TOM complex) and the sorting and assembly machinery (SAM complex). The TOM complex functions as the main mitochondrial entry gate for nuclear-encoded proteins, whereas the SAM complex was identified according to its function in the biogenesis of beta-barrel proteins of the outer membrane. The SAM complex is required for the assembly of precursors of the TOM complex, including not only the beta-barrel protein Tom40 but also a subset of alpha-helical subunits. While the interaction of beta-barrel proteins with the SAM complex has been studied in detail, little is known about the interaction between the SAM complex and alpha-helical precursor proteins. We report that the SAM is not static but that the SAM core complex can associate with different partner proteins to form two large SAM complexes with different functions in the biogenesis of alpha-helical Tom proteins. We found that a subcomplex of TOM, Tom5-Tom40, associates with the SAM core complex to form a new large SAM complex. This SAM-Tom5/Tom40 complex binds the alpha-helical precursor of Tom6 after the precursor has been inserted into the outer membrane in an Mim1 (mitochondrial import protein 1)-dependent manner. The second large SAM complex, SAM-Mdm10 (mitochondrial distribution and morphology protein), binds the alpha-helical precursor of Tom22 and promotes its membrane integration. We suggest that the modular composition of the SAM complex provides a flexible platform to integrate the sorting pathways of different precursor proteins and to promote their assembly into oligomeric complexes. PMID:20026336

Thornton, Nicolas; Stroud, David A; Milenkovic, Dusanka; Guiard, Bernard; Pfanner, Nikolaus; Becker, Thomas

2010-02-26

120

The Impact of Aging on Mitochondrial Function and Biogenesis Pathways in Skeletal Muscle of Sedentary High- and Low-Functioning Elderly Individuals  

PubMed Central

Summary Age-related loss of muscle mass and strength (sarcopenia) leads to a decline in physical function and frailty in the elderly. Among the many proposed underlying causes of sarcopenia, mitochondrial dysfunction is inherent in a variety of aged tissues. The intent of this study was to examine the effect of aging on key groups of regulatory proteins involved in mitochondrial biogenesis and how this relates to physical performance in two groups of sedentary elderly participants, classified as high- and low-functioning based on the Short Physical Performance Battery test. Muscle mass was decreased by 38% and 30% in low-functioning elderly (LFE) participants when compared to young and high-functioning elderly (HFE) participants, respectively, and positively correlated to physical performance. Mitochondrial respiration in permeabilized muscle fibers was reduced (41%) in the LFE group when compared to the young, and this was associated with a 30% decline in COX activity. Levels of key metabolic regulators, SIRT3 and PGC-1? were significantly reduced (50%) in both groups of elderly participants when compared to young. Similarly, the fusion protein OPA1 was lower in muscle from elderly subjects, however no changes were detected in Mfn2, Drp1 or Fis1 among the groups. In contrast, protein import machinery (PIM) components Tom22 and cHsp70 were increased in the LFE group when compared to the young. This study suggests that aging in skeletal muscle is associated with impaired mitochondrial function and altered biogenesis pathways, and that this may contribute to muscle atrophy and the decline in muscle performance observed in the elderly population. PMID:22681576

Joseph, Anna-Maria; Adhihetty, Peter J.; Buford, Thomas W.; Wohlgemuth, Stephanie E.; Lees, Hazel A.; Nguyen, Linda M.-D.; Aranda, Juan M.; Sandesara, Bhanu D.; Pahor, Marco; Manini, Todd M.; Marzetti, Emanuele; Leeuwenburgh, Christiaan

2012-01-01

121

Relative abundance of the human mitochondrial transcription system and distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression.  

PubMed

Human mitochondrial transcription requires the bacteriophage-related RNA polymerase, POLRMT, the mtDNA-binding protein, h-mtTFA/TFAM, and two transcription factors/rRNA methyltransferases, h-mtTFB1 and h-mtTFB2. Here, we determined the steady-state levels of these core transcription components and examined the consequences of purposeful elevation of h-mtTFB1 or h-mtTFB2 in HeLa cells. On a per molecule basis, we find an approximately 6-fold excess of POLRMT to mtDNA and approximately 3-fold more h-mtTFB2 than h-mtTFB1. We also estimate h-mtTFA at approximately 50 molecules/mtDNA, a ratio predicted to support robust transcription, but not to coat mtDNA. Consistent with a role for h-mtTFB2 in transcription and transcription-primed replication, increased mitochondrial DNA and transcripts result from its over-expression. This is accompanied by increased translation rates of most, but not all mtDNA-encoded proteins. Over-expression of h-mtTFB1 did not significantly influence these parameters, but did result in increased mitochondrial biogenesis. Furthermore, h-mtTFB1 mRNA and protein are elevated in response to h-mtTFB2 over-expression, suggesting the existence of a retrograde signal to the nucleus to coordinately regulate expression of these related factors. Altogether, our results provide a framework for understanding the regulation of human mitochondrial transcription in vivo and define distinct roles for h-mtTFB1 and h-mtTFB2 in mitochondrial biogenesis and gene expression that together likely fine-tune mitochondrial function. PMID:17557812

Cotney, Justin; Wang, Zhibo; Shadel, Gerald S

2007-01-01

122

Dietary Fucoxanthin Increases Metabolic Rate and Upregulated mRNA Expressions of the PGC-1alpha Network, Mitochondrial Biogenesis and Fusion Genes in White Adipose Tissues of Mice  

PubMed Central

The mechanism for how fucoxanthin (FX) suppressed adipose accumulation is unclear. We aim to investigate the effects of FX on metabolic rate and expressions of genes related to thermogenesis, mitochondria biogenesis and homeostasis. Using a 2 × 2 factorial design, four groups of mice were respectively fed a high sucrose (50% sucrose) or a high-fat diet (23% butter + 7% soybean oil) supplemented with or without 0.2% FX. FX significantly increased oxygen consumption and carbon dioxide production and reduced white adipose tissue (WAT) mass. The mRNA expressions of peroxisome proliferator-activated receptor (PPAR) ? coactivator-1? (PGC-1?), cell death-inducing DFFA-like effecter a (CIDEA), PPAR?, PPAR?, estrogen-related receptor ? (ERR?), ?3-adrenergic receptor (?3-AR) and deiodinase 2 (Dio2) were significantly upregulated in inguinal WAT (iWAT) and epididymal WAT (eWAT) by FX. Mitochondrial biogenic genes, nuclear respiratory factor 1 (NRF1) and NRF2, were increased in eWAT by FX. Noticeably, FX upregulated genes of mitochondrial fusion, mitofusin 1 (Mfn1), Mfn2 and optic atrophy 1 (OPA1), but not mitochondrial fission, Fission 1, in both iWAT and eWAT. In conclusion, dietary FX enhanced the metabolic rate and lowered adipose mass irrespective of the diet. These were associated with upregulated genes of the PGC-1? network and mitochondrial fusion in eWAT and iWAT. PMID:24534841

Wu, Meng-Ting; Chou, Hong-Nong; Huang, Ching-jang

2014-01-01

123

Exercise-induced asthma (image)  

MedlinePLUS

Exercise-induced asthma is distinct from allergic asthma in that it does not produce long-term increase in airway activity. People who only experience asthma when they exercise ... symptoms with preventive measures such as warm-up and cool-down ...

124

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

125

Exercise-induced Bronchospasm In Children  

Microsoft Academic Search

This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exerciseinduced\\u000a bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for\\u000a transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline\\u000a in pulmonary function by at least 10%. Exercise induced

Chris Randolph

2008-01-01

126

Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease  

PubMed Central

Increasing evidence suggests that the accumulation of amyloid beta (A?) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of A? in mitochondrial activity and synaptic alterations in neurons from a mouse model of AD. Using primary neurons from a well-characterized A? precursor protein transgenic (A?PP) mouse model (Tg2576 mouse line), for the first time, we studied mitochondrial activity, including axonal transport of mitochondria, mitochondrial dynamics, morphology and function. Further, we also studied the nature of A?-induced synaptic alterations, and cell death in primary neurons from Tg2576 mice, and we sought to determine whether the mitochondria-targeted antioxidant SS31 could mitigate the effects of oligomeric A?. We found significantly decreased anterograde mitochondrial movement, increased mitochondrial fission and decreased fusion, abnormal mitochondrial and synaptic proteins and defective mitochondrial function in primary neurons from A?PP mice compared with wild-type (WT) neurons. Transmission electron microscopy revealed a large number of small mitochondria and structurally damaged mitochondria, with broken cristae in A?PP primary neurons. We also found an increased accumulation of oligomeric A? and increased apoptotic neuronal death in the primary neurons from the A?PP mice relative to the WT neurons. Our results revealed an accumulation of intraneuronal oligomeric A?, leading to mitochondrial and synaptic deficiencies, and ultimately causing neurodegeneration in A?PP cultures. However, we found that the mitochondria-targeted antioxidant SS31 restored mitochondrial transport and synaptic viability, and decreased the percentage of defective mitochondria, indicating that SS31 protects mitochondria and synapses from A? toxicity. PMID:21873260

Calkins, Marcus J.; Manczak, Maria; Mao, Peizhong; Shirendeb, Ulziibat; Reddy, P. Hemachandra

2011-01-01

127

Impaired mitochondrial biogenesis, defective axonal transport of mitochondria, abnormal mitochondrial dynamics and synaptic degeneration in a mouse model of Alzheimer's disease.  

PubMed

Increasing evidence suggests that the accumulation of amyloid beta (A?) in synapses and synaptic mitochondria causes synaptic mitochondrial failure and synaptic degeneration in Alzheimer's disease (AD). The purpose of this study was to better understand the effects of A? in mitochondrial activity and synaptic alterations in neurons from a mouse model of AD. Using primary neurons from a well-characterized A? precursor protein transgenic (A?PP) mouse model (Tg2576 mouse line), for the first time, we studied mitochondrial activity, including axonal transport of mitochondria, mitochondrial dynamics, morphology and function. Further, we also studied the nature of A?-induced synaptic alterations, and cell death in primary neurons from Tg2576 mice, and we sought to determine whether the mitochondria-targeted antioxidant SS31 could mitigate the effects of oligomeric A?. We found significantly decreased anterograde mitochondrial movement, increased mitochondrial fission and decreased fusion, abnormal mitochondrial and synaptic proteins and defective mitochondrial function in primary neurons from A?PP mice compared with wild-type (WT) neurons. Transmission electron microscopy revealed a large number of small mitochondria and structurally damaged mitochondria, with broken cristae in A?PP primary neurons. We also found an increased accumulation of oligomeric A? and increased apoptotic neuronal death in the primary neurons from the A?PP mice relative to the WT neurons. Our results revealed an accumulation of intraneuronal oligomeric A?, leading to mitochondrial and synaptic deficiencies, and ultimately causing neurodegeneration in A?PP cultures. However, we found that the mitochondria-targeted antioxidant SS31 restored mitochondrial transport and synaptic viability, and decreased the percentage of defective mitochondria, indicating that SS31 protects mitochondria and synapses from A? toxicity. PMID:21873260

Calkins, Marcus J; Manczak, Maria; Mao, Peizhong; Shirendeb, Ulziibat; Reddy, P Hemachandra

2011-12-01

128

Biogenesis of Porin of the Outer Mitochondrial Membrane Involves an Import Pathway via Receptors and the General Import Pore of the Tom Complex  

PubMed Central

Porin, also termed the voltage-dependent anion channel, is the most abundant protein of the mitochondrial outer membrane. The process of import and assembly of the protein is known to be dependent on the surface receptor Tom20, but the requirement for other mitochondrial proteins remains controversial. We have used mitochondria from Neurospora crassa and Saccharomyces cerevisiae to analyze the import pathway of porin. Import of porin into isolated mitochondria in which the outer membrane has been opened is inhibited despite similar levels of Tom20 as in intact mitochondria. A matrix-destined precursor and the porin precursor compete for the same translocation sites in both normal mitochondria and mitochondria whose surface receptors have been removed, suggesting that both precursors utilize the general import pore. Using an assay established to monitor the assembly of in vitro–imported porin into preexisting porin complexes we have shown that besides Tom20, the biogenesis of porin depends on the central receptor Tom22, as well as Tom5 and Tom7 of the general import pore complex (translocase of the outer mitochondrial membrane [TOM] core complex). The characterization of two new mutant alleles of the essential pore protein Tom40 demonstrates that the import of porin also requires a functional Tom40. Moreover, the porin precursor can be cross-linked to Tom20, Tom22, and Tom40 on its import pathway. We conclude that import of porin does not proceed through the action of Tom20 alone, but requires an intact outer membrane and involves at least four more subunits of the TOM machinery, including the general import pore. PMID:11266446

Krimmer, Thomas; Rapaport, Doron; Ryan, Michael T.; Meisinger, Chris; Kassenbrock, C. Kenneth; Blachly-Dyson, Elizabeth; Forte, Michael; Douglas, Michael G.; Neupert, Walter; Nargang, Frank E.; Pfanner, Nikolaus

2001-01-01

129

Biogenesis of porin of the outer mitochondrial membrane involves an import pathway via receptors and the general import pore of the TOM complex.  

PubMed

Porin, also termed the voltage-dependent anion channel, is the most abundant protein of the mitochondrial outer membrane. The process of import and assembly of the protein is known to be dependent on the surface receptor Tom20, but the requirement for other mitochondrial proteins remains controversial. We have used mitochondria from Neurospora crassa and Saccharomyces cerevisiae to analyze the import pathway of porin. Import of porin into isolated mitochondria in which the outer membrane has been opened is inhibited despite similar levels of Tom20 as in intact mitochondria. A matrix-destined precursor and the porin precursor compete for the same translocation sites in both normal mitochondria and mitochondria whose surface receptors have been removed, suggesting that both precursors utilize the general import pore. Using an assay established to monitor the assembly of in vitro-imported porin into preexisting porin complexes we have shown that besides Tom20, the biogenesis of porin depends on the central receptor Tom22, as well as Tom5 and Tom7 of the general import pore complex (translocase of the outer mitochondrial membrane [TOM] core complex). The characterization of two new mutant alleles of the essential pore protein Tom40 demonstrates that the import of porin also requires a functional Tom40. Moreover, the porin precursor can be cross-linked to Tom20, Tom22, and Tom40 on its import pathway. We conclude that import of porin does not proceed through the action of Tom20 alone, but requires an intact outer membrane and involves at least four more subunits of the TOM machinery, including the general import pore. PMID:11266446

Krimmer, T; Rapaport, D; Ryan, M T; Meisinger, C; Kassenbrock, C K; Blachly-Dyson, E; Forte, M; Douglas, M G; Neupert, W; Nargang, F E; Pfanner, N

2001-01-22

130

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. PMID:8869196

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

1996-01-01

131

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

132

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

2012-02-01

133

The role of heme and iron-sulfur clusters in mitochondrial biogenesis, maintenance, and decay with age.  

PubMed

Mitochondria decay with age from oxidative damage and loss of protective mechanisms. Resistance, repair, and replacement mechanisms are essential for mitochondrial preservation and maintenance. Iron plays an essential role in the maintenance of mitochondria, through its two major functional forms: heme and iron-sulfur clusters. Both iron-based cofactors are formed and utilized in the mitochondria and then distributed throughout the cell. This is an important function of mitochondria that is not directly related to the production of ATP. Heme and iron-sulfur clusters are important for the normal assembly and for the optimal activity of the electron transfer complexes. Loss of mitochondrial cytochrome c oxidase (complex IV), integrity of mtDNA, and function can result from abnormal homeostasis of iron. We review the physiological role of iron-sulfur clusters and heme in the integrity of the mitochondria and the generation of oxidants. PMID:11795893

Atamna, Hani; Walter, Patrick B; Ames, Bruce N

2002-01-15

134

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

Microsoft Academic Search

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

Yann Saint-Georges; Mathilde Garcia; Thierry Delaveau; Laurent Jourdren; Stephane Le Crom; Sophie Lemoine; Veronique Tanty; Frederic Devaux; Claude Jacq; Jürg Bähler

2008-01-01

135

Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus.  

PubMed

We measured plasma levels of the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and leucocyte mRNA expression levels of the genes encoding the 8-OHdG repair enzyme human 8-oxoguanine DNA glycosylase 1 (hOGG1), the anti-oxidant enzymes copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase-1 (GPx-1), GPx-4, glutathione reductase (GR) and glutathione synthetase (GS), the mitochondrial biogenesis-related proteins mtDNA-encoded ND 1 polypeptide (ND1), ND6, ATPase 6, mitochondrial transcription factor A (Tfam), nuclear respiratory factor 1(NRF-1), pyruvate dehydrogenase E1 component alpha subunit (PDHA1), pyruvate dehydrogenase kinase isoenzyme 1 (PDK-1) and hypoxia inducible factor-1? (HIF-1?) and the glycolytic enzymes hexokinase-II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase A (LDHa). We analysed their relevance to oxidative damage in 85 systemic lupus erythematosus (SLE) patients, four complicated SLE patients undergoing rituximab treatment and 45 healthy individuals. SLE patients had higher plasma 8-OHdG levels (P?mitochondrial biogenesis-related proteins (P?mitochondrial biogenesis-related proteins (P?mitochondrial biogenesis and glucose metabolism may be implicated in SLE deterioration, and this impairment might be improved by targeted biological therapy. PMID:24345202

Lee, H-T; Lin, C-S; Lee, C-S; Tsai, C-Y; Wei, Y-H

2014-04-01

136

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

PubMed Central

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, Hakan

2010-01-01

137

Crosstalk between mitochondrial (dys)function and mitochondrial abundance.  

PubMed

A controlled regulation of mitochondrial mass through either the production (biogenesis) or the degradation (mitochondrial quality control) of the organelle represents a crucial step for proper mitochondrial and cell function. Key steps of mitochondrial biogenesis and quality control are overviewed, with an emphasis on the role of mitochondrial chaperones and proteases that keep mitochondria fully functional, provided the mitochondrial activity impairment is not excessive. In this case, the whole organelle is degraded by mitochondrial autophagy or "mitophagy." Beside the maintenance of adequate mitochondrial abundance and functions for cell homeostasis, mitochondrial biogenesis might be enhanced, through discussed signaling pathways, in response to various physiological stimuli, like contractile activity, exposure to low temperatures, caloric restriction, and stem cells differentiation. In addition, mitochondrial dysfunction might also initiate a retrograde response, enabling cell adaptation through increased mitochondrial biogenesis. PMID:21928343

Michel, Sébastien; Wanet, Anaïs; De Pauw, Aurélia; Rommelaere, Guillaume; Arnould, Thierry; Renard, Patricia

2012-06-01

138

Exercise induced asthma and endogenous opioids  

Microsoft Academic Search

Concentrations of endogenous opioid peptides in the plasma are increased during exercise and these substances have been implicated in the pathogenesis of asthma induced by chloropropramide and alcohol in diabetic patients. This work was undertaken to determine whether exercise induced asthma might be mediated by endogenous opioids. Plasma beta endorphin, met-enkephalin, and adrenocorticotrophic hormone (ACTH) concentrations were measured in five

R C Gaillard; M Bachman; T Rochat; D Egger; R de Haller; A F Junod

1986-01-01

139

Exercise-induced asthma and doxantrazole  

Microsoft Academic Search

In a double-blind cross-over trial in 13 patients with exercise-induced asthma, doxantrazole 200 mg taken orally 1 hour before a standardized exercise test involving stair climbing failed to block post-exercise bronchoconstriction. In an open assessment study with the same patients, increasing the doxantrazole dose to 400 mg did not affect post-exercise bronchoconstriction.

H. Poppius; B. Stenius

1977-01-01

140

Nedocromil sodium and exercise induced asthma  

Microsoft Academic Search

Serial exercise tests were carried out by 12 children with asthma on two study days. After a control exercise test either nedocromil sodium 4 mg or placebo were given double blind by metered dose inhaler. Highly significant inhibition of exercise induced asthma occurred after nedocromil, lasting for over two hours.

N Chudry; F Correa; M Silverman

1987-01-01

141

Effect of cetirizine on exercise induced asthma  

Microsoft Academic Search

The effect of oral and inhaled cetirizine, a potent and specific H1 receptor antagonist, was studied in patients with exercise induced asthma. Twelve patients (five male; mean age 35.2 years) were given oral placebo or cetirizine 10 mg twice daily for one week, double blind and in randomised order, and exercised on a treadmill for six to eight minutes at

S K Ghosh; C De Vos; I McIlroy; K R Patel

1991-01-01

142

Calcium antagonists in exercise-induced asthma  

Microsoft Academic Search

Ten patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled verapamil (estimated dose 3 mg) and sodium cromoglycate (estimated dose 12 mg). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after running on a treadmill for eight minutes. There was

K R Patel

1981-01-01

143

Mechanisms of exercise-induced asthma  

Microsoft Academic Search

In a previous review in this journal McFadden eloquently presented the findings which led him and his colleagues to propose\\u000a that respiratory heat loss and the subsequent cooling of the airways are the initial reaction sequence leading to airway obstruction\\u000a in hyperventilation and exercise-induced asthma [62]. He further concluded that: “Exercise per se is not essential and serves\\u000a only as

Ephraim Bar-Yishay; Simon Godfrey

1984-01-01

144

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 Central

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

2013-01-01

145

The conserved mitochondrial twin Cx9C protein Cmc2 Is a Cmc1 homologue essential for cytochrome c oxidase biogenesis  

Microsoft Academic Search

Mitochondrial copper metabolism and delivery to cytochrome c oxidase and mitochondrially localized CuZn-superoxide dismutase (Sod1) requires a growing number of intermembrane space proteins containing a twin Cx(9)C motif. Among them, Cmc1 was recently identified by our group. Here we describe another conserved mitochondrial metallochaperone-like protein, Cmc2, a close homologue of Cmc1, whose function affects both cytochrome c oxidase and Sod1.

D. Horn; W. Zhou; E. Trevisson; H. Al-Ali; T. K. Harris; L. Salviati; A. Barrientos

2010-01-01

146

Activation of the Iron Regulon by the Yeast Aft1\\/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis  

Microsoft Academic Search

Two transcriptional activators, Aft1 and Aft2, regulate iron homeostasis in Saccharomyces cerevisiae. These factors induce the expression of iron regulon genes in iron-deficient yeast but are inactivated in iron-replete cells. Iron inhibition of Aft1\\/Aft2 is abrogated in cells defective for Fe-S cluster biogenesis within the mito- chondrial matrix (Chen, O. S., Crisp, R. J., Valachovic, M., Bard, M., Winge, D.

Julian C. Rutherford; Luis Ojeda; Janneke Balk; Ulrich Muhlenhoff; Roland Lill; Dennis R. Winge

2005-01-01

147

Exercise-Induced Bronchoconstriction and Exercise-Induced Respiratory Symptoms in Nurses  

PubMed Central

In order to assess prevalence and characteristics of exercise-induced respiratory symptoms (EIRSs) and exercise-induced bronchoconstriction (EIB) in health care workers, we performed a cross-sectional study including 48 female nurses from primary care settings and an equal number of female office workers studied as a control group. The evaluation of examined groups included completion of a questionnaire, skin prick tests to common inhalant allergens, spirometry, and exercise and histamine challenge. We found a similar prevalence of EIRSs and EIB in both groups. EIB was closely related to asthma, atopy, family history of asthma, and positive histamine challenge in either group, while the association between EIB and daily smoking in nurses was of borderline statistical significance. Bronchial reaction to exercise was significantly higher in nurses than in controls with EIB. With the exception of exercise induced wheezing, EIRSs were weakly associated with EIB in both groups with a large proportion of false positive results. PMID:21747865

Minov, Jordan; Karadzinska-Bislimovska, Jovanka; Vasilevska, Kristin; Risteska-Kuc, Snezana; Stoleski, Saso; Mijakoski, Dragan

2011-01-01

148

How to diagnose exercise induced asthma?  

PubMed

Exercise induced asthma (EIA) is a transient increase in airway resistance after intensive exercise and can be measured as a decline in forced expiratory volume in one second (FEV1). The condition is due to increased training load and inhalation of cold and dry air. Several studies have shown that eucapnic voluntary hyperpnea challenge test (EVH test) is a very sensitive and specific diagnostic method. EVH test develops EIA by hyperventilation of dry gas and the test achieves the same airway obstruction as training in cold and dry air. The test is better than the previously used methacholine challenge test. PMID:22375220

Ali, Zarqa

2011-06-01

149

Keeping Children With Exercise-induced Asthma Active  

Microsoft Academic Search

Exercise-induced bronchospasm, exercise- induced bronchoconstriction, and exercise-induced asthma (EIA) are all terms used to describe the phenom- enon of transient airflow obstruction associated with physical exertion. It is a prominent finding in children and young adults because of their greater participation in vigorous activities.1 The symptoms—shortness of breath, cough, chest tightness, and wheezing—normally follow the brief period of bronchodilation present

Henry Milgrom; Lynn M. Taussig

2010-01-01

150

Exercise-induced airways constriction 1  

PubMed Central

Airway conductance was measured in a body plethysmograph at different lung volumes before and after graded exercise. In 14 out of 19 patients, mostly asthmatics, airway conductance fell significantly after exercise. These subjects also showed other signs of an increased bronchial reactivity to different stimuli, including forced breathing, hyperventilation, and cold air, but they had no exogenous allergy. The exercise-induced bronchoconstriction could be blocked by atropine in six of the nine patients tested. Exercise-induced bronchoconstriction in patients with clinical and physiological evidence of increased airway reactivity thus seems to be primarily mediated via a vagal reflex, probably from hyperresponsive airway mechanoreceptors reacting to increased ventilatory flow or lung distension. No relation was found between PaCO2 or pH and the severity of airways constriction. Cromoglycic acid failed to block the exercise reaction in five of the six hyperreactive patients tested. In addition to or following the vagal reflex a disturbed relation between beta and alpha receptors in bronchial muscles or a release of humoral spasmogens may contribute to the progression of post-exercise airways constriction. PMID:4624586

Simonsson, Bo G.; Skoogh, B-E.; Ekstrom-Jodal, B.

1972-01-01

151

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

152

Detecting exercise induced stress using the photoplethysmogram.  

PubMed

The effect of exercise on the cardiovascular system has been studied extensively using a wide range of physiological sensors. Athletes now commonly use EKG-based monitors to ascertain heart rate, but these devices cannot directly monitor the level of physical stress. We hypothesize that the low frequency spindle waves seen in the photoplethysmographs (PPG) of exercising individuals may be useful for noninvasively detecting hemodynamic stressors to the human vascular system. In a clinical trial with nine healthy subjects performing the Bruce Protocol treadmill test these low frequency spindle waves were observed in the forehead and ear PPG in all subjects before the onset of volitional fatigue. As volitional fatigue approached, the spindle waves become more pronounced, decreased in period and then within several seconds of the cessation of the protocol they disappeared. Using a software-based detector, these distinct spindle waves can be reliably detected. This technique holds promise for the automatic detection and characterization of exercise induced physical stress. PMID:17945875

Linder, Stephen Paul; Wendelken, Suzanne; Clayman, Jeffrey

2006-01-01

153

Exercise induces metallothioneins in mouse spinal cord.  

PubMed

Regular exercise has displayed a beneficial effect on the progression of amyotrophic lateral sclerosis (ALS). However, the mechanism is poorly understood. We here present that regular exercise on a treadmill induces metallothioneins (MTs: MT-1, MT-2, and MT-3) in spinal cords of mice. As MTs are strong scavengers of reactive oxygen species and have some neurotrophic activities, exercise may have some beneficial effects on spinal motor neurons in patients with ALS owing to the induction of MTs. The running exercise on a treadmill for 30 min/day increased the mRNA expression levels of MT-1, MT-2, and MT-3 up to 193%, 298%, and 196%, respectively, of the control value 12 h after the start of exercise. After two weeks of daily exercise, Western blotting of the MTs proteins showed that the expression levels of MT-1/2 and MT-3 reached 173% and 146%, respectively, compared with those in sedentary mice. Running exercise on a treadmill for 2 weeks led to the gradual accumulation of MT proteins in the spinal cords of the mice. In addition, MT-1/2 and MT-3 immunoreactivities were enhanced in astrocytes particularly in the gray matter of the spinal cord. We revealed that regular exercise induced transient increases in the expression levels of MT mRNAs and resulted in accumulation of MT proteins in the spinal cords of the normal mice. PMID:19490933

Hashimoto, K; Hayashi, Y; Inuzuka, T; Hozumi, I

2009-09-29

154

Wheezing or Breezing through Exercise-Induced Asthma.  

