Invited Review: Contractile activity-induced mitochondrial biogenesis in skeletal muscle

2001 ◽  
Vol 90 (3) ◽  
pp. 1137-1157 ◽  
Author(s):  
David A. Hood
Keyword(s):  
Transcription Factors ◽  
Respiratory Chain ◽  
Mitochondrial Biogenesis ◽  
Adenine Nucleotide ◽  
Contractile Activity ◽  
Recovery Period ◽  
Atp Synthesis ◽  
Nucleotide Metabolism ◽  
Significant Shift ◽  
Mrna Levels

Chronic contractile activity produces mitochondrial biogenesis in muscle. This adaptation results in a significant shift in adenine nucleotide metabolism, with attendant improvements in fatigue resistance. The vast majority of mitochondrial proteins are derived from the nuclear genome, necessitating the transcription of genes, the translation of mRNA into protein, the targeting of the protein to a mitochondrial compartment via the import machinery, and the assembly of multisubunit enzyme complexes in the respiratory chain or matrix. Putative signals involved in initiating this pathway of gene expression in response to contractile activity likely arise from combinations of accelerations in ATP turnover or imbalances between mitochondrial ATP synthesis and cellular ATP demand, and Ca2+ fluxes. These rapid events are followed by the activation of exercise-responsive kinases, which phosphorylate proteins such as transcription factors, which subsequently bind to upstream regulatory regions in DNA, to alter transcription rates. Contractile activity increases the mRNA levels of nuclear-encoded proteins such as cytochrome c and mitochondrial transcription factor A (Tfam) and mRNA levels of upstream transcription factors like c- junand nuclear respiratory factor-1 (NRF-1). mRNA level changes are often most evident during the postexercise recovery period, and they can occur as a result of contractile activity-induced increases in transcription or mRNA stability. Tfam is imported into mitochondria and controls the expression of mitochondrial DNA (mtDNA). mtDNA contributes only 13 protein products to the respiratory chain, but they are vital for electron transport and ATP synthesis. Contractile activity increases Tfam expression and accelerates its import into mitochondria, resulting in increased mtDNA transcription and replication. The result of this coordinated expression of the nuclear and the mitochondrial genomes, along with poorly understood changes in phospholipid synthesis, is an expansion of the muscle mitochondrial reticulum. Further understanding of 1) regulation of mtDNA expression, 2) upstream activators of NRF