ERIC Educational Resources Information Center

Several physicians discuss the tests they use to diagnose exercise-induced asthma (EIA), the medications they typically prescribe and why, and the importance of properly educating athletes about EIA. (JD)

McCarthy, Paul

1989-01-01

155

Exercise-induced respiratory symptoms not due to asthma.  

PubMed

This manuscript describes two interesting patients who had exercise-induced symptoms that unmasked an alternative underlying diagnosis. The first is an 8-year-old boy who was treated for asthma all his life but really had exercise-induced stridor (labelled as wheeze) causing significant exercise limitation, which was due to a double aortic arch with the right arch compressing the trachea. The second case describes the diagnosis of vocal cord dysfunction in a 13-year-old anxious high achiever. He also initially had exercise-induced symptoms treated as exercise-induced wheeze but again had a stridor due to vocal cord dysfunction. Both these cases demonstrate the importance of detailed history including during exercise, which can unmask alternative diagnosis. Another important message is that if there is no response to bronchodilator treatment with absence of typical signs and symptoms of asthma, alternative diagnosis should be considered. PMID:22050200

Pandit, Chetan A; Batterby, Eugenie; Van Asperen, Peter; Cooper, Peter; Selvadurai, Hiran; Fitzgerald, Dominic A

2014-10-01

156

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

157

Exercise-induced asthma and cardiovascular fitness in asthmatic children  

Microsoft Academic Search

BACKGROUND: The role of physical training in the management of children with exercise-induced asthma is controversial. A study was undertaken to determine whether a relationship could be found between the occurrence of exercise-induced asthma and the degree of cardiovascular fitness in asthmatic children. METHODS: Twenty eight children aged 6-13 with mild to moderate asthma and dyspnoea during or after physical

B. J. Thio; A. F. Nagelkerke; A. G. Ketel; B. L. van Keeken; J. E. Dankert-Roelse

1996-01-01

158

Exercise-Induced Anaphylaxis: An Update on Diagnosis and Treatment  

Microsoft Academic Search

Exercise-induced anaphylaxis (EIA) and food-dependent, exercise-induced anaphylaxis (FDEIA) are rare but potentially life-threatening\\u000a clinical syndromes in which association with exercise is crucial. The range of triggering physical activities is broad, including\\u000a as mild an effort as a stroll. EIA is not fully repeatable (ie, the same exercise may not always result in anaphylaxis in\\u000a a given patient). In FDEIA, the

Wojciech Barg; Wojciech Medrala; Anna Wolanczyk-Medrala

2011-01-01

159

Mechanisms and Management of Exercise-Induced Bronchoconstriction  

Microsoft Academic Search

The term “exercise-induced asthma” has been used to describe the transient narrowing of the airways and the subsequent increase\\u000a in airway resistance, which can occur during, though more commonly following, vigorous exercise [1]. Exercise is a trigger\\u000a for bronchoconstriction in individuals with asthma, but is not considered an independent risk factor for the development of\\u000a asthma. The term “exercise-induced asthma”

John D. Brannan; Paul M. O'Byrne

160

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. PMID:22767599

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

2012-01-01

161

Resveratrol Attenuates Exercise-Induced Adaptive Responses in Rats Selectively Bred for Low Running Performance  

PubMed Central

Low capacity runner (LCR) rats have been developed by divergent artificial selection for treadmill endurance capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running. In this study it was examined whether 12 weeks of treadmill exercise training and/or resveratrol can retrieve the low running performance of the LCR and impact mitochondrial biogenesis and quality control. Resveratrol regressed running performance in trained LCR (p<0.05). Surprisingly, exercise and resveratrol treatments significantly decreased pAMPK/AMPK, SIRT1, SIRT4, forkhead transcription factor 1 (FOXO1) and mitochondrial transcription factor A (TFAM) levels in these animals (p<0.05). Mitochondrial fusion protein, HSP78 and polynucleotide phosphorylase were significantly induced in LCR-trained, LCR-resveratrol treated, LCR-trained and resveratol treated groups compared to LCR-controls. The data indicate that the AMPK-SIRT1-NAMPT-FOXO1 axis could be important to the limited aerobic endurance capacity of low running capacity rats. Resveratrol supplementation was not beneficial in terms of aerobic endurance performance, mitochondrial biogenesis, or quality control. PMID:24659933

Hart, Nikolett; Sarga, Linda; Csende, Zsolt; Koch, Lauren G.; Britton, Steven L.; Davies, Kelvin J.A.; Radak, Zsolt

2014-01-01

162

Exercise-induced bronchoconstriction in Tunisian elite athletes is underdiagnosed  

PubMed Central

Many studies have shown an increased risk of developing exercise-induced bronchoconstriction among the athletic population, particularly at the elite level. Subjective methods for assessing exercise-induced bronchoconstriction such as surveys and questionnaires have been used but have resulted in an underestimation of the prevalence of airway dysfunction when compared with objective measurements. The aim of the present study was to compare the prevalence of exercise-induced bronchoconstriction among Tunisian elite athletes obtained using an objective method with that using a subjective method, and to discuss the possible causes and implications of the observed discrepancy. As the objective method we used spirometry before and after exercise and for the subjective approach we used a medical history questionnaire. All of the recruited 107 elite athletes responded to the questionnaire about respiratory symptoms and medical history and underwent a resting spirometry testing before and after exercise. Post-exercise spirometry revealed the presence of exercise-induced bronchoconstriction in 14 (13%) of the elite athletes, while only 1.8% reported having previously been diagnosed with asthma. In conclusion, our findings indicate that medical history-based diagnoses of exercise-induced bronchoconstriction lead to underestimations of true sufferers. PMID:24198569

Sallaoui, Ridha; Zendah?, Ines; Ghedira?, Habib; Belhaouz?, Mohcine; Ghrairi?, Mourad; Amri?, Mohamed

2011-01-01

163

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

164

Regulation of mitochondrial biogenesis. Occurrence of non-functioning components of the mitochondrial respiratory chain in Saccharomyces cerevisiae grown in the presence of proteinase inhibitors: evidence for proteolytic control over assembly of the respiratory chain.  

PubMed Central

Yeast was grown in glucose- or galactose-containing media without or with proteinase inhibitors, phenylmethanesulphonyl fluoride and pepstatin. Culture growth was practically not affected by these compounds. Yeast growth on glucose in the presence of either phenylmethanesulphonyl fluoride or pepstatin entails accumulation of cytochromes c, c1, b and aa3 to a 25--30% excess above the control by the stationary phase, while cell respiration is unaffected. During growth on galactose the maximal cytochrome content (per unit weight of biomass) is reached in the mid-exponential phase and then decreases by 30--40% towards the stationary phase, while cell respiration remains constant. Addition of phenylmethanesulphonyl fluoride or pepstatin in the mid-exponential phase blocks the decrease in cytochrome levels and has no effect on cell respiration. Mitochondrial populations isolated from stationary-phase control and phenylmethanesulphonyl fluoride-grown cells glucose cultures display identical succinate oxidase and partial-respiratory-chain activities, despite the differences in cytochrome contents. However, the activities of individual respiratory complexes measured after maximal activation are nearly proportional to the amounts of corresponding components. The same situation holds true for mitochondrial populations from mid-exponential-phase, stationary-phase control and stationary-phase inhibitor-grown cells of galactose cultures. The findings suggest that the 'surplus' respiratory-chain components do not participate in electron flow because of the lack of interaction with adjacent carriers. PMID:7004440

Galkin, A V; Tsoi, T V; Luzikov, V N

1980-01-01

165

Postexercise whole body heat stress additively enhances endurance training-induced mitochondrial adaptations in mouse skeletal muscle.  

PubMed

A recent study demonstrated that heat stress induces mitochondrial biogenesis in C2C12 myotubes, thereby implying that heat stress may be an effective treatment to enhance endurance training-induced mitochondrial adaptations in skeletal muscle. However, whether heat stress actually induces mitochondrial adaptations in skeletal muscle in vivo is unclear. In the present study, we report the novel findings that 1) whole body heat stress produced by exposure of ICR mice to a hot environment (40°C, 30 min/day, 5 days/wk, 3 wk) induced mitochondrial adaptations such as increased mitochondrial enzyme activity (citrate synthase and 3-hydroxyacyl CoA dehydrogenase) and respiratory chain protein content (complexes I-V) in skeletal muscle in vivo and 2) postexercise whole body heat stress additively enhanced endurance training-induced mitochondrial adaptations (treadmill running, 25 m/min, 30 min/day, 5 days/wk, 3 wk). Moreover, to determine the candidate mechanisms underlying mitochondrial adaptations, we investigated the acute effects of postexercise whole body heat stress on the phosphorylation status of cellular signaling cascades that subsequently induce mitochondrial gene transcription. We found that whole body heat stress boosted the endurance exercise-induced phosphorylation of p38 MAPK, increased the phosphorylation status of p70S6K, a biomarker of mammalian target of rapamycin complex 1 activity, and unexpectedly dephosphorylated AMP-activated protein kinase and its downstream target acetyl-CoA carboxylase in skeletal muscle. Our present observations suggest that heat stress can act as an effective postexercise treatment. Heat stress treatment appeared to be clinically beneficial for people who have difficulty participating in sufficient exercise training, such as the elderly, injured athletes, and patients. PMID:25080501

Tamura, Yuki; Matsunaga, Yutaka; Masuda, Hiroyuki; Takahashi, Yumiko; Takahashi, Yuki; Terada, Shin; Hoshino, Daisuke; Hatta, Hideo

2014-10-01

166

Genetic interactions in the control of mitochondrial function in Paramecium  

Microsoft Academic Search

In an attempt to understand the genetic interactions between nuclear and mitochondrial genomes leading to mitochondrial biogenesis, different combinations of known nuclear and mitochondrial mutations have been constructed by microinjection. Eleven different tetrazolium resistant mutant strains, many clearly affecting mitochondrial function, were mjected with mitochondria from four different erythromycin resistant mitochondrial mutants. Cases were found in which mutant mitochondria were

Françoise Ruiz; Jonathan Knowles

1980-01-01

167

Detecting Exercise Induced Stress using the Photoplethysmogram Stephen Paul Linder*  

E-print Network

1 Detecting Exercise Induced Stress using the Photoplethysmogram Stephen Paul Linder* spl. of Cardiology *Dartmouth College, **Dartmouth Hitchcock Medical Center Hanover, NH, USA Abstract The effect sensors. Athletes now commonly use EKG-based monitors to ascertain heart rate, but these devices cannot

Linder, Stephen

168

Coping with Exercise-Induced Asthma in Sports.  

ERIC Educational Resources Information Center

This article reviews the history of research on exercise-induced asthma (EIA) and the pathophysiology of the condition, including its development and influencing factors. Four groups of drugs that are effective against EIA--theopyhlline, beta-adrenergic agents, cromolyn sodium, and anticholinergics--are discussed. (Author/CB)

Katz, Roger M.

1987-01-01

169

Cholinergic blockade in the prevention of exercise-induced asthma  

Microsoft Academic Search

The contribution of vagal mechanisms to exercise-induced asthma has been studied in 10 adult asthmatic patients using the anticholinergic drug ipratropium bromide. Exercise tests were performed for eight minutes on a cycle ergometer and each individual's tests were standardised by matching oxygen uptake. Two tests were done on each of three study days, the first being without previous medication, and

J P Hartley; B H Davies

1980-01-01

170

Effect of Disodium Cromoglycate on Exercise-induced Asthma  

Microsoft Academic Search

In eight patients with exercise-induced asthma, disodium cromoglycate was found to produce a definite inhibition of the post-exercise fall in forced expiratory volume in one second. This effect may be part of the cause for the subjective improvement experienced with this drug.

S. E. Davies

1968-01-01

171

The mechanism of exercise-induced asthma is …  

Microsoft Academic Search

Exercise-induced asthma (EIA) refers to the transient narrowing of the airways that follows vigorous exercise. The mechanism whereby EIA occurs is thought to relate to the consequences of heating and humidifying large volumes of air during exercise. In 1978 airway cooling was identified as an important stimulus for EIA; however, severe EIA also occurred when hot dry air was inspired,

Sandra D. Anderson; Evangelia Daviskas

2000-01-01

172

Ketotifen in atopic asthma and exercise-induced asthma  

Microsoft Academic Search

The efficacy of ketotifen, a tricyclic benzocycloheptathiophene derivative, was assessed in an outpatient clinical trial and in a group of 12 asthmatic subjects with exercise-induced asthma. Subjects in the outpatient trial had mild asthma and consisted of two groups: a group of 24 atopic asthmatics with at least one positive skin test reaction and with an associated history of bronchial

I S Petheram; J Moxham; C W Bierman; M McAllen; S G Spiro

1981-01-01

173

Diagnosis and Management of Exercise-Induced Asthma.  

ERIC Educational Resources Information Center

Exercise-induced asthma (EIA) affects 12-15% of the population. This comprehensive guide suggests that nearly all individuals with EIA can be active, highlighting both pharmacologic and nonpharmacologic management of asthma and stressing the importance of rigorous patient education in controlling underlying asthma and EIA. (SM)

Rupp, Ned T.

1996-01-01

174

Histamine reactivity during the refractory period after exercise induced asthma  

Microsoft Academic Search

An episode of exercise induced asthma will usually be followed by a period during which further exercise will not induce asthma. Postulated mechanisms include persistence of catecholamines released during exercise, development of tolerance to released mediators, and mediator depletion. To investigate the underlying mechanism further eight asthmatic men underwent three experimental protocols as follows: two treadmill runs of eight minutes;

A G Hahn; S G Nogrady; D M Tumilty; S R Lawrence; A R Morton

1984-01-01

175

Prevention of exercise induced asthma by inhaled salmeterol xinafoate  

Microsoft Academic Search

The effect of inhaled salmeterol xinafoate, a long acting beta 2 agonist, on exercise induced asthma was studied in a double blind, crossover, and placebo controlled trial. Thirteen asthmatic children with a fall of at least 15% in their forced expiratory volume in one second (FEV1) after a standard exercise test on a motorised treadmill, on separate days performed the

C P Green; J F Price

1992-01-01

176

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...

177

CARDIOMYOPATHY Exercise-Induced Left Ventricular Systolic Dysfunction  

E-print Network

CARDIOMYOPATHY Exercise-Induced Left Ventricular Systolic Dysfunction in Women Heterozygous: Cardiomyopathy, Women, Exercise, Heart failure, Echocardiography In men, mutations in the X-linked gene encoding. Acquired abnormality of the cellular localization of dystrophin is a component of cardiomyopathy due

Campbell, Kevin P.

178

Sodium cromoglycate and ipratropium bromide in exercise-induced asthma  

Microsoft Academic Search

In thirteen patients with extrinsic asthma the effects of placebo, sodium cromoglycate, ipratropium bromide, and ipratropium bromide plus sodium cromoglycate were studied in a random double-blind fashion to assess their inhibitory action in exercise-induced asthma (EIA). Exercise testing consisted of steady state running on an inclined treadmill for up to eight minutes. In eight of the 13 patients studied the

N C Thomson; K R Patel; J W Kerr

1978-01-01

179

Exercise-induced bronchoconstriction and atopy in Tunisian athletes  

Microsoft Academic Search

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%

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

2009-01-01

180

Effect of GR32191, a potent thromboxane receptor antagonist, on exercise induced bronchoconstriction in asthma  

Microsoft Academic Search

Previous work suggests a role for mast cell derived mediators in exercise induced asthma. The contribution of newly generated contractile prostaglandins to exercise induced asthma was assessed by using a potent and orally active thromboxane (TP1) receptor antagonist, GR32191. The effect of 120 mg GR32191 on exercise induced asthma was observed in 12 asthmatic subjects. For the exercise challenge the

J P Finnerty; O P Twentyman; A Harris; J B Palmer; S T Holgate

1991-01-01

181

Mitochondrial remodeling in hepatic differentiation and dedifferentiation.  

PubMed

Mitochondrial biogenesis and metabolism have recently emerged as important actors of stemness and differentiation. On the one hand, the differentiation of stem cells is associated with an induction of mitochondrial biogenesis and a shift from glycolysis toward oxidative phosphorylations (OXPHOS). In addition, interfering with mitochondrial biogenesis or function impacts stem cell differentiation. On the other hand, some inverse changes in mitochondrial abundance and function are observed during the reprogramming of somatic cells into induced pluripotent stem cells (iPSCs). Yet although great promises in cell therapy might generate better knowledge of the mechanisms regulating the stemness and differentiation of somatic stem cells (SSCs)-which are preferred over embryonic stem cells (ESCs) and iPSCs because of ethical and safety considerations-little interest was given to the study of their mitochondria. This study provides a detailed characterization of the mitochondrial biogenesis occurring during the hepatogenic differentiation of bone marrow-mesenchymal stem cells (BM-MSCs). During the hepatogenic differentiation of BM-MSCs, an increased abundance of mitochondrial DNA (mtDNA) is observed, as well as an increased expression of several mitochondrial proteins and biogenesis regulators, concomitant with increased OXPHOS activity, capacity, and efficiency. In addition, opposite changes in mitochondrial morphology and in the abundance of several OXPHOS subunits were found during the spontaneous dedifferentiation of primary hepatocytes. These data support reverse mitochondrial changes in a different context from genetically-engineered reprogramming. They argue in favor of a mitochondrial involvement in hepatic differentiation and dedifferentiation. PMID:25084555

Wanet, Anaïs; Remacle, Noémie; Najar, Mehdi; Sokal, Etienne; Arnould, Thierry; Najimi, Mustapha; Renard, Patricia

2014-09-01

182

AICAR inhibits cancer cell growth and triggers cell-type distinct effects on OXPHOS biogenesis, oxidative stress and Akt activation  

Microsoft Academic Search

The AMP-activated protein kinase agonist AICAR mimics a low intracellular energy state and inhibits the proliferation of cancer cells by different mechanisms, which may depend on the bioenergetic signature of these cells. AICAR can also stimulate mitochondrial biogenesis in myoblasts, neurons and HeLa cells. Yet, whether the reactivation of oxidative phosphorylation biogenesis by AICAR contributes to the growth arrest of

Caroline Jose; Etienne Hébert-Chatelain; Nadège Bellance; Anaïs Larendra; Melser Su; Karine Nouette-Gaulain; Rodrigue Rossignol

2011-01-01

183

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

184

Exercise-induced phospho-proteins in skeletal muscle  

Microsoft Academic Search

Efforts to identify exercise-induced signaling events in skeletal muscle have been influenced by ground-breaking discoveries in the insulin action field. Initial discoveries demonstrating that exercise enhances insulin sensitivity raised the possibility that contraction directly modulates insulin receptor signaling events. Although the acute effects of exercise on glucose metabolism are clearly insulin-independent, the canonical insulin signaling cascade has been used as

A S Deshmukh; J A Hawley; J R Zierath; JR Zierath

2008-01-01

185

Effect of acupuncture on exercise-induced asthma  

Microsoft Academic Search

Sixteen young asthmatic patients with exercise-induced asthma participated in a single-blind trial comparing the protective\\u000a effects of needle auricular acupuncture over the lung loci and those over the lumbago loci (serving as sham points). Effects\\u000a were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after running on a treadmill for 8 min. There

Olivia K. W. Chow; S. Y. So; W. K. Lam; D. Y. C. Yu; C. Y. Yeung

1983-01-01

186

Effect of an inhaled antihistamine on exercise-induced asthma  

Microsoft Academic Search

The ability of the H1 receptor antagonist clemastine to prevent exercise-induced asthma (EIA) has been studied in 10 adult asthmatic subjects. Exercise was performed for eight minutes on a cycle ergometer on two occasions on each of two days. The first test each day was without premedication and the second was preceded by inhalation of 0.05% clemastine or saline placebo

J P Hartley; S G Nogrady

1980-01-01

187

The effect of loratadine in exercise-induced asthma  

Microsoft Academic Search

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

A Baki; F Orhan

2002-01-01

188

Exercise-Induced Asthma in Adolescent Gym Class Population  

Microsoft Academic Search

The prevalence of exercise-induced asthma (ElA) was determined in a population of 12- and 13-year-old schoolchildren whose parents returned a questionnaire regarding a previous diagnosis of asthma, recent asthmatic symptoms and symptoms of allergic rhinitis. El A was defined as a >15% fall in peak expiratory flow rate (PEFR) following 6 min of free running in a gymnasium. Among the

Richard P. Bransford; Gail M. McNutt; Jordan N. Fink

1991-01-01

189

An unusual example of exercise-induced asthma  

Microsoft Academic Search

A patient with exercise-induced asthma is described in whom the post-exercise fall in F.E.V.1 was not prevented by the inhalation of isoprenaline immediately before exercise but was almost completely prevented by subcutaneous atropine given 40 minutes before exercise. A large fall in F.E.V.1 similar to the fall after exercise occurred after carbon dioxide-induced hyperventilation and voluntary hyperventilation performed at rest.

G. K. Crompton

1968-01-01

190

Effects of Inhaled Lidocaine on Exercise-Induced Asthma  

Microsoft Academic Search

Experiments were performed to determine if stimulation of afferent nerve endings in the respiratory mucosa plays a major role in the initiation of exercise-induced asthma. Five asthmatic subjects were studied in two sessions of 10 min treadmill exercise using an identical workload. In the control session the subjects were exercised without treatment; in the other session aerosol lidocaine (1.5 mg\\/kg)

W. Y. Chen; H. Chai

1987-01-01

191

Inhibition of exercise-induced asthma by different pharmacological pathways  

Microsoft Academic Search

Exercise-induced asthma (EIA) was provoked by standardized treadmill running for 6 minutes in 15 asthmatic children. The tests were carried out after the administration of a placebo, salbutamol, sodium cromoglycate, choline theophyllinate, and atrophine methonitrate aerosol in randomized fashion on different days. The mean post-exercise percent fall in peak expiratory flow rate was 45-2, 4-1, 19-6, 18-3, and 24-9 respectively.

S Godfrey; P König

1976-01-01

192

Exercise-induced anaphylaxis related to specific foods  

Microsoft Academic Search

We describe the case, documented by challenge results, of a 16-year-old girl with exercise-induced anaphylaxis associated with eating pizza and a cheese sandwich. Patients in whom a specific coprecipitating food has been identified should avoid it for at least 12 hours before exercise. All patients should be instructed to avoid eating 6 to 8 hours before exercise, discontinue exercise at

Stephen Tilles; Alan Schocket; Henry Milgrom

1995-01-01

193

Exercise-Induced growth hormone during acute sleep deprivation.  

PubMed

The effect of acute (24-h) sleep deprivation on exercise-induced growth hormone (GH) and insulin-like growth factor-1 (IGF-1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24-h sessions including a brief, high-intensity exercise bout following either a night of sleep (SLEEP) or (24-h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30-sec Wingate sprints on a cycle ergometer. Self-reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P = 0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P = 0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise-induced peak GH concentration (TTP), or free IGF-1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 ?g/L*min, P < 0.01), exercise-induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 ?g/L, P < 0.01) and ?GH (peak GH - resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 ?g/L, P < 0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise-induced GH response was significantly augmented in sleep-deprived individuals. PMID:25281616

Ritsche, Kevin; Nindl, Bradly C; Wideman, Laurie

2014-10-01

194

Metabolic response to light exercise after exercise-induced rhabdomyolysis  

Microsoft Academic Search

.   Inherent compromises in substrate metabolism, or impaired perfusion of muscle may contribute to the occurrence of exercise-induced\\u000a rhabdomyolysis. In this study, the lactate response of the elbow flexor muscles to light exercise was examined in eight subjects\\u000a (five males, three females) who previously demonstrated rhabdomyolysis with extreme swelling (ES; n=4) or no swelling (NS; n=4) of the upper arm

Stephen P. Sayers; Priscilla Clarkson; Jehangir J. Patel

2002-01-01

195

Exercise-induced neuromuscular dysfunction under reflex conditions  

Microsoft Academic Search

.   The purpose of this research was to describe further the effects of exercise-induced muscle damage on reflex sensitivity.\\u000a The subjects were eight physically active, but untrained males, between the ages of 18 and 29 years. The effects of eccentric\\u000a and concentric exercise on patellar tendon reflex responses were determined. The 8 week experiment consisted of two, 5 day,\\u000a test protocols with a

Thomas Kaufman; Jeanmarie R. Burke; Mark J. Davis; Larry J. Durstine

2001-01-01

196

Exercise-induced malignant hyperthermia in an English springer spaniel.  

PubMed

An exercise-induced malignant hyperthermia-like syndrome developed in an English Springer Spaniel. Moderate exercise resulted in pronounced hyperlactacidemia, dyspnea, and hyperthermia. Before exercise, the dog had high activities of serum muscle enzymes, mild reticulocytosis, abnormally increased erythrocyte osmotic fragility, and a positive result from the caffeine-halothane contracture test. This report supports the hypothesis of a canine stress syndrome and indicates a role for exercise/challenge tests in diagnosis of malignant hyperthermia susceptibility. PMID:3570952

Rand, J S; O'Brien, P J

1987-04-15

197

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

198

Wheat dependent exercise induced anaphylaxis: is this an appropriate terminology?  

Microsoft Academic Search

BackgroundThe presentation of wheat dependent exercise induced anaphylaxis (WDEIA) can be variable. A high index of clinical suspicion is required to initiate the investigation pathway. Double blind placebo controlled food-exercise challenge is the gold standard investigation but the practicality of this test limits its application.AimTo critically analyse the symptoms of WDEIA and their correlation with serum specific IgE (sIgE) to

G. K. Y. Wong; A. P. Huissoon; S. Goddard; D. M. Collins; M. T. Krishna

2010-01-01

199

How to explain exercise-induced phenotype from molecular data: rethink and reconstruction based on AMPK and mTOR signaling.  

PubMed

During endurance and resistance exercise training, AMPK and mTOR signaling were known as selective pathways implicating the differentiation of exercise-induced phenotype in skeletal muscle. Among the previous studies, however, the differences in exercise protocol, the individuality and the genetic heterogeneity within species make it difficult to reach a consistent conclusion in the roles of AMPK and mTOR signaling. In this review, we aim not to reanalyze the previous articles and present the research progress of AMPK and mTOR signaling in exercise, but to propose an abstract general hypothesis for exercise-induced phenotype. Generally, exercise- induced skeletal muscle phenotype is independent of one and a few genes, proteins and signaling pathways. Convergent adaptation will better summarize the specificity of skeletal muscle phenotype in response to a single mode of exercise. Backward adaptation will open a new concept to illustrate the process of exercise-induced adaptation, such as mitochondrial quality control and muscle mass homeostasis. PMID:24404437

Qi, Zhengtang; Zhai, Xiaofeng; Ding, Shuzhe

2013-01-01

200

The regulation of mitochondrial dynamics.  

PubMed

The structure of mitochondria is highly dynamic. Mitochondrial shape is cell-type specific and can be modified to meet changing requirements in energy production, calcium homeostasis, lipid biogenesis, fatty acid synthesis and other mitochondrial activities. This is achieved by modulating the dynamic properties of mitochondria including fusion, division, movement and positional tethering. It has become increasingly evident that mitochondrial dynamics also play an intimate role in several cellular signaling pathways and as such, many mechanisms have evolved to modulate mitochondrial structure. These regulatory mechanisms turn out to be important for modulation of mitochondrial-specific processes as well as cell, tissue and organism responses to developmental or environmental cues. PMID:24747170

Hoppins, Suzanne

2014-08-01

201

The Curious Question of Exercise-Induced Pulmonary Edema  

PubMed Central

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

2011-01-01

202

Pathophysiology of Acute Exercise-Induced Muscular Injury: Clinical Implications  

PubMed Central

Acute muscular injury is the most common injury affecting athletes and those participating in exercise. Nearly everyone has experienced soreness after unaccustomed or intense exercise. Clinically, acute strains and delayed-onset muscle soreness are very similar. The purpose of this paper is to review the predisposing factors, mechanisms of injury, structural changes, and biochemical changes associated with these injuries. Laboratory and clinical findings are discussed to help athletic trainers differentiate between the two conditions and to provide a background knowledge for evaluation, prevention, and treatment of exercise-induced muscular injury. PMID:16558305

Page, Phillip

1995-01-01

203

Food-dependent exercise-induced anaphylaxis: is wheat unique?  

PubMed

This review draws comparisons between wheat-dependent exercise-induced anaphylaxis (WDEIA) and other food-dependent exercise-induced anaphylaxis (FDEIAs) and discusses the importance of co-factors in its pathophysiology. FDEIA remains an enigmatic condition since it was first described 30 years ago. The sporadic and unpredictable nature of its reactions has puzzled clinicians and scientists for decades, but recent studies on WDEIA have enlightened us about the pathophysiology of this condition. The identification of defined allergic epitopes such as Tri a 19, ?-gliadin, ?-gliadin and ?-gliadin in WDEIA enables it to become the perfect model for studying FDEIA, but WDEIA is by no means a unique condition. On a larger scale, FDEIA represents a crucial link between IgE-mediated and anaphylactoid reactions and provides supportive evidence for the concept of 'summation anaphylaxis' and the need to overcome the 'allergen threshold'. Future work should focus on identifying more of the FDEIA epitopes and understanding their distinct molecular properties. The development of a biomarker in order to identify patients susceptible to co-factor influences would be invaluable. PMID:24127054

Wong, Gabriel K; Krishna, Mamidipudi T

2013-12-01

204

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

2013-11-01

205

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

2013-04-01

206

Acute versus chronic exercise-induced left-ventricular remodeling.  

PubMed

Exercise-induced cardiac remodeling (EICR) is the process by which the heart adapts to the physiologic stress of exercise. Non-invasive cardiovascular imaging has led to advances in the understanding of EICR, with sport-specific changes in left-ventricular (LV) structure and function being described; however, the majority of data stem from cross-sectional and short-duration longitudinal studies. Due to the paucity of long-term longitudinal EICR studies, the time course of this process and any distinct differentiation between acute and chronic adaptations remain largely unexplored. In order to clarify the natural history of EICR, longer duration longitudinal study is required. Such work will determine whether exercise-induced changes in myocardial structure and function occur in discrete stages. Examination of prolonged exposures to exercise training will also be necessary to determine normative values across the age and training spectrums of athletic patients. This information will help to distinguish the boundary between physiology and pathology in athletic patients. PMID:25300444

Weiner, Rory B; Baggish, Aaron L

2014-11-01

207

Short and longer-term effects of creatine supplementation on exercise induced muscle damage  

Microsoft Academic Search

The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo) participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo

John Rosene; Tracey Matthews; Christine Ryan; Keith Belmore; Alisa Bergsten; Jill Blaisdell; James Gaylord; Rebecca Love; Michael Marrone; Kristine Ward; Eric Wilson

2009-01-01

208

Exploring the Relationship between Exercise-Induced Arousal and Cognition Using Fractionated Response Time  

ERIC Educational Resources Information Center

Although a generally positive effect of acute exercise on cognitive performance has been demonstrated, the specific nature of the relationship between exercise-induced arousal and cognitive performance remains unclear. This study was designed to identify the relationship between exercise-induced arousal and cognitive performance for the central…

Chang, Yu-Kai; Etnier, Jennifer L.; Barella, Lisa A.

2009-01-01

209

Does deep water running reduce exercise-induced breast discomfort?  

PubMed Central

Aim To establish whether exercise?induced vertical breast displacement and discomfort in women with large breasts were reduced during deep water running compared to treadmill running. Methods Sixteen women (mean age ?=?32 years, range 19–43 years; mean mass ?=?74.1?kg, range 61–114?kg; mean height ?=?1.7?m, range 1.61–1.74?m), who were professionally sized to wear a C+ bra cup, were recruited as representative of women with large breasts. After extensive familiarisation, vertical breast motion of the participants was quantified as they ran at a self?selected stride rate on a treadmill and in 2.4?m deep water. Immediately after running, the subjects rated their breast discomfort and breast pain (visual analogue scale) and their perceived exertion (Borg scale). Breast discomfort, breast pain, perceived exertion, vertical breast displacement and vertical breast velocity were compared between the two experimental conditions. Results Exercise?induced breast discomfort was significantly less and perceived exertion was significantly greater during deep water running relative to treadmill running. Although there was no significant between?condition difference in vertical breast displacement, mean peak vertical breast velocity was significantly (p<0.05) less during deep water (upward mean (SD): 29.7 (14.0)?cm.s?1; downward: 31.1 (17.0)?cm.s?1) compared to treadmill running (upward mean (SD): 81.4 (21.7)?cm.s?1; downward: 100.0 (25.0)?cm.s?1). Conclusion Deep water running was perceived as a more strenuous but comfortable exercise mode for women with large breasts. Increased comfort was attributed to reduced vertical breast velocity rather than reduced vertical breast displacement. PMID:17535854

McGhee, Deirdre E; Steele, Julie R; Power, Bruce M

2007-01-01

210

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. PMID:21718247

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

2013-01-01

211

Metabolic response to light exercise after exercise-induced rhabdomyolysis.  

PubMed

Inherent compromises in substrate metabolism, or impaired perfusion of muscle may contribute to the occurrence of exercise-induced rhabdomyolysis. In this study, the lactate response of the elbow flexor muscles to light exercise was examined in eight subjects (five males, three females) who previously demonstrated rhabdomyolysis with extreme swelling (ES; n = 4) or no swelling (NS; n = 4) of the upper arm after eccentric exercise. Subjects performed identical light exercise bouts (45 s of rapid isotonic biceps curls consisting of both concentric and eccentric actions at 25% of maximum voluntary contraction force) using their previously eccentrically exercised arm (E-ARM) and control arm, which was not used previously to perform eccentric exercise (C-ARM). Blood lactate concentration ([La]b) was assessed 1.5, 3, 4.5, 6, and 9 min post-exercise. Peak [La]b and the area under the curve (AUC) were compared between the E-ARM of the ES and NS groups and between the C-ARM and E-ARM of the ES group. The AUC did not differ between the E-ARM of the ES and NS groups (P > 0.05) or between the C-ARM and E-ARM of the ES group (P > 0.05). In the ES group, the increase in [La]b after light exercise with the C-ARM [mean (SD) change, delta: 1.98 (0.7) mmol/l] was not different from the increase after exercising the E-ARM [delta: 2.10 (0.7) mmol/l; P>0.05]. Comparing the response of the E-ARM between groups, the increase in [La]b of the NS group [delta: 1.40 (0.4) mmol/l] was not different than that observed in the ES group [delta: 2.10 (0.7) mmol/l; P>0.05). Thus, subjects who had previously exhibited signs of exercise-induced rhabdomyolysis did not show an abnormal response to low-intensity anaerobic exercise. PMID:11990739

Sayers, Stephen P; Clarkson, Priscilla; Patel, Jehangir J

2002-01-01

212

Environmental temperature and exercise-induced blood oxidative stress.  

PubMed

Previous research findings indicate that environmental temperature can influence exercise-induced oxidative-stress responses, although the response to variable temperatures is unknown. The purpose of this study was to investigate the effect of warm, cold, and "neutral," or room, environmental temperatures on the blood oxidative stress associated with exercise and recovery. Participants (N = 12, age 27 ± 5 yr, VO2max = 56.7 ± 5.8 ml · kg-1 · min-1, maximal cycle power output = 300 ± 39 W) completed 3 exercise sessions consisting of a 1-hr ride at 60% Wmax, at 40% relative humidity in warm (33 °C), cold (7 °C), and room-temperature environments (20 °C) in a randomized crossover fashion. Rectal core temperature was monitored continually as participants remained in the respective trial temperature throughout a 3-hr recovery. Blood was collected preexercise and immediately, 1 hr, and 3 hr postexercise and analyzed for oxidative-stress markers including ferric-reducing ability of plasma (FRAP), Trolox-equivalent antioxidant capacity (TEAC), lipid hydroperoxides, and protein carbonyls. Core temperature was significantly elevated by all exercise trials, but recovery core temperatures reflected the given environment. FRAP (p < .001), TEAC (p < .001), and lipid hydroperoxides (p < .001) were elevated after warm exercise while protein carbonyls were not altered (p > .05). These findings indicate that moderate-intensity exercise and associated recovery in a warm environment elicits a blood oxidative-stress response not observed at comparable exercise performed at lower temperatures. PMID:23532145

Quindry, John; Miller, Lindsey; McGinnis, Graham; Kliszczewiscz, Brian; Slivka, Dustin; Dumke, Charles; Cuddy, John; Ruby, Brent

2013-04-01

213

Provocation by eucapnic voluntary hyperpnoea to identify exercise induced bronchoconstriction  

PubMed Central

The International Olympic Committee Medical Commission (IOC-MC) requires notification for use of a ß2 agonist at the Winter Olympic Games in Salt Lake City. This notification will be required seven days before the event and must be accompanied by objective evidence that justifies the need to use one. The IOC-MC has expressed the viewpoint that, at present, eucapnic voluntary hyperpnoea (EVH) is the optimal laboratory challenge to confirm that an athlete has exercise induced bronchoconstriction (EIB). The EVH test recommended was specifically designed to identify EIB. EVH has been performed in thousands of subjects in both the laboratory and the field. The test requires the subject to hyperventilate dry air containing 5% carbon dioxide at room temperature for six minutes at a target ventilation of 30 times the subject's forced expiratory volume in one second (FEV1). The test conditions can be modified to simulate the conditions that give the athlete their symptoms with exercise. A reduction in FEV1 of 10% or more of the value before the test is considered positive. Key Words: hyperpnoea; bronchial provocation; exercise PMID:11579071

Anderson, S; Argyros, G; Magnussen, H; Holzer, K

2001-01-01

214

Lycium barbarum Polysaccharides Reduce Exercise-Induced Oxidative Stress  

PubMed Central

The purpose of the present study was to investigate the effects of Lycium barbarum polysaccharides (LBP) on exercise-induced oxidative stress in rats. Rats were divided into four groups, i.e., one control group and three LBP treated groups. The animals received an oral administration of physiological saline or LBP (100, 200 and 400 mg/kg body weight) for 28 days. On the day of the exercise test, rats were required to run to exhaustion on the treadmill. Body weight, endurance time, malondialdehyde (MDA), super oxide dismutase (SOD) and glutathione peroxidase (GPX) level of rats were measured. The results showed that the body weight of rats in LBP treated groups were not significantly different from that in the normal control group before and after the experiment (P > 0.05). After exhaustive exercise, the mean endurance time of treadmill running to exhaustion of rats in LBP treated groups were significantly prolonged compared with that in the normal control group. MDA levels of rats in LBP treated groups were significantly decreased compared with that in the normal control group (P < 0.05). SOD and GPX levels of rats in LBP treated groups were significantly increased compared with that in the normal control group (P < 0.05). Together, these results indicate that LBP was effective in preventing oxidative stress after exhaustive exercise. PMID:21541044

Shan, Xiaozhong; Zhou, Junlai; Ma, Tao; Chai, Qiongxia

2011-01-01

215

Conserved roles of Sam50 and metaxins in VDAC biogenesis.  

PubMed

Voltage-dependent anion-selective channel (VDAC) is a beta-barrel protein in the outer mitochondrial membrane that is necessary for metabolite exchange with the cytosol and is proposed to be involved in certain forms of apoptosis. We studied the biogenesis of VDAC in human mitochondria by depleting the components of the mitochondrial import machinery by using RNA interference. Here, we show the importance of the translocase of the outer mitochondrial membrane (TOM) complex in the import of the VDAC precursor. The deletion of Sam50, the central component of the sorting and assembly machinery (SAM), led to both a strong defect in the assembly of VDAC and a reduction in the steady-state level of VDAC. Metaxin 2-depleted mitochondria had reduced levels of metaxin 1 and were deficient in import and assembly of VDAC and Tom40, but not of three matrix-targeted precursors. We also observed a reduction in the levels of metaxin 1 and metaxin 2 in Sam50-depleted mitochondria, implying a connection between these three proteins, although Sam50 and metaxins seemed to be in different complexes. We conclude that the pathway of VDAC biogenesis in human mitochondria involves the TOM complex, Sam50 and metaxins, and that it is evolutionarily conserved. PMID:17510655

Kozjak-Pavlovic, Vera; Ross, Katharina; Benlasfer, Nouhad; Kimmig, Sonja; Karlas, Alexander; Rudel, Thomas

2007-06-01

216

Nitric oxide regulates vascular adaptive mitochondrial dynamics  

PubMed Central

Cardiovascular disease risk factors, such as diabetes, hypertension, dyslipidemia, obesity, and physical inactivity, are all correlated with impaired endothelial nitric oxide synthase (eNOS) function and decreased nitric oxide (NO) production. NO-mediated regulation of mitochondrial biogenesis has been established in many tissues, yet the role of eNOS in vascular mitochondrial biogenesis and dynamics is unclear. We hypothesized that genetic eNOS deletion and 3-day nitric oxide synthase (NOS) inhibition in rodents would result in impaired mitochondrial biogenesis and defunct fission/fusion and autophagy profiles within the aorta. We observed a significant, eNOS expression-dependent decrease in mitochondrial electron transport chain (ETC) protein subunits from complexes I, II, III, and V in eNOS heterozygotes and eNOS null mice compared with age-matched controls. In response to NOS inhibition with NG-nitro-l-arginine methyl ester (l-NAME) treatment in Sprague Dawley rats, significant decreases were observed in ETC protein subunits from complexes I, III, and IV as well as voltage-dependent anion channel 1. Decreased protein content of upstream regulators of mitochondrial biogenesis, cAMP response element-binding protein and peroxisome proliferator-activated receptor-? coactivator-1?, were observed in response to 3-day l-NAME treatment. Both genetic eNOS deletion and NOS inhibition resulted in decreased manganese superoxide dismutase protein. l-NAME treatment resulted in significant changes to mitochondrial dynamic protein profiles with decreased fusion, increased fission, and minimally perturbed autophagy. In addition, l-NAME treatment blocked mitochondrial adaptation to an exercise intervention in the aorta. These results suggest that eNOS/NO play a role in basal and adaptive mitochondrial biogenesis in the vasculature and regulation of mitochondrial turnover. PMID:23585138

Miller, Matthew W.; Knaub, Leslie A.; Olivera-Fragoso, Luis F.; Keller, Amy C.; Balasubramaniam, Vivek; Watson, Peter A.

2013-01-01

217

Exercise induced skeletal muscle metabolic stress is reduced after pulmonary rehabilitation in COPD.  

PubMed

In COPD, skeletal muscle ATP resynthesis may be insufficient to meet demand during exercise due to excessive anaerobic and reduced oxidative (mitochondrial) energy production, leading to metabolic stress. We investigated the effect of outpatient pulmonary rehabilitation (PR) on the metabolic response (measured by exercise-induced accumulation of plasma ammonia) and determined whether this response predicted functional improvement following PR. 25 subjects with stable COPD [mean (SD) age 67 (8)years and FEV(1) 47 (18)% predicted] performed maximal cycling ergometry before and after PR. Plasma ammonia was measured at rest, during exercise and 2 min post-exercise. Following PR, there were significant increases in peak cycle WR and ISWT performance (Mean (SEM) changes 13.1 (2.0) W and 93 (15) m respectively, p < 0.001). Mean (SEM) rise in plasma ammonia was reduced at peak (Pre vs Post-PR: 29.0 (4.5) vs 20.2 (2.5) ?mol/l, p < 0.05) and isotime (Pre vs Post-PR: 29.0 (4.5) vs 10.6 (1.7) ?mol/l, p < 0.001) exercise. Improvements in exercise performance after PR were similar among subgroups who did versus those who did not show a rise in ammonia at baseline. The results suggest that muscle cellular energy production was better matched to the demands of exercise following PR. We conclude that a pragmatic outpatient PR programme involving high intensity walking exercise results in significant adaptation of the skeletal muscle metabolic response with a reduction in exercise-related metabolic stress. However, the outcome of PR could not be predicted from baseline metabolic response. PMID:21036584

Calvert, Lori D; Singh, Sally J; Morgan, Michael D; Steiner, Michael C

2011-03-01

218

Eosinophil influx into the airways in patients with exercise-induced asthma  

Microsoft Academic Search

Exercise-induced asthma is a common phenomenon, the mechanism of which is undetermined. Eosinophils have been suggested as playing a role in its occurrence. We studied the effect of exercise-induced asthma on the cellular and mediator composition of spontaneously obtained sputum.Twenty-five patients with bronchial asthma were investigated by studying sputum spontaneously obtained before and following challenge. One group with (n=9) and

S. KIVITY; A. ARGAMAN; A. ONN; Y. SHWARTZ; A. MAN; J. GREIF; E. FIREMAN

2000-01-01

219

Heat and Water Loss from the Airways and Exercise-Induced Asthma  

Microsoft Academic Search

Exercise-induced asthma was studied in 8 asthmatics using various conditions of inspired air during exercise. The exercise consisted of walking on a treadmill for 10 min, with a speed and grade elevation adjusted to achieve the target heart rate of approximately 90 % of predicted maximum. Pulmonary function tests were performed pre- and post-exercise to determine exercise-induced asthma. With inspired

W. Y. Chen; D. J. Horton

1977-01-01

220

Effects of cold water immersion on the symptoms of exercise-induced muscle damage  

Microsoft Academic Search

Cryotherapy is an effective treatment for acute sports injury to soft tissue, although the effect of cryotherapy on exercise-induced muscle damage is unclear. The aim of this study was to assess the effects of cold water immersion on the symptoms of exercise-induced muscle damage following strenuous eccentric exercise. After performing a bout of damage-inducing eccentric exercise (eight sets of five

ROGER ESTON; DANIEL PETERS

1999-01-01

221

Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis  

Microsoft Academic Search

Nedocromil sodium in the treatment of exercise-induced asthma: a meta-analysis. C. Spooner, B.H. Rowe, L.D. Saunders. #ERS Journals Ltd 2000. ABSTRACT: Exercise-induced asthma (or bronchoconstriction) afflicts millions of people worldwide. While generally self-limiting, it can hinder performance and reduce activity levels, thus it is an important condition to diagnose and treat. The objective of this review was to assess the

C. Spooner; B. H. Rowe; L. D. Saunders

2000-01-01

222

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

2013-07-01

223

Assessment and prevention of exercise-induced bronchoconstriction.  

PubMed

The assessment of exercise-induced bronchoconstriction (EIB) in athletes requires the measurement of forced expiratory volume in 1 s (FEV(1)) before and after vigorous exercise or a surrogate of exercise such as eucapnic voluntary hyperpnoea (EVH) of dry air or mannitol dry powder. Exercise testing in a laboratory has a low sensitivity to identify EIB, and exercise testing in the field can be a challenge in itself particularly in cold weather athletes. The EVH test requires the subject to ventilate dry air containing ?5% CO(2) for 6 min through a low-resistance circuit at a rate higher than that usually achieved on maximum exercise. A ?10% reduction in FEV(1) is a positive response to exercise and EVH and, when sustained, is usually associated with release of inflammatory mediators of broncho constriction. Another surrogate, mannitol dry powder, given by inhalation in progressively increasing doses, is used to mimic the dehydrating stimulus of exercise hyperpnoea. A positive mannitol test is a 15% fall in FEV(1) at ?635 mg and reveals potential for EIB. Mannitol has a high specificity for identifying a clinical diagnosis of asthma. Once a diagnosis of EIB is established, the athlete needs to know how to avoid EIB. Being treated daily with an inhaled corticosteroid to reduce airway inflammation, inhaling a ?(2) agonist or a cromone immediately before exercise, or taking a leukotriene antagonist several hours before exercise, all inhibit or prevent EIB. Other strategies include warming up prior to exercise and reducing respiratory water and heat loss by using face masks or nasal breathing. PMID:22247297

Anderson, Sandra D; Kippelen, Pascale

2012-05-01

224

Quantification of exercise-induced pulmonary haemorrhage with bronchoalveolar lavage.  

PubMed

Exercise-induced pulmonary haemorrhage (EIPH) causes serious economic losses in the horse racing industry. Endoscopic examination indicates that 40-90% of horses exhibit EIPH following sprint exercise, but the limitations of the endoscope prevent diagnosis in many horses. Bronchoalveolar lavage (BAL) was utilised to detect red blood cells (RBCs) in the terminal airways in 6 horses. Two lavages were performed at weekly intervals prior to exercise, one within 90 min after exercise, and 5 at weekly intervals after exercise. The horses were exercised strenuously at 12.5-14.6 m/s on a treadmill (3 degree incline). Heart rates ranged from 192-207 beats/min, and mean pulmonary arterial pressures (mPAP) ranged from 80-102 mmHg. Neither epistaxis nor endoscopic evidence of EIPH was seen in any of the 6 horses following exercise. However, the number of RBCs in the lavage fluid increased significantly over control values immediately after exercise in all horses but returned to control values by one week after exercise. Haemosiderophages in the BAL fluid did not increase until one week after exercise and remained elevated for 3 weeks after exercise. Twenty per cent of the total population of alveolar macrophages contained haemosiderin. A positive relationship occurred between the number of RBCs in the lavage fluid and mPAP; the amount of haemorrhage increased as the mPAP exceeded 80 to 90 mmHg. The results with BAL used as the diagnostic tool, suggest that all strenuously exercised horses may exhibit EIPH; the amount of haemorrhage appears to be associated with the magnitude of the high pulmonary arterial pressure. PMID:9705109

Meyer, T S; Fedde, M R; Gaughan, E M; Langsetmo, I; Erickson, H H

1998-07-01

225

Identification of human exercise-induced myokines using secretome analysis.  

PubMed

Endurance exercise is associated with significant improvements in cardio-metabolic risk parameters. A role for myokines has been hypothesized, yet limited information is available about myokines induced by acute endurance exercise in humans. Therefore, the aim of the study was to identify novel exercise-induced myokines in humans. To this end, we carried out a 1 h one-legged acute endurance exercise intervention in 12 male subjects and a 12 wk exercise training intervention in 18 male subjects. Muscle biopsies were taken before and after acute exercise or exercise training and were subjected to microarray-based analysis of secreted proteins (secretome). For acute exercise, secretome analysis resulted in a list of 86 putative myokines, which was reduced to 29 by applying a fold-change cut-off of 1.5. Based on that shortlist, a selection of putative myokines was measured in the plasma by ELISA or multiplex assay. From that selection, CX3CL1 (fractalkine) and CCL2 (MCP-1) increased at both mRNA and plasma levels. From the known myokines, only IL-6 and FGF 21 changed at the mRNA level, whereas none of the known myokines changed at the plasma level. Secretome analysis of exercise training intervention resulted in a list of 69 putative myokines. Comparing putative myokines altered by acute exercise and exercise training revealed a limited overlap of only 13 genes. In conclusion, this study identified CX3CL1 and CCL2 as myokines that were induced by acute exercise at the gene expression and plasma level and that may be involved in communication between skeletal muscle and other organs. PMID:24520153

Catoire, Milène; Mensink, Marco; Kalkhoven, Eric; Schrauwen, Patrick; Kersten, Sander

2014-04-01

226

Exercise-induced hypoxemia in athletes: role of inadequate hyperventilation.  

PubMed

These experiments examined the exercise-induced changes in pulmonary gas exchange in elite endurance athletes and tested the hypothesis that an inadequate hyperventilatory response might explain the large intersubject variability in arterial partial pressure of oxygen (PaO2) during heavy exercise in this population. Twelve highly trained endurance cyclists [maximum oxygen consumption (VO2max) range = 65-77 ml.kg-1.min-1] performed a normoxic graded exercise test on a cycle ergometer to VO2max at sea level. During incremental exercise at VO2max, 5 of the 12 subjects had ideal alveolar to arterial PO2 gradients (PA-aO2) of above 5 kPa (range 5-5.7) and a decline from resting PaO2 (delta PaO2) 2.4 kPa or above (range 2.4-2.7). In contrast, 4 subjects had a maximal exercise PA-aO2 of 4.0-4.3 kPa with delta PaO2 of 0.4-1.3 kPa while the remaining 3 subjects had PA-aO2 of 4.3-5 kPa with delta PaO2 between 1.7 and 2.0 kPa. The correlation between PAO2 and PaO2 at VO2max was 0.17. Further, the correlation between the ratio of ventilation to oxygen consumption vs PaO2 and arterial partial pressure of carbon dioxide vs PaO2 at VO2max was 0.17 and 0.34, respectively. These experiments demonstrate that heavy exercise results in significantly compromised pulmonary gas exchange in approximately 40% of the elite endurance athletes studied. These data do not support the hypothesis that the principal mechanism to explain this gas exchange failure is an inadequate hyperventilatory response. PMID:1505538

Powers, S K; Martin, D; Cicale, M; Collop, N; Huang, D; Criswell, D

1992-01-01

227

Exercise-induced hypoalgesia - interval versus continuous mode.  

PubMed

Aerobic exercise at approximately 70% of maximal aerobic capacity moderately reduces pain sensitivity and attenuates pain, even after a single session. If the analgesic effects depend on exercise intensity, then high-intensity interval exercise at 85% of maximal aerobic capacity should further reduce pain. The aim of this study was to explore the exercise-induced analgesic effects of high-intensity interval aerobic exercise and to compare them with the analgesic effects of moderate continuous aerobic exercise. Twenty-nine young untrained healthy males were randomly assigned to aerobic-continuous (70% heart rate reserve (HRR)) and interval (4 × 4 min at 85% HRR and 2 min at 60% HRR between cycles) exercise modes, each lasting 30 min. Psychophysical pain tests, pressure and heat pain thresholds (HPT), and tonic heat pain (THP) were conducted before and after exercise sessions. Repeated measures ANOVA was used for data analysis. HPT increased (p = 0.056) and THP decreased (p = 0.013) following exercise unrelated to exercise type. However, the main time effect (pre-/postexercise) was a trend of increased HPT (45.6 ± 1.9 °C to 46.2 ± 1.8 °C; p = 0.082) and a significant reduction in THP (from 50.7 ± 25 to 45.9 ± 25.4 numeric pain scale; p = 0.043) following interval exercise. No significant change was found for the pressure pain threshold following either exercise type. In conclusion, interval exercise (85% HRR) has analgesic effects on experimental pain perception. This, in addition to its cardiovascular, muscular, and metabolic advantages may promote its inclusion in pain management programs. PMID:24773287

Kodesh, Einat; Weissman-Fogel, Irit

2014-07-01

228

Intensity Thresholds for Aerobic Exercise-Induced Hypoalgesia  

PubMed Central

Despite many studies investigating exercise-induced hypoalgesia, there is limited understanding of the optimal intensity of aerobic exercise in producing hypoalgesic effects across different types of pain stimuli. Given that not all individuals are willing or capable of engaging in high intensity aerobic exercise, whether moderate intensity aerobic exercise is associated with a hypoalgesic response and whether this response generalizes to multiple pain induction techniques needs to be substantiated. Purpose This study’s purpose is to test for differences in the magnitude of pressure and heat pain modulation induced by moderate (MAE) and vigorous (VAE) intensity aerobic exercise. Methods Twelve healthy young males and 15 females completed one training session and three testing sessions consisting of 25 minutes of either 1) stationary cycling at 70% heart rate reserve (HRR), 2) stationary cycling at 50% HRR, or 3) quiet rest (control). Pain testing was conducted on both forearms prior to and immediately following each condition and included the following tests: pressure pain thresholds (PPT), suprathreshold pressure pain test, static continuous heat test, and repetitive pulse heat pain test. Repeated measures ANOVAs were conducted on each pain measure. Results VAE and MAE reduced pain ratings during static continuous heat stimuli and repetitive heat pulse stimuli, with VAE producing larger effects. VAE also increased PPTs, while neither exercise influenced suprathreshold pressure pain ratings. Conclusion These results suggest that MAE is capable of producing a hypoalgesic effect using continuous and repetitive pulse heat stimuli. However, a dose-response effect was evident as VAE produced larger effects than MAE. PMID:24002342

Naugle, Kelly M.; Naugle, Keith E.; Fillingim, Roger B.; Samuels, Brian; Riley, Joseph L.

2014-01-01

229

Mitochondrial dysfunction in heart failure  

PubMed Central

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 cylic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction. PMID:22948484

Rosca, Mariana G.; Hoppel, Charles L.

2013-01-01

230

Organelle biogenesis and interorganellar connections  

PubMed Central

Membrane contact sites (MCSs) allow the exchange of molecules and information between organelles, even when their membranes cannot fuse directly. In recent years, a number of functions have been attributed to these contacts, highlighting their critical role in cell homeostasis. Although inter-organellar connections typically involve the endoplasmic reticulum (ER), we recently reported the presence of a novel MCSs between melanosomes and mitochondria. Melanosome-mitochondrion contacts appear mediated by fibrillar bridges resembling the protein tethers linking mitochondria and the ER, both for their ultrastructural features and the involvement of Mitofusin 2. The frequency of these connections correlates spatially and timely with melanosome biogenesis, suggesting a functional link between the 2 processes and in general that organelle biogenesis in the secretory pathway requires interorganellar crosstalks at multiple steps. Here, we summarize the different functions attributed to MCSs, and discuss their possible relevance for the newly identified melanosome-mitochondrion liaison. PMID:25346798

Daniele, Tiziana; Schiaffino, Maria Vittoria

2014-01-01

231

Pharmacological approaches to restore mitochondrial function  

PubMed Central

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders, but is 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 a range of diseases, which has spurred active drug discovery efforts in this area. PMID:23666487

Andreux, Penelope A.; Houtkooper, Riekelt H.; Auwerx, Johan

2014-01-01

232

The preventive effect and duration of action of two doses of inhaled furosemide on exercise-induced asthma in children  

Microsoft Academic Search

Background: Exercise-induced asthma can be prevented by treatment with inhaled furosemide. Objective: In this study we evaluated the effect and duration of action of two doses (15 and 30 mg) of inhaled furosemide in prevention of exercise-induced asthma in children. Methods: Ten children with exercise-induced asthma (8 boys and 2 girls, aged 6 to 13 years) were included in the

Elio Novembre; Gianfranco Frongia; Enrico Lombardi; Massimo Resti; Enrico Zammarchi; Alberto Vierucci

1995-01-01

233

Mitochondrial Metabolic Reprogramming Induced by Calorie Restriction  

PubMed Central

Abstract Significance: Calorie restriction (CR) is a known intervention that delays most aging processes. Most of the beneficial effects of CR are mediated by improved maintenance of mitochondrial performance in aged individuals. The control of mitochondrial biogenesis, apoptosis, and protein turnover is required for healthy aging. CR is able to induce molecular mechanisms that preserve oxidative capacity and decrease oxidative damage. Recent Advances and Critical Issues: Published data indicate that peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1?) is activated in old animals under CR conditions compared to ad libitum counterparts, enhancing mitochondrial biogenesis. Molecular regulation of PGC-1? has recently attracted significant research interest. We discuss the master regulators of energy metabolism such as AMP-activated protein kinase and sirtuin 1 among others that have been demonstrated to activate mitochondrial biogenesis through increased PGC-1? activity at transcriptional and post-translational levels. Additionally, we describe the latest findings that explain how CR promotes mitochondrial efficiency and decreases mitochondrial-derived oxidative damage. Future Directions: Understanding the beneficial mitochondrial changes conferred by CR will aid design of therapies for age-related diseases and help slow the aging process. Given the difficulty for humans to adhere to CR, we also explore new molecules that have been proposed during the last years to mimic the CR phenotype and their potential as future therapeutics. Antioxid. Redox Signal. 19, 310–320. PMID:22901095

Martin-Montalvo, Alejandro

2013-01-01

234

PGC-1?/? induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders  

PubMed Central

Members of the peroxisome proliferator-activated receptor ? coactivator (PGC) family are potent inducers of mitochondrial biogenesis. We have tested the potential effect of increased mitochondrial biogenesis in cells derived from patients harboring oxidative phosphorylation defects due to either nuclear or mitochondrial DNA mutations. We found that the PGC-1? and/or PGC-1? expression improved mitochondrial respiration in cells harboring a complex III or IV deficiency as well as in transmitochondrial cybrids harboring mitochondrial encephalomyopathy lactic acidosis and stroke A3243G tRNA(Leu)UUR gene mutation. The respiratory function improvement was found to be associated with increased levels of mitochondrial components per cell, although this increase was not homogeneous. These results reinforce the concept that increased mitochondrial biogenesis is a promising venue for the treatment of mitochondrial diseases. PMID:19297390

Srivastava, Sarika; Diaz, Francisca; Iommarini, Luisa; Aure, Karine; Lombes, Anne; Moraes, Carlos T.

2009-01-01

235

Mitochondrial quality control systems sustain brain mitochondrial bioenergetics in early stages of type 2 diabetes.  

PubMed

Mitochondria have a crucial role in the supply of energy to the brain. Mitochondrial alterations can lead to detrimental consequences on the function of brain cells and are thought to have a pivotal role in the pathogenesis of several neurologic disorders. This study was aimed to evaluate mitochondrial function, fusion-fission and biogenesis and autophagy in brain cortex of 6-month-old Goto-Kakizaki (GK) rats, an animal model of nonobese type 2 diabetes (T2D). No statistically significant alterations were observed in mitochondrial respiratory chain and oxidative phosphorylation system. A significant decrease in the protein levels of OPA1, a protein that facilitates mitochondrial fusion, was observed in brain cortex of GK rats. Furthermore, a significant decrease in the protein levels of LC3-II and a significant increase in protein levels of mTOR phosphorylated at serine residue 2448 were observed in GK rats suggesting a suppression of autophagy in diabetic brain cortex. No significant alterations were observed in the parameters related to mitochondrial biogenesis. Altogether, these results demonstrate that during the early stages of T2D, brain mitochondrial function is maintained in part due to a delicate balance between mitochondrial fusion-fission and biogenesis and autophagy. However, future studies are warranted to evaluate the role of mitochondrial quality control pathways in late stages of T2D. PMID:24833464

Santos, R X; Correia, S C; Alves, M G; Oliveira, P F; Cardoso, S; Carvalho, C; Seiça, R; Santos, M S; Moreira, P I

2014-09-01

236

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. PMID:20523788

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

2009-01-01

237

Exercise training and immune crosstalk in breast cancer microenvironment: exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines  

PubMed Central

Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms are proposed. The first considers the host immune response as modifiable by aerobic exercise training. This exercise-modulated immune-tumor crosstalk in the mammary microenvironment may alter the balance between tumor initiation and progression versus tumor suppression. The second paradigm considers the beneficial role of exercise-induced, skeletal muscle-derived cytokines, termed “myokines”. These myokines exert endocrine-like effects on multiple organs, including the mammary glands. In this systematic review, we i) define the role of macrophages and T-cells in breast cancer initiation and progression; ii) address the two paradigms that support exercise-induced immunomodulation; iii) systematically assessed the literature for exercise intervention that assessed biomarkers relevant to both paradigms in human intervention trials of aerobic exercise training, in healthy women and women with breast cancer; iv) incorporated pre-clinical animal studies and non-RCTs for background discussion of putative mechanisms, through which aerobic exercise training modulates the immunological crosstalk, or the myokine-tumor interaction in the tumor microenvironment; and v) speculated on the potential biomarkers and mechanisms that define an exercise-induced, anti-tumor “signature”, with a view toward developing relevant biomarkers for future aerobic exercise intervention trials. PMID:25360210

Goh, Jorming; Niksirat, Negin; Campbell, Kristin L

2014-01-01

238

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. PMID:21982713

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

2011-01-01

239

The Effect of Exhausting Exercise Induced Fatigue on the Double-Leg Balance ofElite Male Athletes  

Microsoft Academic Search

Problem statement: Fatigue is a complex phenomenon that can be descri bed as a time- dependent exercise-induced reduction in the maximal force generating capacity of a muscle. The aim of the present study was to examine the effect of e xhausting exercise induced fatigue on the double-le g balance of elite male athletes. Approach: This study included 30 apparently healthy

Khodadad Letafatkar; Mohammad Hossein Alizadeh; Mohammad Reza Kordi

2009-01-01

240

Oral contraceptive use and exercise-induced muscle damage and recovery  

Microsoft Academic Search

Endogenous estrogen appears to attenuate muscle damage in animals; however, similar evidence in humans is not as strong. This investigation tested the hypothesis that women taking oral contraceptives, thereby having higher exogenous estrogen levels, would be more susceptible to damage or have an attenuated recovery from exercise-induced muscle damage. Muscle damage in women taking combined estrogen and progesterone oral contraceptives

Kathleen J Savage; Priscilla M Clarkson

2002-01-01

241

Sample size estimation in studies monitoring exercise-induced bronchoconstriction in asthmatic children  

Microsoft Academic Search

BACKGROUND: The repeatability of the response to standardised treadmill exercise testing using dry air and monitoring of heart rate in asthmatic children suffering from exercise-induced bronchoconstriction (EIB) has not been well established. METHODS: Twenty seven asthmatic children with known EIB performed standardised exercise testing twice within a period of three weeks. The tests were performed on a treadmill while breathing

W. B. Hofstra; J. K. Sont; P. J. Sterk; H. J. Neijens; M. C. Kuethe; E. J. Duiverman

1997-01-01

242

Catecholamines and cyclic AMP in allergic and exercise induced asthma of childhood  

Microsoft Academic Search

In order to provoke exercise induced asthma (EIA) a test which involved running for 7 min was performed with 21 asthmatic children. Eleven children not only developed a highly significant increase in airway resistance (Rt), but showed also a 4-fold increase in plasma noradrenaline (NA) levels. In 10 children who did not develop EIA only a 1.5-fold increase of NA

D. Reinhardt; M. Nagel; E. A. Stemmann; F. Wegner

1980-01-01

243

Time Course of Effect of Disodium Cromoglycate on Exercise-induced Asthma  

Microsoft Academic Search

Exercise tests, consisting of 6 minutes of continuous running, were performed on 10 asthmatic children known to develop exercise-induced bronchoconstriction. Disodium cromoglycate was equally effective in preventing post-exercise bronchoconstriction, whether given 20 minutes before or immediately before exercise. There was a small but significant effect when it was administered at the end of exercise. No placebo effect was noted. Bronchodilatation

M. Silverman; Tina Andrea

1972-01-01

244

A mask to modify inspired air temperature and humidity and its effect on exercise induced asthma  

Microsoft Academic Search

BACKGROUND: Heat and moisture loss from the respiratory tract during exercise are important triggers of exercise induced asthma. METHODS: A new heat and moisture exchange mask has been developed which both recovers exhaled heat and water and has a sufficiently low resistance for use during exercise. The effect of the mask on inspired air temperature was studied in four normal

M Nisar; D P Spence; J Haycock; Y Jones; M J Walshaw; J E Earis; P M Calverley; M G Pearson

1992-01-01

245

Dose-response study of nebulised nedocromil sodium in exercise induced asthma  

Microsoft Academic Search

Ten patients with exercise induced asthma, in whom inhaled nedocromil sodium 4 mg by metered dose inhaler attenuated the exercise fall in forced expiratory volume in one second (FEV1) by at least 40%, participated in a double blind dose response study to compare the protective effect of nedocromil sodium given 15 minutes before exercise challenge via a nebuliser (Wright) in

M K Albazzaz; M G Neale; K R Patel

1989-01-01

246

Exercise-induced asthma in children: a marker of airway inflammation  

Microsoft Academic Search

What we know ? Exercise-induced asthma (EIA) occurs in up to 23% of schoolchildren. ? In 40% of children with demonstrable EIA, no clinical diagnosis of asthma has been made. ? Children with asthma and EIA have eosinophils in their sputum, consistent with active asthma. ? EIA is well controlled in 50%-65% of children with moderate to severe asthma, so

Sandra D Anderson

2002-01-01

247

Cromolyn versus nedocromil: Duration of action in exercise-induced asthma in children  

Microsoft Academic Search

Cromolyn sodium (10 mg), nedocromil sodium (4 mg), and placebo, all delivered by a metered dose inhaler, were compared in their efficacy and duration of action in preventing exercise-induced asthma in children. After a screening test was performed, 13 patients with asthma performed standard exercise tests 20 minutes and 140 minutes after drug inhalation in a randomized, double-blind, crossover study.

Fernando M. de Benedictis; Gianluca Tuteri; Paola Pazzelli; Alberto Bertotto; Lucio Bruni; Renato Vaccaro

1995-01-01

248

Circulating adrenaline and noradrenaline concentrations during exercise in patients with exercise induced asthma and normal subjects  

Microsoft Academic Search

A failure of the usual increase in plasma adrenaline and noradrenaline concentrations during submaximal exercise has been suggested as a contributory cause of exercise induced asthma. Six normal subjects and six asthmatic patients underwent a standard graded maximal exercise test. Measurements of oxygen consumption, minute ventilation, exercise time, blood lactate concentration, and heart rate indicated that the two groups achieved

K E Berkin; G Walker; G C Inglis; S G Ball; N C Thomson

1988-01-01

249

Exercise Challenge for Exercise-Induced Bronchospasm. Confirming Presence, Evaluating Control.  

ERIC Educational Resources Information Center

Exercise-induced bronchospasm commonly strikes young people, keeping many away from activity. The exercise challenge test (a powerful tool in diagnosing the condition, fine-tuning treatment, and improving patient compliance) can help get patients back in action. Knowing how to interpret and use test results helps physicians expedite effective…

Kaplan, Ted A.

1995-01-01

250

Reduction of exercise-induced asthma in children by short, repeated warm ups  

Microsoft Academic Search

AIM: To study the effect of a warm up schedule on exercise-induced asthma in asthmatic children to enable them to engage in asthmogenic activities. METHOD: In the first study, peak flows during and after three short, repeated warm up schedules (SRWU 1, 2, and 3), identical in form but differing in intensity, were compared in 16 asthmatic children. In the

C. de Bisschop; H. Guenard; P. Desnot; J. Vergeret

1999-01-01

251

Dose-response effect of sodium cromoglycate pressurised aerosol in exercise induced asthma  

Microsoft Academic Search

The effects of 2, 10, and 20 mg of sodium cromoglycate delivered by aerosol were compared with those of placebo in a double blind study in 11 patients with extrinsic and exercise induced asthma. The effect of nebulised sodium cromoglycate delivered through a Wright nebuliser (estimated dose 12 mg) was also studied. Patients exercised on a treadmill for six to

W M Tullett; K M Tan; R T Wall; K R Patel

1985-01-01

252

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

253

The Roles of Testosterone and Alpha-Amylase in Exercise-Induced Sexual Arousal in Women  

E-print Network

; Alpha-Amylase Introduction Dynamic, cardiovascular exercise has many well-documented health benefits. One of the lesser known benefits is the positive effect of acute exercise on female sexual arousalThe Roles of Testosterone and Alpha-Amylase in Exercise-Induced Sexual Arousal in Women Lisa Dawn

Meston, Cindy

254

Update on Exercise-Induced Asthma. A Report of the Olympic Exercise Asthma Summit Conference.  

ERIC Educational Resources Information Center

Summarizes results from the Olympic Exercise Asthma Summit Conference, offering the latest on identifying and managing exercise-induced asthma (EIA). Concludes that effective pharmacologic and nonpharmacologic treatment is available, but EIA is underrecognized and underdiagnosed. Physicians should look for it in all patients, including school…

Storms, William W.; Joyner, David M.

1997-01-01

255

The effects of exercise-induced muscle damage on maximal intensity intermittent exercise performance  

Microsoft Academic Search

Exercise-induced muscle damage (EIMD) is a common occurrence following activities with a high eccentric component. Alterations to the torque–velocity relationship following EIMD would appear to have serious implications for athletic performance, particularly as they relate to impairment of maximal intensity exercise. However, this has been studied infrequently. The purpose of this study was to assess the effects of EIMD on

Craig Twist; Roger Eston

2005-01-01

256

A review of the pathophysiology of exercise-induced pulmonary haemorrhage in the equine athlete  

Microsoft Academic Search

In the United States, more than 75% of equine athletes are reported to suffer from exercise-related haemorrhage of the respiratory tract (Voynick and Sweeney, 1986; Sweeney et al., 1990). Fiberoptic endoscopy has traced the source of blood to beyond the bifurcation of the trachea. In 1981, the term exercise-induced pulmonary haemorrhage (EIPH) was introduced (Pascoe et al., 1981). Racehorses of

L. L. Donaldson

1991-01-01

257

Effect of bedding on the incidence of exercise induced pulmonary haemorrhage in racehorses in Hong Kong  

Microsoft Academic Search

An investigation into the incidence of exercise induced pulmonary haemorrhage (EIPH) in thoroughbreds in Hong Kong was carried out between the 1981 and 1983 racing seasons. A total of 1039 post race endoscopic examinations were performed in 1982-1983 and the results indicated that 46.8 per cent of runners had EIPH. This was not statistically different from the percentage of horses

DK Mason; EA Collins; KL Watkins

1984-01-01

258

Mechanisms of exercise-induced pulmonary hemorrhage in the equine athlete.  

PubMed

This article discusses exercise-induced pulmonary hemorrhage (EIPH), a pathophysiological syndrome which occurs worldwide in the equine athlete. It reviews the history of EIPH, the incidence in performance horses, the etiology, studies performed on the treadmill to determine the mechanisms of EIPH, and the most likely causes of stress failure of the pulmonary capillaries. PMID:7948646

Erickson, H H; Lowe, B S

1994-01-01

259

Exercise-induced hypoxaemia in master athletes: effects of a polyunsaturated fatty acid diet  

Microsoft Academic Search

Exercise-induced hypoxaemia (EIH) has been associated with an oxygen diffusion limitation. Because polyunsaturated fatty acids (PUFA) administration can modify cell membrane fluidity, we hypothesized that the importance of EIH could be reduced after a 6-week PUFA diet. Resting pulmonary functions and a maximal cycling test were performed before and after the diet, in eight master athletes [48 (SD 6 years)].

B. Aguilaniu; P. Flore; H. Perrault; J. E. Page; E. Payan; J.-R. Lacour

1995-01-01

260

Enhanced vagal modulation and exercise induced ischaemia of the inferoposterior myocardium  

Microsoft Academic Search

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

T Kawasaki; A Azuma; T Kuribayashi; T Taniguchi; S Asada; T Kamitani; S Kawasaki; H Matsubara; H Sugihara

2006-01-01

261

TMEM70 mutations cause isolated ATP synthase deficiency and neonatal mitochondrial encephalocardiomyopathy.  

PubMed

We carried out whole-genome homozygosity mapping, gene expression analysis and DNA sequencing in individuals with isolated mitochondrial ATP synthase deficiency and identified disease-causing mutations in TMEM70. Complementation of the cell lines of these individuals with wild-type TMEM70 restored biogenesis and metabolic function of the enzyme complex. Our results show that TMEM70 is involved in mitochondrial ATP synthase biogenesis in higher eukaryotes. PMID:18953340

Cízková, Alena; Stránecký, Viktor; Mayr, Johannes A; Tesarová, Markéta; Havlícková, Vendula; Paul, Jan; Ivánek, Robert; Kuss, Andreas W; Hansíková, Hana; Kaplanová, Vilma; Vrbacký, Marek; Hartmannová, Hana; Nosková, Lenka; Honzík, Tomás; Drahota, Zdenek; Magner, Martin; Hejzlarová, Katerina; Sperl, Wolfgang; Zeman, Jirí; Houstek, Josef; Kmoch, Stanislav

2008-11-01

262

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

2013-11-01

263

Plant Peroxisomes: Biogenesis and Function  

PubMed Central

Peroxisomes are eukaryotic organelles that are highly dynamic both in morphology and metabolism. Plant peroxisomes are involved in numerous processes, including primary and secondary metabolism, development, and responses to abiotic and biotic stresses. Considerable progress has been made in the identification of factors involved in peroxisomal biogenesis, revealing mechanisms that are both shared with and diverged from non-plant systems. Furthermore, recent advances have begun to reveal an unexpectedly large plant peroxisomal proteome and have increased our understanding of metabolic pathways in peroxisomes. Coordination of the biosynthesis, import, biochemical activity, and degradation of peroxisomal proteins allows for highly dynamic responses of peroxisomal metabolism to meet the needs of a plant. Knowledge gained from plant peroxisomal research will be instrumental to fully understanding the organelle’s dynamic behavior and defining peroxisomal metabolic networks, thus allowing the development of molecular strategies for rational engineering of plant metabolism, biomass production, stress tolerance, and pathogen defense. PMID:22669882

Hu, Jianping; Baker, Alison; Bartel, Bonnie; Linka, Nicole; Mullen, Robert T.; Reumann, Sigrun; Zolman, Bethany K.

2012-01-01

264

Phosphatidylserine Decarboxylase 1 (Psd1) Promotes Mitochondrial Fusion by Regulating the Biophysical Properties of the Mitochondrial Membrane and Alternative Topogenesis of Mitochondrial Genome Maintenance Protein 1 (Mgm1)*  

PubMed Central

Non–bilayer-forming lipids such as cardiolipin, phosphatidic acid, and phosphatidylethanolamine (PE) are proposed to generate negative membrane curvature, promoting membrane fusion. However, the mechanism by which lipids regulate mitochondrial fusion remains poorly understood. Here, we show that mitochondrial-localized Psd1, the key yeast enzyme that synthesizes PE, is required for proper mitochondrial morphology and fusion. Yeast cells lacking Psd1 exhibit fragmented and aggregated mitochondria with impaired mitochondrial fusion during mating. More importantly, we demonstrate that a reduction in PE reduces the rate of lipid mixing during fusion of liposomes with lipid compositions reflecting the mitochondrial membrane. This suggests that the mitochondrial fusion defect in the ?psd1 strain could be due to the altered biophysical properties of the mitochondrial membrane, resulting in reduced fusion kinetics. The ?psd1 strain also has impaired mitochondrial activity such as oxidative phosphorylation and reduced mitochondrial ATP levels which are due to a reduction in mitochondrial PE. The loss of Psd1 also impairs the biogenesis of s-Mgm1, a protein essential for mitochondrial fusion, further exacerbating the mitochondrial fusion defect of the ?psd1 strain. Increasing s-Mgm1 levels in ?psd1 cells markedly reduced mitochondrial aggregation. Our results demonstrate that mitochondrial PE regulates mitochondrial fusion by regulating the biophysical properties of the mitochondrial membrane and by enhancing the biogenesis of s-Mgm1. While several proteins are required to orchestrate the intricate process of membrane fusion, we propose that specific phospholipids of the mitochondrial membrane promote fusion by enhancing lipid mixing kinetics and by regulating the action of profusion proteins. PMID:23045528

Chan, Eliana Y. L.; McQuibban, G. Angus

2012-01-01

265

The Ubiquitin-Proteasome System Regulates Mitochondrial Intermembrane Space Proteins  

PubMed Central

Mitochondrial precursor proteins are synthesized in the cytosol and subsequently imported into mitochondria. The import of mitochondrial intermembrane space proteins is coupled with their oxidative folding and governed by the mitochondrial intermembrane space import and assembly (MIA) pathway. The cytosolic steps that precede mitochondrial import are not well understood. We identified a role for the ubiquitin-proteasome system in the biogenesis of intermembrane space proteins. Interestingly, the function of the ubiquitin-proteasome system is not restricted to conditions of mitochondrial protein import failure. The ubiquitin-proteasome system persistently removes a fraction of intermembrane space proteins under physiological conditions, acting as a negative regulator in the biogenesis of this class of proteins. Thus, the ubiquitin-proteasome system plays an important role in determining the levels of proteins targeted to the intermembrane space of mitochondria. PMID:23508107

Bragoszewski, Piotr; Gornicka, Agnieszka; Sztolsztener, Malgorzata E.

2013-01-01

266

Increased Insulin Sensitivity and Distorted Mitochondrial Adaptations during Muscle Unloading  

PubMed Central

We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics. PMID:23443131

Qi, Zhengtang; Zhang, Yuan; Guo, Wei; Ji, Liu; Ding, Shuzhe

2012-01-01

267

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

268

Valsartan regulates myocardial autophagy and mitochondrial turnover in experimental hypertension.  

PubMed

Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The angiotensin II receptor blocker, valsartan, lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with valsartan (320 mg/d) or conventional triple therapy (reserpine+hydralazine+hydrochlorothiazide) for 4 weeks after 6 weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function, and myocardial oxygenation and microcirculation were assessed by multidetector computer tomography, blood oxygen level-dependent MRI, and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

Zhang, Xin; Li, Zi-Lun; Crane, John A; Jordan, Kyra L; Pawar, Aditya S; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

2014-07-01

269

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. PMID:23983900

Hrelia, Silvana

2013-01-01

270

Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice  

PubMed Central

The present study was designed to determine the effects of Ganoderma lucidum polysaccharides (GL-PS) on exhaustive exercise-induced oxidative stress in skeletal muscle tissues of mice. The mice were divided into four groups (three GL-PS administered groups and the control group). The control group was administered with distilled water and GL-PS administered groups were administered with GL-PS (50, 100 and 200 mg/kg body weight per day). After 28 days, the mice performed an exhaustive swimming exercise, along with the determination of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and malondialdehyde (MDA) levels in the skeletal muscle of mice. The results showed that GL-PS could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of mice. This study provides strong evidence that GL-PS supplementation possessed protective effects against exhaustive exercise-induced oxidative stress. PMID:24600303

Zhonghui, Zhao; Xiaowei, Zheng; Fang, Fang

2013-01-01

271

Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice.  

PubMed

The present study was designed to determine the effects of Ganoderma lucidum polysaccharides (GL-PS) on exhaustive exercise-induced oxidative stress in skeletal muscle tissues of mice. The mice were divided into four groups (three GL-PS administered groups and the control group). The control group was administered with distilled water and GL-PS administered groups were administered with GL-PS (50, 100 and 200 mg/kg body weight per day). After 28 days, the mice performed an exhaustive swimming exercise, along with the determination of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and malondialdehyde (MDA) levels in the skeletal muscle of mice. The results showed that GL-PS could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of mice. This study provides strong evidence that GL-PS supplementation possessed protective effects against exhaustive exercise-induced oxidative stress. PMID:24600303

Zhonghui, Zhao; Xiaowei, Zheng; Fang, Fang

2014-04-01

272

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

273

Protective and biogenesis effects of sodium hydrosulfide on brain mitochondria after cardiac arrest and resuscitation.  

PubMed

Mitochondrial dysfunction plays a critical role in brain injury after cardiac arrest and cardiopulmonary resuscitation (CPR). Recent studies demonstrated that hydrogen sulfide (H2S) donor compounds preserve mitochondrial morphology and function during ischemia-reperfusion injury. In this study, we sought to explore the effects of sodium hydrosulfide (NaHS) on brain mitochondria 24h after cardiac arrest and resuscitation. Male Sprague-Dawley rats were subjected to 6min cardiac arrest and then resuscitated successfully. Rats received NaHS (0.5mg/kg) or vehicle (0.9% NaCl, 1.67ml/kg) 1min before the start of CPR intravenously, followed by a continuous infusion of NaHS (1.5mg/kg/h) or vehicle (5ml/kg/h) for 3h. Neurological deficit was evaluated 24h after resuscitation and then cortex was collected for assessments. As a result, we found that rats treated with NaHS revealed an improved neurological outcome and cortex mitochondrial morphology 24h after resuscitation. We also observed that NaHS therapy reduced intracellular reactive oxygen species generation and calcium overload, inhibited mitochondrial permeability transition pores, preserved mitochondrial membrane potential, elevated ATP level and ameliorated the cytochrome c abnormal distribution. Further studies indicated that NaHS administration increased mitochondrial biogenesis in cortex at the same time. Our findings suggested that administration of NaHS 1min prior CPR and followed by a continuous infusion ameliorated neurological dysfunction 24h after resuscitation, possibly through mitochondria preservation as well as by promoting mitochondrial biogenesis. PMID:25066114

Pan, Hao; Xie, Xuemeng; Chen, Di; Zhang, Jincheng; Zhou, Yaguang; Yang, Guangtian

2014-10-15

274

Effects of  -AMPK knockout on exercise-induced gene activation in mouse skeletal muscle  

Microsoft Academic Search

We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body ?2- and ?1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmill running (90 min), and in recovery. Running increased ?1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA

S. B. Jorgensen; Jørgen F. P. Wojtaszewski; Benoit Viollet; Fabrizio Andreelli; Jesper B. Birk; Ylva Hellsten; Peter Schjerling; Sophie Vaulont; P. Darrell Neufer; Erik A. Richter; Henriette Pilegaard

2005-01-01

275

Intermittent pneumatic compression effect on eccentric exercise-induced swelling, stiffness, and strength loss  

Microsoft Academic Search

Objective: The purpose was to determine if intermittent pneumatic compression (IPC) affects muscle swelling, stiffness, and strength loss resulting from eccentric exercise-induced injury of the elbow flexors. We hypothesized that the compression would decrease swelling and stiffness. Design: Repeated measures design with a before-after trial comparison within each day. Setting: Conducted at a university Somatic Dysfunction Laboratory. Subjects: Twenty-two college

Gary S. Chleboun; John N. Howell; Heather L. Baker; Tina N. Ballard; Jennifer L. Graham; Holly L. Hallman; Lori E. Perkins; Jonathan H. Schauss; Robert R. Conatser

1995-01-01

276

Exercise-induced immune cell apoptosis: image-based model for morphological assessment  

Microsoft Academic Search

Methods of assessing exercise-induced lymphocyte apoptosis have produced varying results. While morphological methods generally\\u000a yield a significantly greater apoptotic index compared to those employing biochemical markers, benefits and limitations are\\u000a associated with each methodology. Of interest in this report is the limitation of subjectivity associated with the morphological\\u000a technique. To overcome the lack of objectivity associated with the morphological method,

James W. Navalta; Refaat Mohamed; Ayman El-Baz; Brian K. McFarlin; T. Scott Lyons

2010-01-01

277

How accurate is the diagnosis of exercise induced asthma among Vancouver schoolchildren?  

Microsoft Academic Search

Background: Limited access to exercise testing facilities means that the diagnosis of exercise induced asthma (EIA) is mainly based on self-reported respiratory symptoms. This is open to error since the correlation between exercise related symptoms and subsequent exercise testing has been shown to be poor.Aim: To study the accuracy of clinically diagnosed EIA among Vancouver schoolchildren.Methods: Fifty two children referred

M Seear; D Wensley

2005-01-01

278

Effect of lignocaine, sodium cromoglycate, and ipratropium bromide in exercise-induced asthma  

Microsoft Academic Search

Eight patients with exercise-induced asthma participated in a single-blind trial comparing the protective effects of inhaled lignocaine (estimated dose 48 mg), sodium cromoglycate (estimated dose 12 mg), and ipratropium bromide (estimated dose 120 ?g). Saline was used as control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) and maximal mid-expiratory flow

WM Tullett; KR Patel; KE Berkin; JW Kerr

1982-01-01

279

Dietary chloride as a possible determinant of the severity of exercise-induced asthma  

Microsoft Academic Search

.   Dietary sodium chloride (NaCl) has been shown to alter the severity of exercise-induced asthma, but it is not known if the\\u000a sodium and chloride ions have independent effects in this regard. The hypothesis tested in the present study was that both\\u000a a low sodium, low chloride diet and a high sodium, low chloride diet would improve post-exercise pulmonary function

T. D. Mickleborough; R. W. Gotshall; E. M. Kluka; C. W. Miller; L Cordain

2001-01-01

280

Dose-response study of sodium cromoglycate in exercise-induced asthma  

Microsoft Academic Search

Ten patients with exercise-induced asthma participated in a single-blind dose-response study comparing the protective effect of inhaled sodium cromoglycate in increasing concentrations from 2 to 40 mg\\/ml. Saline was used as a control. Effects were assessed from the mean maximal percentage fall in forced expiratory volume in one second (FEV1) after the patients had run on a treadmill for eight

K R Patel; K E Berkin; J W Kerr

1982-01-01

281

Controlled-analysis of the effects of inhaled lignocaine in exercise-induced asthma  

Microsoft Academic Search

To determine whether anaesthesia of the intrathoracic airways would attenuate the development of exercise-induced asthma, we studied eight symptomless asthmatic patients by cycle ergometry after saline or lignocaine pretreatment while they were breathing air at 24 degrees C with 9.1 mg of H2O\\/l. Pulmonary mechanics were measured before and after the administration of each agent, and again five minutes after

M P Griffin; E R McFadden; R H Ingram; S Pardee

1982-01-01

282

Relationship of exercise-induced asthma to clinical asthma in childhood  

Microsoft Academic Search

Thirty-three asthmatics were followed up for a mean of 8 1\\/2 years in prospective study in order to observe the clinical course of the disease. The severity of asthma was graded according to the treatment each required to keep him in reasonable health. Regular exercise tests were performed so that a comparison could be made between the degree of exercise-induced

L Balfour-Lynn; M Tooley; S Godfrey

1981-01-01

283

Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma  

Microsoft Academic Search

Treatment of exercise-induced asthma with beclomethasone dipropionate in children with asthma. R. Petersen, L. Agertoft, S. Pedersen. #ERS Journals Ltd 2004. ABSTRACT: A new hydrofluoroalkane-beclomethasone dipropionate (HFA-BDP) aerosol markedly increases drug delivery to the airways. Therefore, even low doses of HFA-BDP should be effective, and the present study assesses this. A randomised, double-blind, crossover study was used to compare the

R. Petersen; L. Agertoft; S. Pedersen

2004-01-01

284

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

285

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

286

The Effects of Creatine Supplementation on Exercise-Induced Muscle Damage  

Microsoft Academic Search

This investigation evaluated the effects of oral creatine (Cr) supplementation on markers of exercise-induced muscle damage following high-force eccentric exercise in subjects randomly administered Cr or placebo (P) in a double-blind fashion. When injected, exogenous phosphocreatine has been shown to stabilize the muscle membrane in cardiac tissue and enhance recovery of strength and power following in- jury. Twenty-three men aged

ERIC S. RAWSON; BRIDGET GUNN; PRISCILLA M. CLARKSON

2001-01-01

287

Leg Immersion in Warm Water, Stretch-Shortening Exercise, and Exercise-Induced Muscle Damage  

PubMed Central

Context: Whether muscle warming protects against exercise-induced muscle damage is unknown. Objective: To determine the effect of leg immersion in warm water before stretch-shortening exercise on the time course of indirect markers of exercise-induced muscle damage. Design: Crossover trial. Setting: Human kinetics laboratory. Patients or Other Participants: Eleven healthy, untrained men (age ?=? 21.5 ± 1.7 years). Intervention(s): Participants' legs were immersed in a water bath at 44 ± 1°C for 45 minutes. Main Outcome Measure(s): Creatine kinase changes in the blood, muscle soreness, prolonged (within 72 hours) impairment in maximal voluntary contraction force and height of drop jump, and electrically evoked muscle force at low and high stimulation frequencies at short and long muscle lengths. Results: Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage, including creatine kinase activity in the blood, muscle soreness, maximal voluntary contraction force, and jump height. The values for maximal voluntary contraction force and jump height, however, were higher during prewarming than for the control condition at 48 hours after stretch-shortening exercise, but this difference was only minor at other time points. Muscle prewarming did not bring about any changes in the dynamics of low-frequency fatigue, registered at either short or long muscle length, within 72 hours of stretch-shortening exercise. Conclusions: Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage. However, the clinical application of muscle prewarming may be limited, because decreasing muscle damage did not necessarily lead to improved voluntary performance. PMID:19030137

Skurvydas, Albertas; Kamandulis, Sigitas; Stanislovaitis, Aleksas; Streckis, Vytautas; Mamkus, Gediminas; Drazdauskas, Adomas

2008-01-01

288

Influence of previous concentric exercise on eccentric exercise-induced muscle damage  

Microsoft Academic Search

This study investigated whether a fatiguing concentric exercise performed immediately before eccentric exercise would exacerbate eccentric exercise-induced muscle damage. One arm of nine female subjects (mean - s: 23.3- 6.7 years) performed 12 maximal eccentric actions of the elbow flexors (ECC), and the other arm performed 100 repetitions of isokinetic concentric actions of the elbow flexors followed by the same

Kazunori Nosaka; Priscilla M. Clarkson

1997-01-01

289

The Effectiveness of Immunotherapy in Treating Exercise-Induced Pulmonary Hemorrhage  

Microsoft Academic Search

Inflammatory airway disease has been linked to exercise-induced pulmonary hemorrhage (EIPH), and consequently, we hypothesized that immunomodulation via concentrated equine serum (CES) treatment would reduce EIPH as evidenced by red blood cell (RBC) concentrations in bronchoalveolar lavage fluid (BALF). Separate trials were conducted on Thoroughbred horses treated with either CES (n=6) or placebo (0.9% saline; n=4). All horses completed pre-treatment

Tammi S. Epp; Paul McDonough; Don E. Myers; Danielle J. Carlin; Brad J. Behnke; Casey A. Kindig; David C. Poole; Howard H. Erickson

2009-01-01

290

Effect of prior high-intensity exercise on exercise- induced arterial hypoxemia in Thoroughbred horses  

Microsoft Academic Search

san. Effect of prior high-intensity exercise on exercise-in- duced arterial hypoxemia in Thoroughbred horses. J Appl Physiol 90: 2371-2377, 2001.—Strenuously exercising horses exhibit arterial hypoxemia and exercise-induced pul- monary hemorrhage (EIPH), the latter resulting from stress failure of pulmonary capillaries. The present study was car- ried out to examine whether the structural changes in the blood-gas barrier caused by a

MURLI MANOHAR; THOMAS E. GOETZ; ASLAM S. HASSAN

291

Etiology of exercise-induced asthma: Physical stress-induced transcription  

Microsoft Academic Search

Exercise-induced asthma (EIA) occurs with a high prevalence in both asthmatic and nonasthmatic individuals. Although understanding\\u000a of the functional genomics (proteomics) in sports medicine remains limited, this review focuses on immunologic changes as\\u000a reflected in transcriptional regulation in respect to EIA. Studies demonstrated that leukotrienes play a significant role\\u000a in EIA. Exercise increases the distribution of leukotrienes and influences the

Thomas Hilberg

2007-01-01

292

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

293

Dietary supplementation of Vitamin E protects heart tissue from exercise-induced oxidant stress  

Microsoft Academic Search

Exhaustive endurance exercise in adult female albino rats (C-Ex) increased the generation of free radicals (R ·) in the myocardium, probably through enhanced oxidative mechanisms. Free radical mediated lipid peroxidation measured in the form of tissue MDA content also increased in C-Ex animals, suggesting the exercise-induced oxidative stress in these animals. Dietary supplementation of Vit E, for a period of

Charles T. Kumar; Veera K. Reddy; M. Prasad; K. Thyagaraju; P. Reddanna

1992-01-01

294

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

295

The Effect of Exhausting Exercise Induced Muscular Fatigue On Functional Stability  

Microsoft Academic Search

Problem statement: To quantify the effect of exhausting exercise induc ed muscular fatigue on functional stability. Approach: About 30 male professional athletes with mean age 23±2.1 years old, mean weight 82±1.3 kg and mean height1 81±9.7 cm were selected for participation in this study. In this study Unstable Biodex platform (level 3) us ed for stability evaluation. Balance performance was

Khodadad Letafatkar; Mohammad Hossein Alizadeh; Mohammad Reza Kordi

2009-01-01

296

Familial hypercholesterolemia impairs exercise-induced systemic vasodilation due to reduced NO bioavailability  

PubMed Central

Hypercholesterolemia impairs endothelial function [e.g., the nitric oxide (NO)-cyclic GMP-phosphodiesterase 5 (PDE5) pathway], limits shear stress-induced vasodilation, and is therefore expected to reduce exercise-induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise-induced vasodilation, we compared the effects of endothelial NO synthase (eNOS) and PDE5 inhibition in chronically instrumented Yucatan (Control) and Rapacz familial hypercholesterolemic (FH) swine, at rest and during treadmill exercise. The increases in systemic vascular conductance produced by ATP (relative to nitroprusside) and exercise were blunted in FH compared with Control swine. The vasoconstrictor response to eNOS inhibition, with nitro-l-arginine (NLA), was attenuated in FH compared with Control swine, both at rest and during exercise. Furthermore, whereas the vasodilator response to nitroprusside was enhanced slightly, the vasodilator response to PDE5 inhibition, with EMD360527, was reduced in FH compared with Control swine. Finally, in the pulmonary circulation, FH resulted in attenuated vasodilator responses to ATP, while maintaining the responses to both NLA and EMD360527. In conclusion, hypercholesterolemia reduces exercise-induced vasodilation in the systemic but not the pulmonary circulation. This reduction appears to be the principal result of a decrease in NO bioavailability, which is mitigated by a lower PDE5 activity. PMID:24157527

de Beer, Vincent J.; Merkus, Daphne; Bender, Shawn B.; Tharp, Darla L.; Bowles, Douglas K.; Duncker, Dirk J.

2013-01-01

297

Familial hypercholesterolemia impairs exercise-induced systemic vasodilation due to reduced NO bioavailability.  

PubMed

Hypercholesterolemia impairs endothelial function [e.g., the nitric oxide (NO)-cyclic GMP-phosphodiesterase 5 (PDE5) pathway], limits shear stress-induced vasodilation, and is therefore expected to reduce exercise-induced vasodilation. To assess the actual effects of hypercholesterolemia on endothelial function and exercise-induced vasodilation, we compared the effects of endothelial NO synthase (eNOS) and PDE5 inhibition in chronically instrumented Yucatan (Control) and Rapacz familial hypercholesterolemic (FH) swine, at rest and during treadmill exercise. The increases in systemic vascular conductance produced by ATP (relative to nitroprusside) and exercise were blunted in FH compared with Control swine. The vasoconstrictor response to eNOS inhibition, with nitro-l-arginine (NLA), was attenuated in FH compared with Control swine, both at rest and during exercise. Furthermore, whereas the vasodilator response to nitroprusside was enhanced slightly, the vasodilator response to PDE5 inhibition, with EMD360527, was reduced in FH compared with Control swine. Finally, in the pulmonary circulation, FH resulted in attenuated vasodilator responses to ATP, while maintaining the responses to both NLA and EMD360527. In conclusion, hypercholesterolemia reduces exercise-induced vasodilation in the systemic but not the pulmonary circulation. This reduction appears to be the principal result of a decrease in NO bioavailability, which is mitigated by a lower PDE5 activity. PMID:24157527

de Beer, Vincent J; Merkus, Daphne; Bender, Shawn B; Tharp, Darla L; Bowles, Douglas K; Duncker, Dirk J; Laughlin, M Harold

2013-12-01

298

Mitochondrial dynamics in Parkinson's disease  

PubMed Central

The unique energy demands of neurons require well-orchestrated distribution and maintenance of mitochondria. Thus, dynamic properties of mitochondria, including fission, fusion, trafficking, biogenesis, and degradation, are critical to all cells, but may be particularly important in neurons. Dysfunction in mitochondrial dynamics has been linked to neuropathies and is increasingly being linked to several neurodegenerative diseases, but the evidence is particularly strong, and continuously accumulating, in Parkinson's disease (PD). The unique characteristics of neurons that degenerate in PD may predispose those neuronal populations to susceptibility to alterations in mitochondrial dynamics. In addition, evidence from PD-related toxins supports that mitochondrial fission, fusion, and transport may be involved in pathogenesis. Furthermore, rapidly increasing evidence suggests that two proteins linked to familial forms of the disease, parkin and PINK1, interact in a common pathway to regulate mitochondrial fission/fusion. Parkin may also play a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy. Taken together, the current data suggests that mitochondrial dynamics may play a role in PD pathogenesis, and a better understanding of mitochondrial dynamics within the neuron may lead to future therapeutic treatments for PD, potentially aimed at some of the earliest pathogenic events. PMID:19332061

Van Laar, Victor S.; Berman, Sarah B.

2009-01-01

299

The over-expression of ERbeta modifies estradiol effects on mitochondrial dynamics in breast cancer cell line.  

PubMed

Mitochondrial biogenesis and function are under the control of 17?-estradiol, which acts through two distinct estrogen receptors (alpha or beta), and the estrogen receptors ratio can determine the final effect of 17?-estradiol on mitochondria. Our aim was to study the effects of 17?-estradiol on mitochondrial biogenesis, dynamics and function in breast cancer cell lines with different estrogen receptors ratios. Mitochondrial biogenesis was increased in MDA-MB-231 (with only estrogen receptor beta expression), T47D (normal estrogen receptors ratio) and MCF-7 (highest estrogen receptors ratio) breast cancer cell lines, in response to different mitochondrial and cellular status. In fact, mitochondria of the MDA-MB-231 and T47D cell lines maintained their functionality, although, the MCF-7 cell line did suffer an important decrease in mitochondrial function. Thus, mitochondrial biogenesis increased in MCF-7 with the aim of mitigating these defective mitochondria. In normal conditions, mitophagic processes remove defective mitochondria to refresh the mitochondrial pool. Mitochondrial dynamics were also under control by 17?-estradiol, and showed modifications in the fusion/fission processes and the modulation of mitochondrial removal. In fact, cells with only estrogen receptor beta or with a low estrogen receptors ratio, such as MDA-MB-231 and T47D, showed an increase in fusion processes. However, the MCF-7 cell line, with more estrogen receptor alpha, also showed an increase in fusion processes, even though the fission processes were diminished and led to an accumulation of unfunctional mitochondria. Finally, the importance of estrogen receptor beta in mitochondrial biogenesis, function, as well as in mitochondrial dynamics was examined. Using the T47D-estrogen receptor beta tetracycline-inducible cell line, the results confirmed that when the overexpression of estrogen receptor beta was inhibited, there was an increase in mitochondrial biogenesis, although these mitochondria were less functional, and with fewer fission events, although there was an increase in fusion processes. PMID:23618876

Sastre-Serra, Jorge; Nadal-Serrano, Mercedes; Pons, Daniel Gabriel; Roca, Pilar; Oliver, Jordi

2013-07-01

300

Mitochondrial targeted antioxidant peptide ameliorates hypertensive cardiomyopathy  

PubMed Central

Objectives We investigated the effect of reducing mitochondrial oxidative stress by the mitochondrial-targeted antioxidant peptide SS-31 in hypertensive cardiomyopathy. Background Oxidative stress has been implicated in hypertensive cardiovascular diseases. Mitochondria and NADPH oxidase have been proposed as primary sites of reactive oxygen species (ROS) generation. Methods The mitochondrial targeted antioxidant peptide SS-31 was used to determine the role of mitochondrial oxidative stress in Angiotensin II (Ang)-induced cardiomyopathy, as well as in G?q overexpressing mice with heart failure. Results Angiotensin II induces mitochondrial ROS in neonatal cardiomyocytes, which is prevented by SS-31, but not the non-targeted antioxidant N-acetyl cysteine (NAC). Continuous administration of Ang for 4 weeks in mice significantly increased both systolic and diastolic blood pressure, and this was not affected by SS-31 treatment. Ang was associated with upregulation of NADPH oxidase 4 (NOX4) expression, increased cardiac mitochondrial protein oxidative damage and induced the signaling for mitochondrial biogenesis. Reducing mitochondrial ROS by SS-31 substantially attenuated Ang-induced NOX4 upregulation, mitochondrial oxidative damage, upregulation of mitochondrial biogenesis, phosphorylation of p38 MAP kinase, and prevented apoptosis, concomitant with amelioration of Ang induced cardiac hypertrophy, diastolic dysfunction, and fibrosis, despite the absence of blood pressure lowering effect. NAC did not show any beneficial effect. SS-31 administration for 4 weeks also partially rescued the heart failure phenotype of G?q overexpressing mice. Conclusions Mitochondrial targeted peptide SS-31 ameliorates cardiomyopathy resulting from prolonged Ang stimulation as well as G?q overexpression, suggesting its potential clinical application for target organ protection in hypertensive cardiovascular diseases. PMID:21620606

Dai, Dao-Fu; Chen, Tony; Szeto, Hazel; Nieves-Cintron, Madeline; Kutyavin, Vassily; Santana, Luis F.; Rabinovitch, Peter S.

2013-01-01

301

Comparative efficacy of inhaled furosemide and disodium cromoglycate in the treatment of exercise-induced asthma in children  

Microsoft Academic Search

Background: Inhaled furosemide has been shown, in patients with asthma, to have prophylactic properties similar to those of disodium cromoglycate. Objective: The aim of this study was to evaluate the protective effect of these drugs in the treatment of exercise-induced asthma. Methods: Fifteen children with exercise-induced asthma (mean age, 10.8 years) underwent exercise challenge after a single dose of nebulized

Raul E. Melo; Dirceu Solé; Charles K. Naspitz

1997-01-01

302

Low mitochondrial DNA content associates with familial longevity: the Leiden Longevity Study.  

PubMed

Long-lived individuals delay aging and age-related diseases like diabetes, hypertension, and cardiovascular disease. The exact underlying mechanisms are largely unknown, but enhanced mitochondrial biogenesis and preservation of mitochondrial function have been suggested to explain healthy ageing. We investigated whether individuals belonging to long-lived families have altered mitochondrial DNA (mtDNA) content, as a biomarker of mitochondrial biogenesis and measured expression of genes regulating mitochondrial biogenesis. mtDNA and nuclear DNA (nDNA) levels were measured in blood samples from 2,734 participants from the Leiden Longevity Study: 704 nonagenarian siblings, 1,388 of their middle-aged offspring and 642 controls. We confirmed a negative correlation of mtDNA content in blood with age and a higher content in females. The middle-aged offspring had, on average, lower levels of mtDNA than controls and the nonagenarian siblings had an even lower mtDNA content (mtDNA/nDNA ratio?=?0.744?±?0.065, 0.767?±?0.058 and 0.698?±?0.074, respectively; p controls-offspring?=?3.4?×?10(-12), p controls-nonagenarians?=?6.5?×?10(-6)), which was independent of the confounding effects of age and gender. Subsequently, we examined in a subset of the study the expression in blood of two genes regulating mitochondrial biogenesis, YY1 and PGC-1?. We found a positive association of YY1 expression and mtDNA content in controls. The observed absence of such an association in the offspring suggests an altered regulation of mitochondrial biogenesis in the members of long-lived families. In conclusion, in this study, we show that mtDNA content decreases with age and that low mtDNA content is associated with familial longevity. Our data suggest that preservation of mitochondrial function rather than enhancing mitochondrial biogenesis is a characteristic of long-lived families. PMID:24554339

van Leeuwen, N; Beekman, M; Deelen, J; van den Akker, E B; de Craen, A J M; Slagboom, P E; 't Hart, L M

2014-06-01

303

Chaperone-protease networks in mitochondrial protein homeostasis.  

PubMed

As essential organelles, mitochondria are intimately integrated into the metabolism of a eukaryotic cell. The maintenance of the functional integrity of the mitochondrial proteome, also termed protein homeostasis, is facing many challenges both under normal and pathological conditions. First, since mitochondria are derived from bacterial ancestor cells, the proteins in this endosymbiotic organelle have a mixed origin. Only a few proteins are encoded on the mitochondrial genome, most genes for mitochondrial proteins reside in the nuclear genome of the host cell. This distribution requires a complex biogenesis of mitochondrial proteins, which are mostly synthesized in the cytosol and need to be imported into the organelle. Mitochondrial protein biogenesis usually therefore comprises complex folding and assembly processes to reach an enzymatically active state. In addition, specific protein quality control (PQC) processes avoid an accumulation of damaged or surplus polypeptides. Mitochondrial protein homeostasis is based on endogenous enzymatic components comprising a diverse set of chaperones and proteases that form an interconnected functional network. This review describes the different types of mitochondrial proteins with chaperone functions and covers the current knowledge of their roles in protein biogenesis, folding, proteolytic removal and prevention of aggregation, the principal reactions of protein homeostasis. This article is part of a Special Issue entitled: Protein Import and Quality Control in Mitochondria and Plastids. PMID:22705353

Voos, Wolfgang

2013-02-01

304

PGC-1?, Mitochondrial Dysfunction and Huntington's Disease  

PubMed Central

The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington’s disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-? coactivator-1? (PGC-1?), a transcriptional master co-regulator of mitochondrial biogenesis, metabolism and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1? in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD. PMID:23602910

Johri, Ashu; Chandra, Abhishek; Beal, M. Flint

2013-01-01

305

Formoterol restores mitochondrial and renal function after ischemia-reperfusion injury.  

PubMed

Mitochondrial biogenesis may be an adaptive response necessary for meeting the increased metabolic and energy demands during organ recovery after acute injury, and renal mitochondrial dysfunction has been implicated in the pathogenesis of AKI. We proposed that stimulation of mitochondrial biogenesis 24 hours after ischemia/reperfusion (I/R)-induced AKI, when renal dysfunction is maximal, would accelerate recovery of mitochondrial and renal function in mice. We recently showed that formoterol, a potent, highly specific, and long-acting ?2-adrenergic agonist, induces renal mitochondrial biogenesis in naive mice. Animals were subjected to sham or I/R-induced AKI, followed by once-daily intraperitoneal injection with vehicle or formoterol beginning 24 hours after surgery and continuing through 144 hours after surgery. Treatment with formoterol restored renal function, rescued renal tubules from injury, and diminished necrosis after I/R-induced AKI. Concomitantly, formoterol stimulated mitochondrial biogenesis and restored the expression and function of mitochondrial proteins. Taken together, these results provide proof of principle that a novel drug therapy to treat AKI, and potentially other acute organ failures, works by restoring mitochondrial function and accelerating the recovery of renal function after injury has occurred. PMID:24511124

Jesinkey, Sean R; Funk, Jason A; Stallons, L Jay; Wills, Lauren P; Megyesi, Judit K; Beeson, Craig C; Schnellmann, Rick G

2014-06-01

306

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

307

The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes  

PubMed Central

Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations. PMID:24639874

2014-01-01

308

Regulation of microRNA biogenesis.  

PubMed

MicroRNAs (miRNAs) are small non-coding RNAs that function as guide molecules in RNA silencing. Targeting most protein-coding transcripts, miRNAs are involved in nearly all developmental and pathological processes in animals. The biogenesis of miRNAs is under tight temporal and spatial control, and their dysregulation is associated with many human diseases, particularly cancer. In animals, miRNAs are ?22 nucleotides in length, and they are produced by two RNase III proteins--Drosha and Dicer. miRNA biogenesis is regulated at multiple levels, including at the level of miRNA transcription; its processing by Drosha and Dicer in the nucleus and cytoplasm, respectively; its modification by RNA editing, RNA methylation, uridylation and adenylation; Argonaute loading; and RNA decay. Non-canonical pathways for miRNA biogenesis, including those that are independent of Drosha or Dicer, are also emerging. PMID:25027649

Ha, Minju; Kim, V Narry

2014-08-01

309

A gene involved in the biogenesis of cytochromes is co-transcribed with a ribosomal protein gene in wheat mitochondria  

Microsoft Academic Search

Sequence analysis of a transcribed region of the wheat mitochondrial (mt) genome revealed two open reading frames (orfs) coding for proteins of 589 and 174 amino acids. Both genes are co-transcribed in a 2.6-kb RNA. The largest orf codes for a hydrophobic protein which bears similarity to a bacterial protein involved in the biogenesis of c-type cytochromes. Its corresponding RNA

Daniel H. Gonzalez; Géraldine Bonnard; Jean-Michel Grienenberger

1993-01-01

310

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

Microsoft Academic Search

Background  Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision\\u000a of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced\\u000a energy deficit effects on glucose metabolism are mitigated by increased dietary protein.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Nineteen men ([mean ± SD] 23 ± 2 y, VO2peak 59 ± 5

Tracey J Smith; Jean-Marc Schwarz; Scott J Montain; Jennifer Rood; Matthew A Pikosky; Carmen Castaneda-Sceppa; Ellen Glickman; Andrew J Young

2011-01-01

311

Pediatric exercise-induced bronchoconstriction: contemporary developments in epidemiology, pathogenesis, presentation, diagnosis, and therapy.  

PubMed

Exercise-induced bronchoconstriction is transient narrowing of the airways following strenuous exercise. It is the earliest sign of asthma and the last to resolve. EIB is found in 90 % of asthmatics and reflects underlying control of asthma. This review is focused on the contemporary developments in pediatric EIB: the epidemiology, pathogenesis, presentation, diagnosis and management. Proper diagnosis by objective pulmonary function and/or exercise challenge and therapy should allow the pediatric asthmatic to enjoy a healthy lifestyle including participation in the chosen sport. PMID:23925985

Randolph, Christopher

2013-12-01

312

Effect of Antioxidant Supplementation on Exercise-Induced Cardiac Troponin Release in Cyclists: A Randomized Trial  

PubMed Central

Background Cardiac troponin is the biochemical gold standard to diagnose acute myocardial infarction. Interestingly however, elevated cardiac troponin concentrations are also frequently observed during and after endurance-type exercise. Oxidative stress associated with prolonged exercise has been proposed to contribute to cardiac troponin release. Therefore, the aim of this study was to assess the effect of 4 week astaxanthin supplementation (a potent cartenoid antioxidant) on antioxidant capacity and exercise-induced cardiac troponin release in cyclists. Methods Thirty-two well-trained male cyclists (age 25±5, weight 73±7 kg, maximum O2 uptake 60±5 mL·kg?1·min?1, Wmax 5.4±0.5 W·kg?1; mean ± SD) were repeatedly subjected to a laboratory based standardized exercise protocol before and after 4 weeks of astaxanthin (20 mg/day), or placebo supplementation in a double-blind randomized manner. Blood samples were obtained at baseline, at 60 min of cycling and immediately post-exercise (? 120 min). Results The pre-supplementation cycling trial induced a significant rise of median cardiac troponin T concentrations from 3.2 (IQR 3.0–4.2) to 4.7 ng/L (IQR 3.7–6.7), immediately post-exercise (p<0.001). Four weeks of astaxanthin supplementation significantly increased mean basal plasma astaxanthin concentrations from non-detectable values to 175±86 µg·kg?1. However, daily astaxanthin supplementation had no effect on exercise-induced cardiac troponin T release (p?=?0.24), as measured by the incremental area under the curve. Furthermore, the elevation in basal plasma astaxanthin concentrations was not reflected in changes in antioxidant capacity markers (trolox equivalent antioxidant capacity, uric acid, and malondialdehyde). Markers of inflammation (high-sensitivity C-reactive protein) and exercise-induced skeletal muscle damage (creatine kinase) were equally unaffected by astaxanthin supplementation. Conclusion Despite substantial increases in plasma astaxanthin concentrations, astaxanthin supplementation did not improve antioxidant capacity in well-trained cyclists. Accordingly, exercise-induced cardiac troponin T concentrations were not affected by astaxanthin supplementation. Trial registration ClinicalTrials.gov NCT01241877 PMID:24260184

Haenen, Guido R.; Bast, Aalt; van Loon, Luc J. C.; van Dieijen-Visser, Marja P.; Meex, Steven J.R.

2013-01-01

313

Identification of Three Exercise-induced Mortality Risk Factors in Patients with COPD.  

PubMed

Abstract The survival rate of chronic obstructive pulmonary disease (COPD) patients with severely reduced exercise capacity is extremely low. We recently identified three life-threatening pathophysiological conditions during cardiopulmonary exercise testing (CPET): (1) exercise-induced hypoxemia, (2) sympathetic overactivity, and (3) progressive respiratory acidosis at low-intensity exercise. The present prospective observation study aimed to determine whether these parameters constitute risk factors of mortality in moderate-to-very severe COPD. Ninety-six COPD patients were followed-up, monthly, for >3 years. Subsequently, spirometry and CPET were performed to examine parameters of exercise-induced hypoxemia ([PaO2 slope, mmHg/L · min(-1)] = Decrease in PaO2/?V? O2 (Difference in ?V? O2 between at rest and at peak exercise)), progression of acidosis ([?pH/?V? O2,/L · min(-1)] = Decrease in pH/?V? O2), and sympathetic overactivity ([?norepinephrine (NE)/?V? O2, ng/mL/L · min(-1)] = Increase in NE/?V? O2). Univariate analysis revealed a significant association between the three conditions with increased mortality. Kaplan-Meier analysis showed that the quartile combining the steepest PaO2 slope (?-55 mmHg/?V? O2 [L/min]), steepest decrease in arterial blood pH (? -1.72/?V? O2 [L/min]), and most rapid increase in plasma NE level (? 5.2 ng/VO2 [L/min]) during incremental exercise was associated with higher all-cause mortality. These conditions showed cumulative effects on COPD patients' survival. Multivariate analyses revealed that these three life-threatening factors are also independent predictors of mortality based on age, heart rate and PaO2 at rest, body mass index, and forced expiratory volume in 1 s. Thus, these new exercise-induced mortality risk factors may lead to more efficient pulmonary rehabilitation programs for COPD patients based on patient-specific exercise-induced pathophysiological profiles. PMID:24914923

Yoshimura, Kenji; Maekura, Ryoji; Hiraga, Toru; Miki, Keisuke; Kitada, Seigo; Miki, Mari; Tateishi, Yoshitaka; Mori, Masahide

2014-12-01

314

Effects of eccentric exercise-induced muscle damage on intramyocellular lipid concentration and high energy phosphates  

Microsoft Academic Search

Eccentric exercise is known to cause changes to the ultrastructure of skeletal muscle and, in turn, may alter the ability\\u000a of the muscle to store and utilise intracellular substrates such as intramyocellular lipid (IMCL). The purpose of this study\\u000a was to test the hypothesis that exercise-induced muscle damage (EIMD) results in IMCL accumulation. Six males (31 ± 6 years;\\u000a mean ± SD, and 72.3 ± 9.7 kg body

Jonathan D. Hughes; Nathan A. Johnson; Stephen J. Brown; Toos Sachinwalla; David W. Walton; Stephen R. Stannard

2010-01-01

315

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

316

Association between circulating angiotensin-converting enzyme and exercise-induced pulmonary haemorrhage in Thoroughbred racehorses.  

PubMed

Exercise-induced pulmonary haemorrhage has an impact on racehorse performance. Although endoscopic diagnosis (with or without the aid of bronchoalveolar lavage) is considered to be the standard diagnostic method for this condition, the use of biomarkers that could aid in quantifying risk and severity of the condition would represent an advance in equine sport medicine. This preliminary research investigated the use of angiotensin-converting enzyme (ACE) activity in plasma of racehorses and demonstrated that ACE activity is increased in horses with higher degrees of haemorrhage and is a promising biomarker for EIPH in racehorses. PMID:22196974

Costa, M F M; Ronchi, F A; Ivanow, A; Carmona, A K; Casarini, D; Slocombe, R F

2012-10-01

317

Exercise-induced pulmonary hemorrhage in horses: the role of pulmonary veins.  

PubMed

While airway endoscopy and bronchoalveolar lavage are the methodsof choice for diagnosing exercise-induced pulmonary hemorrhage (EIPH), these techniques do not allow accurate evaluation of the severity of bleeding. EIPH pathology is characterized by occlusive remodeling of pulmonary veins. Affected veins have large collagen deposits in their walls, which reduces their lumens. In the caudodorsal regions, pulmonary vein wall remodeling is associated with hemosiderin accumulation, bronchial circulation angiogenesis, and fibrosis of the alveolar interstitium, bronchovascular bundle, septa, and pleura. During exercise, venous occlusion increases regional pulmonary capillary pressure, likely causing capillary rupture and resulting in bleeding. PMID:21870340

Derksen, Frederik; Williams, Kurt; Stack, Alice

2011-04-01

318

Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function  

PubMed Central

The positive role of PARP1 in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of PARP1 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of PARP1 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of PARP1. Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Pol?), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in PARP1-depleted cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:25378300

Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor; Mitra, Sankar; Szabo, Csaba

2014-01-01

319

Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function.  

PubMed

The positive role of PARP1 in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of PARP1 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of PARP1 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of PARP1. Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Pol?), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in PARP1-depleted cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:25378300

Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor; Mitra, Sankar; Szabo, Csaba

2014-12-01

320

Mitochondrial Dysfunction: Different Routes to Alzheimer's Disease Therapy  

PubMed Central

Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid ? peptide (A?), an important component in Alzheimer's disease (AD) pathogenesis, and A? can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of A?. In particular we review data concerning A? import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed. PMID:25221640

Picone, Pasquale; Nuzzo, Domenico; Caruana, Luca; Scafidi, Valeria; Di Carlo, Marta

2014-01-01

321

Caloric Restriction and the Nutrient-Sensing PGC-1? in Mitochondrial Homeostasis: New Perspectives in Neurodegeneration  

PubMed Central

Mitochondrial activity progressively declines during ageing and in many neurodegenerative diseases. Caloric restriction (CR) has been suggested as a dietary intervention that is able to postpone the detrimental aspects of aging as it ameliorates mitochondrial performance. This effect is partially due to increased mitochondrial biogenesis. The nutrient-sensing PGC-1? is a transcriptional coactivator that promotes the expression of mitochondrial genes and is induced by CR. It is believed that many of the mitochondrial and metabolic benefits of CR are due to increased PGC-1? activity. The increase of PGC-1? is also positively linked to neuroprotection and its decrement has been involved in the pathogenesis of many neurodegenerative diseases. This paper aims to summarize the current knowledge about the role of PGC-1? in neuronal homeostasis and the beneficial effects of CR on mitochondrial biogenesis and function. We also discuss how PGC-1?-governed pathways could be used as target for nutritional intervention to prevent neurodegeneration. PMID:22829833

Lettieri Barbato, Daniele; Baldelli, Sara; Pagliei, Beatrice; Aquilano, Katia; Ciriolo, Maria Rosa

2012-01-01

322

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

323

Sex Differences in Exercise-Induced Muscle Pain and Muscle Damage  

PubMed Central

There is uncertainty about sex differences in exercise-induced muscle pain and muscle damage due to several methodological weaknesses in the literature. This investigation tested the hypothesis that higher levels of exercise-induced muscle pain and muscle damage indicators would be found in women than men when several methodological improvements were executed in the same study. Participants (N = 33; 42% women) with an average age of 23 years (SD = 2.82) consented to participate. After a familiarization session, participants visited the laboratory before and across four days after eccentric exercise was completed to induce arm muscle pain and muscle damage. Our primary outcomes were arm pain ratings and pressure pain thresholds. However, we also measured the following indicators of muscle damage: arm girth; resting elbow extension; isometric elbow flexor strength; myoglobin (Mb); tumor necrosis factor (TNFa); interleukin 1beta (IL1b); and total nitric oxide (NO). Temporary induction of muscle damage was indicated by changes in all outcome measures except TNFa, and IL1b. In contrast to our hypotheses, women reported moderately lower and less frequent muscle pain than men. Also, women’s arm girth and Mb levels increased moderately less than men’s, but the differences were not significant. Few large sex differences were detected. PMID:23182229

Dannecker, Erin A.; Liu, Ying; Rector, R. Scott; Thomas, Tom R.; Fillingim, Roger B.; Robinson, Michael E.

2012-01-01

324

Proposed new mechanism for food and exercise induced anaphylaxis based on case studies  

PubMed Central

We present two cases of food and exercise-induced anaphylaxis (FEIA) in patients with a diagnosis of oral allergy syndrome (OAS) to the implicated foods. Patient A had FEIA attributed to fresh coriander and tomato and Patient B to fresh celery. These food allergens have been implicated in OAS and have structural antigenic similarity to that of birch and/or grass. Both patients’ allergies were confirmed by fresh skin prick tests. In both cases, strenuous exercise was antecedent to the systemic anaphylaxis reaction and subsequent ingestion without exercise produced only local symptoms of perioral pruritus. We review the current proposed mechanisms for food and exercise induced anaphylaxis to oral allergens and propose a novel and more biologically plausible mechanism. We hypothesize that the inhibitory effects of exercise on gastric acid secretion decreases the digestion of oral allergens and preserves structural integrity, thereby allowing continued systemic absorption of the allergen whether it be profilins, lipid transfer proteins, or other antigenic determinants. PMID:23509907

2013-01-01

325

Sustainability of exercise-induced increases in bone density and skeletal structure  

PubMed Central

Background The prevalence of osteoporosis with related fragility fractures has increased during the last decades. As physical activity influences the skeleton in a beneficial way, exercise may hypothetically be used as a prophylactic tool against osteoporosis. Objective This review evaluates if exercise-induced skeletal benefits achieved during growth remain in a long-term perspective. Design Publications within the field were searched through Medline (PubMed) using the search words: exercise, physical activity, bone mass, bone mineral content (BMC), bone mineral density (BMD) and skeletal structure. We based our inferences on publications with the highest level of evidence, particularly randomised controlled trials (RCT). Results Benefits in BMD achieved by exercise during growth seem to be eroded at retirement, but benefits in skeletal structure may possibly be retained in a longer perspective. Recreational exercise seems to at least partially maintain exercise-induced skeletal benefits achieved during growth. Conclusions Exercise during growth may be followed by long-term beneficial skeletal effects, which could possibly reduce the incidence of fractures. Exercise during adulthood seems to partly preserve these benefits and reduce the age-related bone loss. PMID:19109651

Karlsson, Magnus K.; Nordqvist, Anders; Karlsson, Caroline

2008-01-01

326

Exercise-Induced Norepinephrine Decreases Circulating Hematopoietic Stem and Progenitor Cell Colony-Forming Capacity  

PubMed Central

A recent study showed that ergometry increased circulating hematopoietic stem and progenitor cell (CPC) numbers, but reduced hematopoietic colony forming capacity/functionality under normoxia and normobaric hypoxia. Herein we investigated whether an exercise-induced elevated plasma free/bound norepinephrine (NE) concentration could be responsible for directly influencing CPC functionality. Venous blood was taken from ten healthy male subjects (25.3+/?4.4 yrs) before and 4 times after ergometry under normoxia and normobaric hypoxia (FiO2<0.15). The circulating hematopoietic stem and progenitor cell numbers were correlated with free/bound NE, free/bound epinephrine (EPI), cortisol (Co) and interleukin-6 (IL-6). Additionally, the influence of exercise-induced NE and blood lactate (La) on CPC functionality was analyzed in a randomly selected group of subjects (n?=?6) in vitro under normoxia by secondary colony-forming unit granulocyte macrophage assays. Concentrations of free NE, EPI, Co and IL-6 were significantly increased post-exercise under normoxia/hypoxia. Ergometry-induced free NE concentrations found in vivo showed a significant impairment of CPC functionality in vitro under normoxia. Thus, ergometry-induced free NE was thought to trigger CPC mobilization 10 minutes post-exercise, but as previously shown impairs CPC proliferative capacity/functionality at the same time. The obtained results suggest that an ergometry-induced free NE concentration has a direct negative effect on CPC functionality. Cortisol may further influence CPC dynamics and functionality. PMID:25180783

Mangge, Harald; Pekovits, Karin; Fuchs, Robert; Allard, Nathalie; Schinagl, Lukas; Hofmann, Peter; Dohr, Gottfried; Wallner-Liebmann, Sandra; Domej, Wolfgang; Muller, Wolfram

2014-01-01

327

Action of nedocromil sodium in exercise-induced asthma in adolescents.  

PubMed

In view of the high incidence of exercise-induced asthma (EIA) in asthmatic adolescents and adults, the aim of the present study was to examine the preventive effect of nedocromil sodium administered prior to an exercise provocation test. The study involved 30 adolescents with EIA, aged between 14 and 19 years, who attended gymnastics classes at the Children's Hospital and Aerobics School. Baseline spirometry, six-minute treadmill running and spirometry for 7-15 minutes post-exercise were performed. During the same week and under identical temperature and humidity conditions, the same test was carried out with 4 mg nedocromil sodium (two inhalations) administered 30 minutes before exercise. Original post-exercise FEV1 values were compared with the findings after administration of nedocromil sodium. Seventeen subjects (56%) were totally protected (< 5% decrease in FEV1) and 13 subjects (44%) were partially protected (< 10% decrease in FEV1). EIA persisted in the fifteen subjects who received placebo pretreatment. Nedocromil sodium, administered 30 minutes prior to exercise, was effective, providing an opportunity to enhance the quality of life of the asthmatic patient troubled by exercise-induced symptoms. PMID:8574437

Cavallo, A; Cassaniti, C; Glogger, A; Magrini, H

1995-01-01

328

Epistaxis related to exercise-induced pulmonary haemorrhage in south African Thoroughbreds.  

PubMed

This study investigated if environmental factors had an effect on the incidence of epistaxis related to exercise-induced pulmonary haemorrhage (EIPH) among racehorses in southern Africa. Data covering the period 1986-2001 and involving 778 532 race runs were analysed. This included the following information: date of race, age, sex, name of breeder, trainer, distance, jockey, state of going, weight carried, racing centre and altitude. Veterinarians employed by the Jockey Club suspended officially entered horses that presented with epistaxis (frank bleeding from the nostrils) after racing. On-course endoscopy is not performed as a standard practice at any southern African racetrack. Epistaxis was identified in 1287 horses (0.165%). More horses presented with EIPH-related epistaxis (a) at sea level, (b) from May to October, (c) when older (> 3 years), (d) after 1995, (e) on Fridays and Sundays, and (f) more in geldings than in mares or entire males. No association could be established between epistaxis and breeder, trainer, distance run, jockey, state of going and weight carried. It is concluded that the frequency of EIPH-related epistaxis is associated with altitude, winter and spring, sex and age. It is suggested that racing at lower altitudes may increase the probability of exercise-induced pulmonary haemorrhage. PMID:15038426

Weideman, H; Schoeman, S J; Jordaan, G F; Kidd, M

2003-12-01

329

The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.  

PubMed

Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB? and CB? cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB? receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB? receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. PMID:24148812

Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

2014-02-01

330

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

PubMed

This study aimed to investigate the efficacy of lower limb compression as a recovery strategy following exercise-induced muscle damage (EIMD). Seventeen female volunteers completed 10 x 10 plyometric drop jumps from a 0.6-m box to induce muscle damage. 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 12 h immediately following damaging exercise. Passive recovery group participants had no intervention. Indirect indices of muscle damage (muscle soreness, creatine kinase activity, knee extensor concentric strength, and vertical jump performance) were assessed prior to and 1, 24, 48, 72, and 96 h following plyometric exercise. Plyometric exercise had a significant effect (p < or = 0.05) on all indices of muscle damage. The compression treatment reduced decrements in countermovement jump performance (passive recovery 88.1 +/- 2.8% vs. treatment 95.2 +/- 2.9% of pre-exercise), squat jump performance (82.3 +/- 1.9% vs. 94.5 +/- 2%), and knee extensor strength loss (81.6 +/- 3% vs. 93 +/- 3.2%), and reduced muscle soreness (4.0 +/- 0.23 vs. 2.4 +/- 0.24), but had no significant effect on creatine kinase activity. The results indicate that compression clothing is an effective recovery strategy following exercise-induced muscle damage. PMID:20376479

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

2010-08-01

331

Effects of ginsenosides-Rb1 on exercise-induced oxidative stress in forced swimming mice  

PubMed Central

Background: The fleshy root of Panax ginseng C.A. Meyer (ginseng) is one of the most well-known and valued herbs in traditional Chinese medicine. Ginsenosides are considered mainly responsible for the pharmacological activities of ginseng. The purpose of this study was to investigate the effects of ginsenoside-Rb1 (G-Rb1) on swimming exercise-induced oxidative stress in male mice. Materials and Methods: A total of 48 animals were randomly divided into four groups, with twelve mice in each group. The first, second and third groups were designed as G-Rb1 treatment groups, got 25, 50 and 100 mg/kg bodyweight of G-Rb1, respectively. The fourth group was designed as the control group, got physiologic saline. The mice were intragastrically administered once daily for 4 weeks. The weight-loaded forced swimming test was conducted on the final day of experimentation. Then the exhaustive swimming time, blood lactate, serum creatine kinase (CK), malondialdehyde (MDA) and antioxidant enzymes in liver of mice were measured. Results: The results showed that G-Rb1 could prolong the exhaustive swimming time and improve exercise endurance capacity of mice, as well as accelerate the clearance of blood lactate and decrease serum CK activities. Meanwhile, G-Rb1 could decrease MDA contents and increase superoxide dismutase, catalase, glutathione peroxidase activities in liver of mice. Conclusions: The study suggested that G-Rb1 possessed protective effects on swimming exercise-induced oxidative stress in mice.

Qi, Bo; Zhang, Lan; Zhang, Zhiqun; Ouyang, Jiangqiong; Huang, Hui

2014-01-01

332

Exercise-induced hypoxaemia in elite endurance athletes. Incidence, causes and impact on VO2max.  

PubMed

Arterial oxygenation is well maintained in healthy untrained or moderately trained individuals during exercise. In contrast, approximately 40 to 50% of healthy elite endurance athletes (cyclists and runners) demonstrate a significant reduction in arterial oxygenation during exercise at work rates approaching VO2max. The mechanism(s) to explain this exercise-induced hypoxaemia (EIH) remain controversial. However, hypoventilation and venoarterial shunt do not appear to be involved. By elimination, this suggests that ventilation-perfusion inequality and/or pulmonary diffusion limitations must contribute to EIH in this population. Theoretical and direct experimental evidence exists to support the notion that both ventilation-perfusion inequality and diffusion disequilibrium contribute to EIH; however, the relative contribution of each factor remains to be determined. In athletes who exhibit a profound EIH, the exercise-induced decline in arterial oxygenation results in a limitation of VO2max. Further, athletes who exhibit EIH at sea level suffer more severe gas exchange impairments during short term exposure to altitude than athletes or nonathletes who do not exhibit EIH at sea level. This finding explains much of the observed variance in the decline in VO2max among individuals during short term altitude or hypoxia exposure. PMID:8356374

Powers, S K; Martin, D; Dodd, S

1993-07-01

333

Two dimensional echocardiographic evaluation of exercise-induced left and right ventricular asynergy: correlation with thallium scanning  

SciTech Connect

Adequate real time two dimensional echocardiograms were prospectively obtained before and immediately after graded treadmill exercise testing in 41 of 48 patients who underwent cardiac catheterization for suspected coronary artery disease. Findings were correlated with thallium perfusion scans performed 5 to 10 minutes and 3 hours after the same exercise test. Exercise-induced wall motion abnormalities were detected in 19 of 23 patients with significant coronary artery disease and no prior myocardial infarction as well as in all 5 patients with known previous infarction. Three patients with coronary artery disease experienced new isolated right ventricular asynergy with exercise that would have been missed if only the left ventricle had been evaluated. Exercise-induced thallium perfusion defects showed good correlation with exercise-induced asynergy as detected with echocardiography. Two dimensional echocardiography performed immediately after treadmill stress testing is a feasible and rewarding technique in the evaluation of patients suspected to have coronary artery disease.

Maurer, G.; Nanda, N.C.

1981-10-01

334

Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs  

PubMed Central

Background Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidism has been shown to correlate with decreased von Willebrand factor antigen and potentially increased bleeding tendency. Whether increased gastro intestinal bleeding risk is exacerbated due to changes in the hemostatic balance is unknown. The aim of this study was to investigate the hemostatic balance in sled dogs before and after exercise and in addition evaluate any correlation to thyroid status. Twenty sled dogs have been assessed in untrained and trained condition and immediately after exercise. The first sample was collected in the autumn following a resting period, and subsequently the dogs were exposed to increased intensity of training. After four months the peak of physical condition was reached and a 68 km long sled pulling exercise was performed. Samples were collected before and immediately after the exercise. Evaluated parameters were: plasma thromboelastographic (TEG) R, SP, ? and MA, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP). Results Exercise induced an overall hypercoagulable state characterized by significant decreases of TEG R and SP and an increase of ?, increased concentrations of plasma vWf and decreased aPTT. In addition, a proinflammatory status was seen by a significant increase of serum CRP concentrations. Thyroid status was confirmed to be hypothyroid as training and exercise induced significant decrease of thyroxin (T4), free thyroxin (fT4) and thyroxin stimulating hormone (TSH) concentrations. Fibrinogen decreased significantly and PT increased. The training-induced changes showed correlation between T4, fT4 and aPTT and correlation between TSH and fibrinogen. Exercise-induced changes showed correlation between T4 and PT. Conclusions Exercise was associated with a hypercoagulable state and an increase of vWf concentration in this group of sled dogs. Decreased thyroid hormone concentrations after training and exercise were confirmed, but were associated with increased and not decreased vWf in this group of sled dogs. PMID:24507241

2014-01-01

335

The effect of exercise-induced hypoxemia on blood redox status in well-trained rowers.  

PubMed

Exercise-induced arterial hypoxemia (EIAH), characterized by decline in arterial oxyhemoglobin saturation (SaO(2)), is a common phenomenon in endurance athletes. Acute intensive exercise is associated with the generation of reactive species that may result in redox status disturbances and oxidation of cell macromolecules. The purpose of the present study was to investigate whether EIAH augments oxidative stress as determined in blood plasma and erythrocytes in well-trained male rowers after a 2,000-m rowing ergometer race. Initially, athletes were assigned into either the normoxemic (n = 9, SaO(2) >92%, [Formula: see text]: 62.0 ± 1.9 ml kg(-1) min(-1)) or hypoxemic (n = 12, SaO(2) <92%, [Formula: see text]: 60.5 ± 2.2 ml kg(-1 )min(-1), mean ± SEM) group, following an incremental [Formula: see text] test on a wind resistance braked rowing ergometer. On a separate day the rowers performed a 2,000-m all-out effort on the same rowing ergometer. Following an overnight fast, blood samples were drawn from an antecubital vein before and immediately after the termination of the 2,000-m all-out effort and analyzed for selective oxidative stress markers. In both the normoxemic (SaO(2): 94.1 ± 0.9%) and hypoxemic (SaO(2): 88.6 ± 2.4%) rowers similar and significant exercise increase in serum thiobarbituric acid-reactive substances, protein carbonyls, catalase and total antioxidant capacity concentration were observed post-2,000 m all-out effort. Exercise significantly increased the oxidized glutathione concentration and decreased the ratio of reduced (GSH)-to-oxidized (GSSG) glutathione in the normoxemic group only, whereas the reduced form of glutathione remained unaffected in either groups. The increased oxidation of GSH to GSSG in erythrocytes of normoxemic individuals suggest that erythrocyte redox status may be affected by the oxygen saturation degree of hemoglobin. Our findings indicate that exercise-induced hypoxemia did not further affect the increased blood oxidative damage of lipids and proteins observed after a 2,000-m rowing ergometer race in highly-trained male rowers. The present data do not support any potential link between exercise-induced hypoxemia, oxidative stress increase and exercise performance. PMID:21947454

Kyparos, Antonios; Riganas, Christos; Nikolaidis, Michalis G; Sampanis, Michalis; Koskolou, Maria D; Grivas, Gerasimos V; Kouretas, Dimitrios; Vrabas, Ioannis S

2012-06-01

336

Overexpression of the catalytic subunit of DNA polymerase ? results in depletion of mitochondrial DNA in Drosophila melanogaster  

Microsoft Academic Search

The mechanisms involved in the regulation of mitochondrial DNA (mtDNA) replication, a process that is crucial for mitochondrial biogenesis, are not well understood. In this study, we evaluate the role of DNA polymerase (pol ), the key enzyme in mtDNA replication, in both Drosophila cell culture and in developing flies. We report that overexpression of the pol catalytic subunit (pol

E. Lefai; M. Calleja; I. Ruiz de Mena; A. T. Lagina III; L. S. Kaguni; R. Garesse

2000-01-01

337

Molecular mechanisms of cytochrome c biogenesis: three distinct systems.  

PubMed

The past 10 years have heralded remarkable progress in the understanding of the biogenesis of c-type cytochromes. The hallmark of c-type cytochrome synthesis is the covalent ligation of haem vinyl groups to two cysteinyl residues of the apocytochrome (at a Cys-Xxx-Yyy-Cys-His signature motif). From genetic, genomic and biochemical studies, it is clear that three distinct systems have evolved in nature to assemble this ancient protein. In this review, common principles of assembly for all systems and the molecular mechanisms predicted for each system are summarized. Prokaryotes, plant mitochondria and chloroplasts use either system I or II, which are each predicted to use dedicated mechanisms for haem delivery, apocytochrome ushering and thioreduction. Accessory proteins of systems I and II co-ordinate the positioning of these two substrates at the membrane surface for covalent ligation. The third system has evolved specifically in mitochondria of fungi, invertebrates and vertebrates. For system III, a pivotal role is played by an enzyme called cytochrome c haem lyase (CCHL) in the mitochondrial intermembrane space. PMID:9720859

Kranz, R; Lill, R; Goldman, B; Bonnard, G; Merchant, S

1998-07-01

338

Analysis of the affect measurement conundrum in exercise psychology: II. A conceptual and methodological critique of the Exercise-induced Feeling inventory  

Microsoft Academic Search

Background and purpose: The measurement of affect in the context of exercise has become a controversial issue. To help elucidate some of the problems, the conceptual and methodological bases of the Exercise-induced Feeling Inventory (Gauvin, L., & Rejeski, W.J. (1993). The Exercise-induced Feeling Inventory: Development and initial validation. Journal of Sport & Exercise Psychology, 15, 403.) are critiqued, emphasizing deviations

Panteleimon Ekkekakis; Steven J. Petruzzello

2001-01-01

339

The Circadian Clock Coordinates Ribosome Biogenesis  

PubMed Central

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frederic

2013-01-01

340

Curli biogenesis: order out of disorder.  

PubMed

Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID:24080089

Evans, Margery L; Chapman, Matthew R

2014-08-01

341

Thromboelastometric Profiles of Horses Affected by Exercise-Induced Pulmonary Hemorrhages  

PubMed Central

Exercise-induced pulmonary hemorrhage (EIPH) commonly occurs in race horses. Thromboelastometry (TEM) investigates the whole hemostatic process by evaluating the viscoelastic properties of the blood clot from its formation to fibrinolysis. The aim of this study was to assess whether horses with EIPH have abnormal thromboelastometric profiles. Intrinsic and extrinsic pathways, fibrinogen activity and fibrinolysis were investigated by TEM before and after the race in negative controls and in horses on which EIPH was confirmed by bronchoscopy. Compared with controls, horses with EIPH had an increased coagulability in both pre- and postrace samplings, especially for the intrinsic pathway and for the fibinrolytic activity. These results suggest that coagulation is preactivated in horses prone to develop EIPH, possibly due to recent or recurrent hemorrhage. PMID:20953331

Giordano, Alessia; Meazza, Cecilia; Salvadori, Marco; Paltrinieri, Saverio

2010-01-01

342

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. PMID:19552796

Cappelli, Katia; Felicetti, Michela; Capomaccio, Stefano; Pieramati, Camillo; Silvestrelli, Maurizio; Verini-Supplizi, Andrea

2009-01-01

343

Research Article Thromboelastometric Profiles of Horses Affected by Exercise-Induced Pulmonary Hemorrhages  

E-print Network

License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Exercise-induced pulmonary hemorrhage (EIPH) commonly occurs in race horses. Thromboelastometry (TEM) investigates the whole hemostatic process by evaluating the viscoelastic properties of the blood clot from its formation to fibrinolysis. The aim of this study was to assess whether horses with EIPH have abnormal thromboelastometric profiles. Intrinsic and extrinsic pathways, fibrinogen activity and fibrinolysis were investigated by TEM before and after the race in negative controls and in horses on which EIPH was confirmed by bronchoscopy. Compared with controls, horses with EIPH had an increased coagulability in both pre- and postrace samplings, especially for the intrinsic pathway and for the fibinrolytic activity. These results suggest that coagulation is preactivated in horses prone to develop EIPH, possibly due to recent or recurrent hemorrhage. 1.

unknown authors

344

Thromboelastometric profiles of horses affected by exercise-induced pulmonary hemorrhages.  

PubMed

Exercise-induced pulmonary hemorrhage (EIPH) commonly occurs in race horses. Thromboelastometry (TEM) investigates the whole hemostatic process by evaluating the viscoelastic properties of the blood clot from its formation to fibrinolysis. The aim of this study was to assess whether horses with EIPH have abnormal thromboelastometric profiles. Intrinsic and extrinsic pathways, fibrinogen activity and fibrinolysis were investigated by TEM before and after the race in negative controls and in horses on which EIPH was confirmed by bronchoscopy. Compared with controls, horses with EIPH had an increased coagulability in both pre- and postrace samplings, especially for the intrinsic pathway and for the fibinrolytic activity. These results suggest that coagulation is preactivated in horses prone to develop EIPH, possibly due to recent or recurrent hemorrhage. PMID:20953331

Giordano, Alessia; Meazza, Cecilia; Salvadori, Marco; Paltrinieri, Saverio

2010-01-01

345

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. PMID:21602910

Foster, Philip P.; Rosenblatt, Kevin P.; Kuljis, Rodrigo O.

2011-01-01

346

Evidence of local exercise-induced systemic oxidative stress in chronic obstructive pulmonary disease patients.  

PubMed

Chronic inactivity may not be the sole factor involved in the myopathy of chronic obstructive pulmonary disease (COPD) patients. One hypothesis is that exercise-induced oxidative stress that leads to muscle alterations may also be involved. This study investigated whether exercise localised to a peripheral muscle group would induce oxidative stress in COPD patients. Eleven COPD patients (FEV1 1.15+/-0.4 L (mean+/-SD)) and 12 healthy age-matched subjects with a similar low quantity of physical activity performed endurance exercise localised to a peripheral muscle group, the quadriceps of the dominant leg. The authors measured plasma levels of thiobarbituric reactive substances (TBARs) as an index of oxidative stress, the release in superoxide anion (O2*-) by stimulated phagocytes as an oxidant, and blood vitamin E as one antioxidant. Quadriceps endurance was significantly lower in the COPD patients compared with healthy subjects (136+/-16 s versus 385+/-69 s (mean+/-SEM), respectively). A significant increase in TBARs 6 h after quadriceps exercise was only found in the COPD patients. In addition, significantly higher O2*- release and lower blood vitamin E levels were found in COPD patients than in controls at rest. This blood vitamin E level was significantly correlated with the resting level of plasma TBARs in the COPD patients. This study mainly showed that quadriceps exercise induced systemic oxidative stress in chronic obstructive pulmonary disease patients and that vitamin E levels were decreased in these patients at rest. The exact relevance of these findings to chronic obstructive pulmonary disease myopathy needs to be elucidated. PMID:12449164

Couillard, A; Koechlin, C; Cristol, J P; Varray, A; Prefaut, C

2002-11-01

347

Frusemide attenuates the exercise-induced rise in pulmonary capillary blood pressure in horses.  

PubMed

Catheter mounted micro-tip-manometers (the signals from which were matched with fluid-filled pressure signals from same cardiovascular sites and zeroed at the point of the shoulder), were used to study pulmonary haemodynamics in 8 healthy sound horses at rest and during exercise performed at 8, 10, 12 and 14 m/s on a treadmill. Measurements were made without frusemide (control) and 4 h after iv administration of 250 mg frusemide. Post-frusemide data were also obtained on a separate day, and these observations were not significantly different from those made on the same day as controls. Pre-frusemide values of heart rate, mean right atrial pressure, mean pulmonary artery pressure, mean pulmonary artery wedge pressure and mean pulmonary capillary pressure at 14 m/s were 214 +/- 5 beats/min, 54 +/- 4, 92 +/- 4, 65 +/- 6 and 79 +/- 5 mmHg, respectively. Exercise at 14 m/s after frusemide resulted in a similar heart rate (216 +/- 4 beats/min), but the mean right atrial, pulmonary arterial, pulmonary artery wedge and pulmonary capillary pressures were all significantly lower, i.e. 34 +/- 5, 79 +/- 4, 45 +/- 4, and 62 +/- 3 mmHg, respectively. Attenuation, by frusemide, of the exercise-induced rise in pulmonary capillary pressure would lower the magnitude of the transmural force exerted on the pulmonary capillaries. If, therefore, exercise-induced pulmonary haemorrhage (EIPH) is caused by stress failure of pulmonary capillaries, frusemide pretreatment has the potential for reducing/limiting the extent of EIPH. PMID:8143666

Manohar, M; Hutchens, E; Coney, E

1994-01-01

348

Pulmonary haemodynamics in the exercising horse and their relationship to exercise-induced pulmonary haemorrhage.  

PubMed

Exercise-induced pulmonary haemorrhage (EIPH) is a common occurrence in race horses. Although blood in cases of EIPH has been suspected to originate from the bronchial circulation, which receives approximately 1% of the left ventricular output, physiological evidence has recently emerged to indicate that the pulmonary circulation, which receives the entire output of the right ventricle, is a more likely source. High transmural pulmonary capillary pressures have been shown to cause breaks in the capillary endothelium, basement membrane as well as in the alveolar epithelium. Blood constituents escape into the interstitium and alveoli through such breaks in the blood-gas barrier--a phenomenon referred to as stress failure of pulmonary capillaries. Concomitant measurement of pulmonary arterial and venous pressures in strenuously exercising horses have revealed that both of these variables increased dramatically such that the intravascular pulmonary capillary pressure during exertion at 14 m/s (heart rate of 214 beats/min) approached 105 cm H2O (79 mmHg). Alveolar pressure during peak inhalation is likely to be negative; therefore, it is probable that transmural (intravascular minus perivascular) pulmonary capillary pressure of maximally exercising horses may be greater than 105 cm of water. Thus, the pulmonary blood-gas barrier, which has to be thin to provide for adequate diffusion of O2, is exposed to very high transmural forces associated with high cardiac output during exercise. Recent evidence suggests that the alveolar-capillary membrane may not be able to withstand the high transmural forces during maximal exertion, and that stress failure of pulmonary capillaries occurs, leading to EIPH. Intravenous furosemide premedication 4 h before exercise attenuates the exercise-induced rise in pulmonary arterial, capillary and venous pressures and, therefore, may be efficacious in reducing or limiting the extent of EIPH in race horses. PMID:8298955

Manohar, M; Hutchens, E; Coney, E

1993-01-01

349

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. PMID:22555867

Finefield, Jennifer M.; Sherman, David H.; Kreitman, Martin; Williams, Robert M.

2012-01-01

350

Leucine modulation of mitochondrial mass and oxygen consumption in skeletal muscle cells and adipocytes  

PubMed Central

Background The effects of dairy on energy metabolism appear to be mediated, in part, by leucine and calcium which regulate both adipocyte and skeletal muscle energy metabolism. We recently demonstrated that leucine and calcitriol regulate fatty acid oxidation in skeletal muscle cells in vitro, with leucine promoting and calcitriol suppressing fatty acid oxidation. Moreover, leucine coordinately regulated adipocyte lipid metabolism to promote flux of lipid to skeletal muscle and regulate metabolic flexibility. We have now investigated the role of mitochondrial biogenesis in mediating these effects. Methods We tested the effect of leucine, calcitriol and calcium in regulation of mitochondrial mass using a fluorescence method and tested mitochondrial biogenesis regulatory genes as well mitochondrial component genes using real-time PCR. We also evaluated the effect of leucine on oxygen consumption with a modified perfusion system. Results Leucine (0.5 mM) increased mitochondrial mass by 30% and 53% in C2C12 myocytes and 3T3-L1 adipocytes, respectively, while calcitriol (10 nM) decreased mitochondrial abundance by 37% and 27% (p < 0.02). Leucine also stimulated mitochondrial biogenesis genes SIRT-1, PGC-1? and NRF-1 as well as mitochondrial component genes UCP3, COX, and NADH expression by 3–5 fold in C2C12 cells (p < 0.003). Adipocyte-conditioned medium reduced mitochondrial abundance (p < 0.001) and decreased UCP3 but increased PGC-1? expression in myocytes, suggesting a feedback stimulation of mitochondrial biogenesis. Similar data were observed in C2C12 myocytes co-cultured with adipocytes, with co-culture markedly suppressing mitochondrial abundance (p < 0.02). Leucine stimulated oxygen consumption in both C2C12 cells and adipocytes compared with either control or valine-treated cells. Transfection of C2C12 myocytes with SIRT-1 siRNA resulted in parallel suppression of SIRT-1 expression and leucine-induced stimulation of PGC-1? and NRF-1, indicating that SIRT-1 mediates leucine induced mitochondrial biogenesis in muscle cells. Conclusion These data suggest that leucine and calcitriol modulation of muscle and adipocyte energy metabolism is mediated, in part, by mitochondrial biogenesis. PMID:19500359

Sun, Xiaocun; Zemel, Michael B

2009-01-01

351

MicroRNA biogenesis: dicing assay.  

PubMed

RNA-induced silencing complex is the cytoplasmic effector machine of the microRNA (miRNA) pathway and contains a single-stranded miRNA guiding it to its target mRNAs. The biogenesis of mature miRNAs is a regulatory process achieved by complex machinery composed of few protein components, among which the ribonuclease III Dicer plays a central role. Dicer is essential for miRNA maturation and catalyzes one of the rate-limiting steps of miRNA production. In this chapter, we describe a protocol to study the catalytic activity of Dicer in cell extracts by measuring their ability to process precursor RNA (pre-miRNAs) into functional mature miRNAs. Impairment of the miRNA biogenesis machinery due to loss-of-function mutations in effectors of the pathway such as Dicer has been demonstrated before. Dicing assay can be used in cancer to assess Dicer enzymatic activity compared with healthy controls. Therefore, this experimental approach is likely to be useful to researchers investigating the main steps of miRNA biogenesis and function in human health and diseases. PMID:25055915

Melo, Carlos A; Melo, Sonia A

2014-01-01

352

Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver?  

PubMed Central

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the US and many western countries. It is well known that APAP induces mitochondrial damage to trigger centrilobular necrosis. Emerging evidence suggests that autophagic removal of damaged mitochondria may protect against APAP-induced liver injury. Electron and confocal microscopy analysis of liver tissues revealed that APAP overdose triggers unique biochemical and pathological zonated changes in the mouse liver, which includes necrosis (zone 1), mitochondrial spheroid formation (zone 2), autophagy (zone 3) and mitochondrial biogenesis (zone 4). In this graphic review, we discuss the role of autophagy/mitophagy in limiting the expansion of necrosis and promoting mitochondrial biogenesis and liver regeneration for the recovery of APAP-induced liver injury. We also discuss possible mechanisms that could be involved in regulating APAP-induced autophagy/mitophagy and the formation of mitochondrial spheroids. PMID:24191236

Ni, Hong-Min; Williams, Jessica A; Jaeschke, Hartmut; Ding, Wen-Xing

2013-01-01

353

Effect of Ambrotose AO® on resting and exercise-induced antioxidant capacity and oxidative stress in healthy adults  

Microsoft Academic Search

BACKGROUND: The purpose of this investigation was to determine the effects of a dietary supplement (Ambrotose AO®) on resting and exercise-induced blood antioxidant capacity and oxidative stress in exercise-trained and untrained men and women. METHODS: 25 individuals (7 trained and 5 untrained men; 7 trained and 6 untrained women) received Ambrotose AO® (4 capsules per day = 2 grams per

Richard J Bloomer; Robert E Canale; Megan M Blankenship; Kelsey H Fisher-Wellman

2010-01-01

354

The role of histamine and noradrenaline in allergic and exercise induced asthma of childhood, and the effect of theophylline treatment  

Microsoft Academic Search

Summary To investigate whether endogenous transmitters play a role in different forms of bronchial asthma we determined histamine and noradrenaline plasma levels as well as airway resistance (Rt) before and after exercise and allergen challenge in children. The study demonstrates that in exercise induced asthma (EIA) broncho-constriction was paralleled by increases of noradrenaline, but not of histamine plasma levels. This

D. Reinhardt; B. Becker; M. Nagel-Hiemke; M. Matern; F. Wegner; F. Fuchs

1982-01-01

355

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

356

The effect of exercise-induced muscle damage on isometric and dynamic knee extensor strength and vertical jump performance  

Microsoft Academic Search

In this study, we assessed the effect of exercise-induced muscle damage on knee extensor muscle strength during isometric, concentric and eccentric actions at 1.57 rad · s -1 and vertical jump performance under conditions of squat jump, countermovement jump and drop jump. The eight participants (5 males, 3 females) were aged 29.5 - 7.1 years (mean - s ). These

Christopher Byrne; Roger Eston

2002-01-01

357

Efficacy of beta-blocker therapy in symptomatic athletes with exercise-induced intra-ventricular gradients  

Microsoft Academic Search

BACKGROUND: Upright exercise stress echocardiography (SE) induces significant intraventricular gradient (IVG) and systolic anterior motion (SAM) in a large proportion of symptomatic athletes, who may therefore benefit from a negative inotropic therapy. The purpose of the present study was to assess the effect of chronic oral ? blocker therapy on the occurrence of exercise-induced IVG and mitral valve SAM, in

Carlos Cotrim; Luís R Lopes; Ana R Almeida; Rita Miranda; Almeida G Ana; Hortense Cotrim; José P Andrade; Eugenio Picano; Manuel Carrageta

2010-01-01

358

Exercise-induced depression of the diaphragm motor evoked potential is not affected by non-invasive ventilation  

Microsoft Academic Search

Whole body exercise is followed by a depression of the diaphragm motor evoked potential (MEP). It is unknown whether the change is due to diaphragm activity or whole body exercise. To test the hypothesis that exercise-induced MEP depression was related to diaphragm activity, we performed two experiments. The first examined the effect of whole body exercise, performed with and without

Mark J. Dayer; Sophie Jonville; Michelle Chatwin; Elisabeth B. Swallow; Raphael Porcher; Tarek Sharshar; Ewen T. Ross; Nicholas S. Hopkinson; John Moxham; Michael I. Polkey

2007-01-01

359

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

EPA Science Inventory

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. O...

360

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

2013-07-01

361

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. PMID:23539539

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

362

Abnormal Synaptic Vesicle Biogenesis in Drosophila Synaptogyrin Mutants  

E-print Network

Sustained neuronal communication relies on the coordinated activity of multiple proteins that regulate synaptic vesicle biogenesis and cycling within the presynaptic terminal. Synaptogyrin and synaptophysin are conserved ...

Stevens, Robin Jean

363

Impaired mitochondrial function in human placenta with increased maternal adiposity.  

PubMed

The placenta plays a key role in regulation of fetal growth and development and in mediating in utero developmental programming. Obesity, which is associated with chronic inflammation and mitochondrial dysfunction in many tissues, exerts a programming effect in pregnancy. We determined the effect of increasing maternal adiposity and of fetal sex on placental ATP generation, mitochondrial biogenesis, expression of electron transport chain subunits, and mitochondrial function in isolated trophoblasts. Placental tissue was collected from women with prepregnancy BMI ranging from 18.5 to 45 following C-section at term with no labor. Increasing maternal adiposity was associated with excessive production of reactive oxygen species and a significant reduction in placental ATP levels in placentae with male and female fetuses. To explore the potential mechanism of placental mitochondrial dysfunction, levels of transcription factors regulating the expression of genes involved in electron transport and mitochondrial biogenesis were measured. Our in vitro studies showed significant reduction in mitochondrial respiration in cultured primary trophoblasts with increasing maternal obesity along with an abnormal metabolic flexibility of these cells. This reduction in placental mitochondrial respiration in pregnancies complicated by maternal obesity could compromise placental function and potentially underlie the increased susceptibility of these pregnancies to fetal demise in late gestation and to developmental programming. PMID:25028397

Mele, James; Muralimanoharan, Sribalasubashini; Maloyan, Alina; Myatt, Leslie

2014-09-01

364

ATP, phosphocreatine and lactate in exercising muscle in mitochondrial disease and McArdle’s disease  

Microsoft Academic Search

We studied exercise-induced changes in the adenosine triphosphate (ATP), phosphocreatine (PCr), and lactate levels in the skeletal muscle of mitochondrial patients and patients with McArdle’s disease. Needle muscle biopsy specimens for biochemical measurement were obtained before and immediately after maximal short-term bicycle exercise test from 12 patients suffering from autosomal dominant and recessive forms of progressive external ophthalmoplegia and multiple

Mervi Löfberg; Harri Lindholm; Hannu Näveri; Anna Majander; Anu Suomalainen; Anders Paetau; Anssi Sovijärvi; Matti Härkönen; Hannu Somer

2001-01-01

365

Biogenesis of mitochondria: dual role of Tom7 in modulating assembly of the preprotein translocase of the outer membrane.  

PubMed

Biogenesis of the translocase of the outer mitochondrial membrane (TOM complex) involves the assembly of the central ?-barrel forming protein Tom40 with six different subunits that are embedded in the membrane via ?-helical transmembrane segments. The sorting and assembly machinery (SAM complex) of the outer membrane plays a central role in this process. The SAM complex mediates the membrane integration of ?-barrel precursor proteins including Tom40. The small Tom proteins Tom5 and Tom6 associate with the precursor of Tom40 at the SAM complex at an early stage of the assembly process and play a stimulatory role in the formation of the mature TOM complex. A fraction of the SAM components interacts with the outer membrane protein mitochondrial distribution and morphology protein 10 (Mdm10) to form the SAM-Mdm10 machinery; however, different views exist on the function of the SAM-Mdm10 complex. We report here that the third small Tom protein, Tom7, plays an inhibitory role at two distinct steps in the biogenesis of the TOM complex. First, Tom7 plays an antagonistic role to Tom5 and Tom6 at the early stage of Tom40 assembly at the SAM complex. Second, Tom7 interacts with Mdm10 that is not bound to the SAM complex, and thus promotes dissociation of the SAM-Mdm10 complex. Since the SAM-Mdm10 complex is required for the biogenesis of Tom22, Tom7 delays the assembly of Tom22 with Tom40 at a late stage of assembly of the TOM complex. Thus, Tom7 modulates the biogenesis of topologically different proteins, the ?-barrel forming protein Tom40 and Tom22 that contains a transmembrane ?-helix. PMID:21059357

Becker, Thomas; Wenz, Lena-Sophie; Thornton, Nicolas; Stroud, David; Meisinger, Chris; Wiedemann, Nils; Pfanner, Nikolaus

2011-01-01

366

Evaluation of serum leaking enzymes and investigation into new biomarkers for exercise-induced muscle damage.  

PubMed

This investigation determined whether existing muscle damage markers and organ damage markers respond to an acute eccentric exercise protocol and are associated with affected muscle symptoms. Nine healthy-young men completed one-leg calf-raise exercise with their right leg on a force plate. They performed 10 sets of 40 repetitions of exercise at 0.5 Hz with a load corresponding to half of their body weight, with 3 min rest between sets. The tenderness of medial gastrocnemius, lateral gastrocnemius and soleus, and the ankle active range of motion (ROM) were assessed before, immediately after, 24 h and 48 h, 72 h, 96 h and 168 h after exercise. Blood and urine were collected pre-exercise and 2 h, 4 h, 24 h, 48 h, 72 h and 96 h post-exercise. Serum was analyzed for creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and aldolase (ALD) activities. We also determined heart-type fatty acid-binding protein (H-FABP), intestinal-type fatty acid-binding protein (I-FABP) and liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-17A, IL-23, nerve growth factor (NGF), soluble-Endothelial (sE)-selectin, s-Leukocyte (L)-selectin, s-Platelets (P)-selectin, and 8-isoprostane in plasma and urine. The tenderness of proximal and middle gastrocnemius increased significantly 72 h (p < 0.05, p < 0.01) after exercise. Ankle active ROM in dorsal flexion decreased significantly 48 h (p < 0.05) and 72 h (p < 0.01) after exercise. CK and ALD activities significantly increased at 72 h (p < 0.05) and remained elevated at 96 h (p < 0.01) postexercise compared to pre-exercise values. Also, ALD which showed relatively lower interindividual variability was significantly correlated with tenderness of middle gastrocnemius at 72 h. LDH activity significantly increased 96 h postexercise (p < 0.01), whereas the increase in AST and ALT activities 96 h post-exercise was not significantly different from pre-exercise values. There were no significant changes in FABPs, NGAL, IL-17A, IL-23, NGF, selectins and 8-isoprostanes in plasma and urine. In conclusion, calf-raise exercise induced severe local muscle damage symptoms which were accompanied by increases in both serum CK and ALD activities, but we could not detect any changes in examined markers of organ damage, inflammation and oxidative stress. Further research is needed to determine other more sensitive biomarkers and the underlying mechanisms of exercise-induced muscle damage. PMID:24974720

Kanda, Kazue; Sugama, Kaoru; Sakuma, Jun; Kawakami, Yasuo; Suzuki, Katsuhiko

2014-01-01

367

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. PMID:21527019

2011-01-01

368

SIGNALING PATHWAYS IN MELANOSOME BIOGENESIS AND PATHOLOGY  

PubMed Central

Melanosomes are the specialized intracellular organelles of pigment cells devoted to the synthesis, storage and transport of melanin pigments, which are responsible for most visible pigmentation in mammals and other vertebrates. As a direct consequence, any genetic mutation resulting in alteration of melanosomal function, either because affecting pigment cell survival, migration and differentiation, or because interfering with melanosome biogenesis, transport and transfer to keratinocytes, is immediately translated into color variations of skin, fur, hair or eyes. Thus, over one hundred genes and proteins have been identified as pigmentary determinants in mammals, providing us with a deep understanding of this biological system, which functions by using mechanisms and processes that have parallels in other tissues and organs. In particular, many genes implicated in melanosome biogenesis have been characterized, so that melanosomes represent an incredible source of information and a model for organelles belonging to the secretory pathway. Furthermore, the function of melanosomes can be associated with common physiological phenotypes, such as variation of pigmentation among individuals, and with rare pathological conditions, such as albinism, characterized by severe visual defects. Among the most relevant mechanisms operating in melanosome biogenesis are the signal transduction pathways mediated by two peculiar G protein-coupled receptors: the melanocortin-1 receptor (MC1R), involved in the fair skin/red hair phenotype and skin cancer; and OA1 (GPR143), whose loss-of-function results in X-linked ocular albinism. This review will focus on the most recent novelties regarding the functioning of these two receptors, by highlighting emerging signaling mechanisms and general implications for cell biology and pathology. PMID:20381640

Schiaffino, Maria Vittoria

2010-01-01

369

BIOGENESIS OF TELOMERASE RNA IN FISSION YEAST  

E-print Network

pathway in S. cerevisiae ........................... 22 Figure 1.6: Telomerase biogenesis pathway in human ..................................... 24 Figure 1.7: Overall structure of the Sm complex in U4 snRNP ......................... 27 Figure 1....8: The Lsm1-7 complex functions in mRNA decapping ...................... 29 Figure 1.9: The Lsm2-8 complex involves U6 snRNP biogeneis ...................... 31 Figure 3.1: The mature 3’ end of TER1 is generated by the first step of splicing...

Tang, Wen

2012-08-31

370

Development of pharmacological strategies for mitochondrial disorders  

PubMed Central

Mitochondrial diseases are an unusually genetically and phenotypically heterogeneous group of disorders, which are extremely challenging to treat. Currently, apart from supportive therapy, there are no effective treatments for the vast majority of mitochondrial diseases. Huge scientific effort, however, is being put into understanding the mechanisms underlying mitochondrial disease pathology and developing potential treatments. To date, a variety of treatments have been evaluated by randomized clinical trials, but unfortunately, none of these has delivered breakthrough results. Increased understanding of mitochondrial pathways and the development of many animal models, some of which are accurate phenocopies of human diseases, are facilitating the discovery and evaluation of novel prospective treatments. Targeting reactive oxygen species has been a treatment of interest for many years; however, only in recent years has it been possible to direct antioxidant delivery specifically into the mitochondria. Increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial membrane lipid milieu have also emerged as possible treatment strategies. Recent technological advances in gene therapy, including allotopic and transkingdom gene expression and mitochondrially targeted transcription activator-like nucleases, have led to promising results in cell and animal models of mitochondrial diseases, but most of these techniques are still far from clinical application. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24116962

Kanabus, M; Heales, S J; Rahman, S

2014-01-01

371

When ribosomes go bad: diseases of ribosome biogenesis  

PubMed Central

Ribosomes are vital for cell growth and survival. Until recently, it was believed that mutations in ribosomes or ribosome biogenesis factors would be lethal, due to the essential nature of these complexes. However, in the last few decades, a number of diseases of ribosome biogenesis have been discovered. It remains a challenge in the field to elucidate the molecular mechanisms underlying them. PMID:20174677

Freed, Emily F.; Bleichert, Franziska; Dutca, Laura M.; Baserga, Susan J.

2010-01-01

372

Acute Exercise Induces FGF21 Expression in Mice and in Healthy Humans  

PubMed Central

Fibroblast growth factor 21 (FGF21) plays an important role in the regulation of energy homeostasis during starvation and has an excellent therapeutic potential for the treatment of type 2 diabetes in rodents and monkeys. Acute exercise affects glucose and lipid metabolism by increasing glucose uptake and lipolysis. However, it is not known whether acute exercise affects FGF21 expression. Here, we showed that serum FGF21 level is increased in mice after a single bout of acute exercise, and that this is accompanied by increased serum levels of free fatty acid, glycerol and ketone body. FGF21 gene expression was induced in the liver but not in skeletal muscle and white adipose tissue of mice after acute exercise, and further, the gene expression levels of hepatic peroxisome proliferator-activated receptor ? (PPAR?) and activating transcription factor 4 (ATF4) were also increased. In addition, we observed increased FGF21 level in serum of healthy male volunteers performing a treadmill run at 50 or 80% VO2max. These results suggest that FGF21 may also be associated with exercise-induced lipolysis in addition to increased catecholamines and reduced insulin. PMID:23667629

Kim, Kook Hwan; Kim, Seong Hun; Min, Young-Ki; Yang, Hun-Mo; Lee, Jeong-Beom; Lee, Myung-Shik

2013-01-01

373

The effects of rehydration on cycling performance after exercise-induced dehydration.  

PubMed

The effects of 7.6% carbohydrate-electrolyte solution (CES) and placebos (P) on rehydration (R) after exercise-induced dehydration and on a subsequent time-trial (TT) of cycling performance were studied. Thirteen male subjects exercised in a thermally-controlled environment (28 degrees C, 63% RH) until 3% of their body weight was lost. After exercise, the subjects moved to a neutral environment (22 degrees C) and rested for 30 minutes prior to a 2-hour R period. During R, subjects were fed CES or P to a maximum volume of 120% of previous body mass loss at 0, 30, and 60 minutes, in bolus-doses of 50%, 40% and 30% respectively. After R, subjects performed a 1-hour TT with no further fluid intake. % R with CES was significantly higher than with P (70 +/- 3% vs 60 +/- 5%; p < 0.01). During the TT, blood glucose dropped in the CES group but not in the P group. It was found that, despite a more effective R with CES, the performance results did not differ between groups (65.1 +/- 2.2 minutes and 65.2 +/- 2.3 minutes for CES and P respectively). It is suggested that an insulin-mediated rebound effect on CHO metabolism during TT, in which no further CHO was supplied, nullified the benefits of rehydration. PMID:12236441

Singh, R; Brouns, F; Kovacs, E

2002-06-01

374

Topical cooling (icing) delays recovery from eccentric exercise-induced muscle damage.  

PubMed

It is generally thought that topical cooling can interfere with blood perfusion and may have positive effects on recovery from a traumatic challenge. This study examined the influence of topical cooling on muscle damage markers and hemodynamic changes during recovery from eccentric exercise. Eleven male subjects (age 20.2 ± 0.3 years) performed 6 sets of elbow extension at 85% maximum voluntary load and randomly assigned to topical cooling or sham groups during recovery in a randomized crossover fashion. Cold packs were applied to exercised muscle for 15 minutes at 0, 3, 24, 48, and 72 hours after exercise. The exercise significantly elevated circulating creatine kinase-MB isoform (CK-MB) and myoglobin levels. Unexpectedly, greater elevations in circulating CK-MB and myoglobin above the control level were noted in the cooling trial during 48-72 hours of the post-exercise recovery period. Subjective fatigue feeling was greater at 72 hours after topical cooling compared with controls. Removal of the cold pack also led to a protracted rebound in muscle hemoglobin concentration compared with controls. Measures of interleukin (IL)-8, IL-10, IL-1?, and muscle strength during recovery were not influenced by cooling. A peak shift in IL-12p70 was noted during recovery with topical cooling. These data suggest that topical cooling, a commonly used clinical intervention, seems to not improve but rather delay recovery from eccentric exercise-induced muscle damage. PMID:22820210

Tseng, Ching-Yu; Lee, Jo-Ping; Tsai, Yung-Shen; Lee, Shin-Da; Kao, Chung-Lan; Liu, Te-Chih; Lai, Cheng- Hsiu; Harris, M Brennan; Kuo, Chia-Hua

2013-05-01

375

Effects of baseline serum levels of Se on markers of eccentric exercise-induced muscle injury.  

PubMed

Inflammation and oxidative stress have been implicated in the mechanism of eccentric exercise-induced muscle injury. This study examined whether baseline serum levels of selenium (Se), a trace element that participates in both antioxidant and anti-inflammatory systems, affects the overall response to injury. Thirteen males performed 36 maximal eccentric actions with the elbow flexors of the non-dominant arm on a motorized dynamometer. Venous blood samples were collected immediately before and after exercise at 2, 24, 48, 72 and 96 hours. Established indicators of muscle damage such as maximum isometric torque (MIT), range of motion (ROM), relaxed arm angle (RANG), flexed arm angle (FANG), arm circumference (CIRC), muscle soreness and serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were determined at the same time points. Baseline serum levels of Se were also measured. Complementary data regarding assessment of Se status were retrieved by the use of a semi-quantitative food frequency questionnaire. All measures changed significantly (p<0.05) after exercise. The main finding of this study was that baseline Se serum levels were associated inversely with CK, LDH and FANG and positively with MIT and ROM (p<0.05). These data suggest that beyond overt Se deficiency, suboptimal Se status possibly worsens muscle functional decrements subsequent to eccentric muscle contractions. PMID:16971747

Milias, G A; Nomikos, T; Fragopoulou, E; Athanasopoulos, S; Antonopoulou, S

2006-01-01

376

The efficacy of ice massage in the treatment of exercise-induced muscle damage.  

PubMed

The purpose of this investigation was to, firstly, examine the effects of repeated applications of ice massage on the indirect markers associated with muscle damage using a within-subjects cross-over design and secondly, to examine how ice massage affects muscle function in both static and dynamic contractions following unaccustomed eccentric exercise. Twelve males performed damaging exercise on two separate occasions. The protocol consisted of three sets of 10 maximal eccentric repetitions of the elbow flexors using isokinetic dynamometry. Subjects were randomly assigned to an ice massage group or placebo group and received treatments immediately post-exercise, 24 and 48 h post-exercise. Muscle function (maximal isometric, slow and fast isokinetic contractions), creatine kinase, myoglobin, muscle soreness, limb girth and range of motion were measured pre, immediately post, 24, 48, 72 and 96 h post-exercise. Significant time effects were observed for all dependent variables (P<0.05). There were no significant differences between treatments. Ice massage is ineffective in reducing the indirect markers associated with exercise-induced muscle damage and enhancing recovery of muscle function in male exercisers unaccustomed to eccentric biased exercise. PMID:16293154

Howatson, G; Gaze, D; van Someren, K A

2005-12-01

377

Assessment of eccentric exercise-induced muscle damage of the elbow flexors by tensiomyography.  

PubMed

Exercise induced muscle damage (EIMD) impairs maximal torque production which can cause a decline in athletic performance and/or mobility. EIMD is commonly assessed by using maximal voluntary contraction (MVC), creatine kinase (CK) and muscle soreness. We propose as an additional technique, tensiomyography (TMG), recently introduced to measure mechanical and muscle contractile characteristics. The purpose of this study was to determine the validity of TMG in detecting changes in maximal torque following EIMD. Nineteen participants performed eccentric elbow flexions to achieve EIMD on the non- dominant arm and used the dominant elbow flexor as a control. TMG parameters, MVC and rate of torque development (RTD) were measured prior to EIMD and repeated for another six consecutive days. Creatine kinase, muscle soreness and limb girth were also measured during this period. Twenty four hours after inducing EIMD, MVC torque, RTD and TMG maximal displacement had significantly (p<0.01) declined by 37%, 44% and 31%, respectively. By day 6 MVC, RTD and TMG recovered to 12%, 24% and 17% of respective pre-EIMD values. In conclusion, as hypothesised TMG maximal displacement significantly followed other standard EIMD responses. This could therefore be useful in detecting muscle damage from impaired muscle function and its recovery following EIMD. PMID:22336641

Hunter, Angus M; Galloway, Stuart D R; Smith, Iain J; Tallent, Jamie; Ditroilo, Massimiliano; Fairweather, Malcolm M; Howatson, Glyn

2012-06-01

378

Astragalus membranaceus improves exercise performance and ameliorates exercise-induced fatigue in trained mice.  

PubMed

Astragalus membranaceus (AM) is a popular "Qi-tonifying" herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training. PMID:24595275

Yeh, Tzu-Shao; Chuang, Hsiao-Li; Huang, Wen-Ching; Chen, Yi-Ming; Huang, Chi-Chang; Hsu, Mei-Chich

2014-01-01

379

Effects of eccentric exercise-induced muscle damage on intramyocellular lipid concentration and high energy phosphates.  

PubMed

Eccentric exercise is known to cause changes to the ultrastructure of skeletal muscle and, in turn, may alter the ability of the muscle to store and utilise intracellular substrates such as intramyocellular lipid (IMCL). The purpose of this study was to test the hypothesis that exercise-induced muscle damage (EIMD) results in IMCL accumulation. Six males (31 ± 6 years; mean ± SD, and 72.3 ± 9.7 kg body mass) performed 300 unilateral, maximal, isokinetic, eccentric contractions (Ecc) (30° s(-1)) of the quadriceps on an isokinetic dynamometer, followed immediately by an equal amount of work by the contralateral leg but with concentric action (Con). Phosphate compounds and IMCL content of the vastus lateralis of both legs were measured using (31)P and (1)H magnetic resonance spectroscopy. IMCL content was higher in Ecc than Con 24 h post but the reverse was evident 48 h post-exercise (P = 0.046). A significant time × trial interaction for resting [P(i)] (P = 0.045), showed increases in Ecc across time but no change in Con. A significant main effect of trial (P = 0.002) was apparent indicating the Ecc leg had marked metabolic dysfunction. The P(i)/PCr ratio showed a significant effect of trial (P = 0.001) with an increase evident in Ecc leg, primarily due to increases in [P(i)]. The present study highlights changes in IMCL content of skeletal muscle following EIMD. PMID:20706732

Hughes, Jonathan D; Johnson, Nathan A; Brown, Stephen J; Sachinwalla, Toos; Walton, David W; Stannard, Stephen R

2010-12-01

380

Improving screening and diagnosis of exercise-induced bronchoconstriction: a call to action.  

PubMed

This article summarizes the findings of an expert panel of nationally recognized allergists and pulmonologists who met to discuss how to improve detection and diagnosis of exercise-induced bronchoconstriction (EIB), a transient airway narrowing that occurs during and most often after exercise in people with and without underlying asthma. EIB is both commonly underdiagnosed and overdiagnosed. EIB underdiagnosis may result in habitual avoidance of sports and physical activity, chronic deconditioning, weight gain, poor asthma control, low self-esteem, and reduced quality of life. Routine use of a reliable and valid self-administered EIB screening questionnaire by professionals best positioned to screen large numbers of people could substantially improve the detection of EIB. The authors conducted a systematic review of the literature that evaluated the accuracy of EIB screening questionnaires that might be adopted for widespread EIB screening in the general population. Results of this review indicated that no existing EIB screening questionnaire had adequate sensitivity and specificity for this purpose. The authors present a call to action to develop a new EIB screening questionnaire, and discuss the rigorous qualitative and quantitative research necessary to develop and validate such an instrument, including key methodological pitfalls that must be avoided. PMID:24811017

Weiler, John M; Hallstrand, Teal S; Parsons, Jonathan P; Randolph, Christopher; Silvers, William S; Storms, William W; Bronstone, Amy

2014-01-01

381

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin  

PubMed Central

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

2014-01-01

382

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.  

PubMed

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

2014-11-01

383

Exercise-induced changes in the lung of Shetland ponies: ultrastructure and morphometry.  

PubMed

The ultrastructural changes in pulmonary alveoli produced by running two ponies on a high speed treadmill at 7.6 m/sec, 3-degree incline, for 2 min support the hypothesis of pulmonary capillary stress failure as an explanation for exercise-induced pulmonary hemorrhage (EIPH). Light microscopy combined with scanning and transmission electron microscopy confirmed the presence of red blood cells and proteinaceous material in the alveolar lumina and interstitial swelling in approximately one third of the pulmonary alveoli examined. Morphometric analysis revealed that the blood-gas barrier was 30-77% thicker on the thin respiratory surface of the interalveolar septa in the cranial lobe of the two exercised ponies, i.e., 0.62 and 0.46 micron, compared to that of the unexercised control pony (0.35 micron). No change in blood-gas barrier thickness was observed in the caudal lobe, although that is where EIPH lesions have been observed in race-horses. Vascular pressures were low (20 mm Hg) in the pulmonary circulation of the Shetland pony at rest but increased more than three fold to 63 mm Hg during exercise. These preliminary morphological and physiological results indicate that a short burst of near-maximal exercise in a non-athletic equine can lead to structural changes in the blood-gas barrier and leakage of blood from pulmonary capillaries despite pulmonary vascular pressures being significantly lower than previously found in the racehorse. PMID:9066143

Erickson, H H; McAvoy, J L; Westfall, J A

1997-01-01

384

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

385

Evaluation of Duovent in the prevention of exercise-induced asthma.  

PubMed

Exercise-induced asthma (EIA) is a frequent symptom in asthmatic patients. The study of drugs which inhibit EIA is very important because EIA seriously limits the life of the patients. In addition, this study could allow further insights to be gained into the pathogenesis of the phenomenon. The aim of the present study is to evaluate the duration of the protective effect of fenoterol alone or in combination with ipratropium bromide administered 5 h before exercise. For this purpose we studied 12 asthmatic patients (7 males and 5 females, mean age 23, range 7-41 years) with EIA, in clinical and functional stable state. Respiratory function parameters were measured before and 5 h after the administration of fenoterol 400 or 200 micrograms, or fenoterol 200 micrograms plus ipratropium bromide 80 micrograms (Duovent), or placebo in randomized order. Then, such parameters were measured at 5, 15, 30, and 60 min after exercise, which consisted of free running up and down the stairs. The results show that, at 5 h after the administration of each drug, the protective action against EIA is only partial. However, the intense bronchodilation afforded by the 'active' drugs, and particularly by 400 micrograms of fenoterol, keeps post-exertional respiratory parameters above the baseline values. PMID:2951802

Sanguinetti, C M; De Luca, S; Gasparini, S; Massei, V

1986-01-01

386

Exercise-Induced Changes in Iron Status and Hepcidin Response in Female Runners  

PubMed Central

Background and Aims Exercise-induced iron deficiency is a common finding in endurance athletes. It has been suggested recently that hepcidin may be an important mediator in this process. Objective To determine hepcidin levels and markers of iron status during long-term exercise training in female runners with depleted and normal iron stores. Methods Fourteen runners were divided into two groups according to iron status. Blood samples were taken during a period of eight weeks at baseline, after training and after ten days’ recovery phase. Results Of 14 runners, 7 were iron deficient at baseline and 10 after training. Hepcidin was lower at recovery compared with baseline (p<0.05). The mean cell haemoglobin content, haemoglobin content per reticulocyte and total iron binding capacity all decreased, whereas soluble transferrin receptor and hypochromic red cells increased after training and recovery (p<0.05 for all). Conclusion The prevalence of depleted iron stores was 71% at the end of the training phase. Hepcidin and iron stores decreased during long-term running training and did not recover after ten days, regardless of baseline iron status. PMID:23472137

Auersperger, Irena; Skof, Branko; Leskosek, Bojan; Knap, Bojan; Jerin, Ales; Lainscak, Mitja

2013-01-01

387

The challenge of asthma in adolescent athletes: exercise induced bronchoconstriction (EIB) with and without known asthma.  

PubMed

Exercise induced bronchconstriction (EIB) is defined as a transient increase in airway resistance reflected as at least a 10% decline in FEV1 following at least 6-8 minutes of strenuous exercise. Up to 90% of asthmatics, 45% of individuals with allergic rhinitis, 50% of Olympic athletes, and 12% of the general population have EIB. EIB in adolescence may be either under- or over-diagnosed because of denial of symptoms or misperception of dyspnea or other respiratory symptoms. Diagnosis cannot always rely on history alone and may require an objective exercise challenge or surrogate measure. Management of EIB may require reduction in the exercise provoking the asthma but it can usually be successfully managed with training and the appropriate use of medications, including inhaled beta-agonists, inhaled steroids, and/or leukotriene antagonists. Nonpharmacologic therapy with face masks, warming up and down, and calisthenics may also be an effective adjunct in reducing medication needs. For most adolescents, proper pharmacotherapy will provide complete control of the airway and a normal healthy lifestyle without exercise restrictions. PMID:20568554

Randolph, Chris

2010-04-01

388

Reducing exercise-induced muscular injury in kendo athletes with supplementation of coenzyme Q10.  

PubMed

Intensive physical exercise may cause muscular injury and increase oxidative stress. The purpose of this study was to examine the effect of an antioxidant, coenzyme Q10 (CoQ10), on muscular injury and oxidative stress during exercise training. Eighteen male students, all elite Japanese kendo athletes, were randomly assigned to either a CoQ10 group (n 10) or a placebo group (n 8) in a double-blind manner. Subjects in the CoQ10 group took 300 mg CoQ10 per d for 20 d, while subjects in the placebo group took the same dosage of a placebo. All subjects practised kendo 5.5 h per d for 6 d during the experimental period. Blood samples were taken 2 weeks before, during (1 d, 3 d, 5 d) and 1 week after the training. Serum creatine kinase (CK) activity and myoglobin (Mb) concentration significantly increased in both groups (at 3 d and 5 d). Serum CK (at 3 d), Mb (at 3 d) and lipid peroxide (at 3 d and 5 d) of the CoQ10 group were lower than those of the placebo group. The leucocyte counts in the placebo group significantly increased (at 3 d) and neutrophils significantly increased in both groups (at 3 d and 5 d). Serum scavenging activity against superoxide anion did not change in either group. These results indicate that CoQ10 supplementation reduced exercise-induced muscular injury in athletes. PMID:18284711

Kon, Michihiro; Tanabe, Kai; Akimoto, Takayuki; Kimura, Fuminori; Tanimura, Yuko; Shimizu, Kazuhiro; Okamoto, Tadashi; Kono, Ichiro

2008-10-01

389

[Clinical courses of 18 cases with food-dependent exercise-induced anaphylaxis].  

PubMed

Eighteen cases (7 males and 11 females) of food-dependent exercise-induced anaphylaxis were observed for several years. The age of the patients at the first visit to our hospital ranged from 9 to 43 years (average 24.3 years). The offending foods were wheat in 9 cases, shrimp in 2 cases, shellfish in 1 case, fish in 1 case, and unknown foods in 5 cases. The inducing exercises were ball play games, running, riding a bicycle, swimming, kendo (Japanese fencing), walking, and so on. We advised these patients to avoid eating offending foods or taking exercises, or to take antiallergic medicine such as DSCG, and repirinast. We observed their clinical courses and laboratory data for 2 to 10 years. Only a few cases relapsed anaphylactoid reactions, but all cases have improved until now. In some cases, IgE RAST scores for wheat decreased. In other cases, the rate of histamine release on anti-IgE stimulation decreased after taking DSCG. PMID:10916885

Kano, H; Juji, F; Shibuya, N; Narita, M; Naritaka, S; Suko, M; Morita, Y; Iwata, T

2000-06-01

390

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

PubMed

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 test to volitional fatigue with percent arterial oxyhemoglobin saturation (%SaO2) measured min-by-min. For the purpose of data analysis subjects were divided into three groups according to their level of physical training: 1) untrained (N = 16), 2) moderately trained (N = 27), and 3) elite highly trained endurance athletes (N = 25). EIH was defined as a %SaO2 of less than or equal to 91% during exercise. EIH did not occur in any of the untrained subjects or the moderately trained subjects. However, EIH occurred in 52% of the highly trained endurance athletes tested and was highly reproducible (r = 0.95; P less than 0.05). These findings further confirm the existence of EIH in healthy highly trained endurance athletes and suggests a rather high incidence of EIH in this healthy population. Hence, it is important that the clinician or physiologist performing exercise testing in elite endurance athletes recognize that EIH can and does occur in the elite endurance athlete in the absence of lung disease. PMID:3220070

Powers, S K; Dodd, S; Lawler, J; Landry, G; Kirtley, M; McKnight, T; Grinton, S

1988-01-01

391

Atomic resolution insights into curli fiber biogenesis.  

PubMed

Bacteria produce functional amyloid fibers called curli in a controlled, noncytotoxic manner. These extracellular fimbriae enable biofilm formation and promote pathogenicity. Understanding curli biogenesis is important for appreciating microbial lifestyles and will offer clues as to how disease-associated human amyloid formation might be ameliorated. Proteins encoded by the curli specific genes (csgA-G) are required for curli production. We have determined the structure of CsgC and derived the first structural model of the outer-membrane subunit translocator CsgG. Unexpectedly, CsgC is related to the N-terminal domain of DsbD, both in structure and oxido-reductase capability. Furthermore, we show that CsgG belongs to the nascent class of helical outer-membrane macromolecular exporters. A cysteine in a CsgG transmembrane helix is a potential target of CsgC, and mutation of this residue influences curli assembly. Our study provides the first high-resolution structural insights into curli biogenesis. PMID:21893289

Taylor, Jonathan D; Zhou, Yizhou; Salgado, Paula S; Patwardhan, Ardan; McGuffie, Matt; Pape, Tillmann; Grabe, Grzegorz; Ashman, Elisabeth; Constable, Sean C; Simpson, Peter J; Lee, Wei-chao; Cota, Ernesto; Chapman, Matthew R; Matthews, Steve J

2011-09-01

392

Poxvirus membrane biogenesis: rupture not disruption  

PubMed Central

Summary Enveloped viruses acquire their membrane from the host by budding at, or wrapping by, cellular membranes. Transmission electron microscopy (TEM) images, however, suggested that the prototype member of the poxviridae, vaccinia virus (VACV), may create its membrane ‘de novo’ with free open ends exposed in the cytosol. Within the frame of the German-wide priority programme we re-addressed the biogenesis and origin of the VACV membrane using electron tomography (ET), cryo-EM and lipid analysis of purified VACV using mass spectrometry (MS). This review discussed how our data led to a model of unconventional membrane biogenesis involving membrane rupture and the generation of a single open membrane from open membrane intermediates. Lipid analyses of purified virus by MS suggest an ER origin with a relatively low cholesterol content compared with whole cells, confirming published data. Unlike previous reports using thin-layer chromatography, no depletion of phosphatidylethanolamine was detected. We did detect, however, an enrichment for phosphatidic acid, diacylglycerol and phosphatidylinositol in the virion. Our data are discussed in the light of other pathogens that may require cellular membrane rupture during their intracellular life cycle. PMID:23168015

Locker, Jacomine Krijnse; Chlanda, Petr; Sachsenheimer, Timo; Brugger, Britta

2014-01-01

393

[Biogenesis of melanosomes - the chessboard of pigmentation].  

PubMed

Melanosomes are lysosome-related organelles in retinal pigment epithelial cells and epidermal melanocytes in which melanin pigments are synthesized and stored. Melanosomes are generated by multistep processes in which an immature unpigmented organelle forms and then subsequently matures. Such maturation requires inter-organellar transport of protein cargos required for pigment synthesis but also recruitment of effector proteins necessary for the correct transport of melanosomes to the cell periphery. Several studies have started to unravel the main pathways and mechanisms exploited by melanosomal proteins involved in melanosome structure and melanin synthesis. A major unexpected finding seen early in melanosome biogenesis showed the similarities between the fibrillar sheets of premelanosomes and amyloid fibrils. Late steps of melanosome formation are dependent on pathways regulated by proteins encoded by genes mutated in genetic diseases such as the Hermansky-Pudlak Syndrom (HPS) and different types of albinism. Altogether the findings from the past recent years have started to unravel how specialized cells integrate unique and ubiquitous molecular mechanisms in subverting the endosomal system to generate cell-type specific structures and their associated functions. Further dissection of the melanosomal system will likely shed light not only on the biogenesis of lysosome-related organelles but also on general aspects of vesicular transport in the endosomal system. PMID:21382323

Delevoye, Cédric; Giordano, Francesca; van Niel, Guillaume; Raposo, Graça

2011-02-01

394

Enhancing lysosome biogenesis attenuates BNIP3-induced cardiomyocyte death  

PubMed Central

Hypoxia-inducible pro-death protein BNIP3 (BCL-2/adenovirus E1B 19-kDa interacting protein 3), provokes mitochondrial permeabilization causing cardiomyocyte death in ischemia-reperfusion injury. Inhibition of autophagy accelerates BNIP3-induced cell death, by preventing removal of damaged mitochondria. We tested the hypothesis that stimulating autophagy will attenuate BNIP3-induced cardiomyocyte death. Neonatal rat cardiac myocytes (NRCMs) were adenovirally transduced with BNIP3 (or LacZ as control; at multiplicity of infection = 100); and autophagy was stimulated with rapamycin (100 nM). Cell death was assessed at 48 h. BNIP3 expression increased autophagosome abundance 8-fold and caused a 3.6-fold increase in cardiomyocyte death as compared with control. Rapamycin treatment of BNIP3-expressing cells led to further increase in autophagosome number without affecting cell death. BNIP3 expression led to accumulation of autophagosome-bound LC3-II and p62, and an increase in autophagosomes, but not autolysosomes (assessed with dual fluorescent mCherry-GFP-LC3 expression). BNIP3, but not the transmembrane deletion variant, interacted with LC3 and colocalized with mitochondria and lysosomes. However, BNIP3 did not target to lysosomes by subcellular fractionation, provoke lysosome permeabilization or alter lysosome pH. Rather, BNIP3-induced autophagy caused a decline in lysosome numbers with decreased expression of the lysosomal protein LAMP-1, indicating lysosome consumption and consequent autophagosome accumulation. Forced expression of transcription factor EB (TFEB) in BNIP3-expressing cells increased lysosome numbers, decreased autophagosomes and increased autolysosomes, prevented p62 accumulation, removed depolarized mitochondria and attenuated BNIP3-induced death. We conclude that BNIP3 expression induced autophagosome accumulation with lysosome consumption in cardiomyocytes. Forced expression of TFEB, a lysosomal biogenesis factor, restored autophagosome processing and attenuated BNIP3-induced cell death. PMID:22302006

Ma, Xiucui; Godar, Rebecca J.; Liu, Haiyan; Diwan, Abhinav

2012-01-01

395

Exercise-induced oxyhaemoglobin desaturation, ventilatory limitation and lung diffusing capacity in women during and after exercise  

Microsoft Academic Search

.   Arterial haemoglobin saturation during exercise in healthy young women [eight subjects mean (SEM) age 20.8 (1.8) years] was\\u000a measured to confirm the theory that young women experience exercise-induced arterial hypoxaemia (EIAH) at a lower relative\\u000a percentage of maximal oxygen uptake (VO2max) than has been documented in their male counterparts. To determine if flow limitation [the percentage of the tidal volume\\u000a (V

Justin Walls; Michael Maskrey; Richard Wood-Baker; Wade Stedman

2002-01-01

396

Effects of eccentric exercise-induced muscle injury on blood levels of platelet activating factor (PAF) and other inflammatory markers  

Microsoft Academic Search

It has been reported that exercise with eccentric contractions can induce damage and inflammation in human muscle tissue,\\u000a the severity of which depends on the duration and the intensity of exercise. Platelet activating factor (PAF) is a potent\\u000a inflammatory mediator implicated in a series of pathophysiological conditions. We sought to investigate the relationship between\\u000a PAF and eccentric exercise induced muscle

George A. Milias; Tzortzis Nomikos; Elizabeth Fragopoulou; Spyridon Athanasopoulos; Smaragdi Antonopoulou

2005-01-01

397

Effect of exercise-induced muscle damage on ventilatory and perceived exertion responses to moderate and severe intensity cycle exercise  

Microsoft Academic Search

This study examined the effect of exercise-induced muscle damage (EIMD) on ventilatory and perceived exertion responses to\\u000a cycle exercise. Ten healthy, physically active men cycled for 6 min at moderate intensity and to exhaustion at severe intensity\\u000a before and 48 h after eccentric exercise (100 squats with a load corresponding to 70% of body mass). Changes in ventilation\\u000a and ratings of perceived

Rosemary C. Davies; Ann V. Rowlands; Roger G. Eston

2009-01-01

398

Exercise-induced rhabdomyolysis and transient loss of deambulation as outset of partial carnitine palmityl transferase II deficiency  

Microsoft Academic Search

We report the case of a 13-year-old boy with an abrupt onset of leg pain and muscle weakness, incapability of deambulation\\u000a and a laboratory picture of exercise-induced acute rhabdomyolysis. Intravenous hyperhydration and forced diuresis were adopted\\u000a to avoid renal complications. No evidence of articular or residual muscular damage was appreciated in the short-term. The\\u000a recurrence of rhabdomyolysis required a muscular

Donato Rigante; Giulia Bersani; Adele Compagnone; Anna Zampetti; Alessia De Nisco; Emanuela Sacco; Raffaella Marrocco

2011-01-01

399

Percutaneous arterial interventional treatment of exercise-induced neurogenic intermittent claudication due to ischaemia of the lumbosacral plexus  

Microsoft Academic Search

Radiological interventional therapy is described in seven patients with a distinct clinical syndrome of exercise-induced\\u000a neurogenic intermittent claudication due to a reversible ischaemia of the lumbosacral plexus during walking accompanied by\\u000a transient neurologic deficits. This condition was presumably caused by a reversible vascular steal phenomenon during exertion.\\u000a The underlying vascular conditions were stenoses of the internal and\\/or common iliac arteries.

Walter A. Wohlgemuth; Manfred Stoehr

2002-01-01

400

Endogenous opioid peptide responses to opioid and anti-inflammatory medications following eccentric exercise-induced muscle damage  

Microsoft Academic Search

To determine the effects of Vicoprofen®, Ibuprofen, and a placebo on the responses of endogenous opioid peptides following eccentric exercise-induced muscle damage 36 healthy men (age: 22.8 years; height: 178.8±6.2cm; body mass: 78.9±13.7kg; body fat: 15.8±6.5%) volunteered to participate in the study. Each participant was evalua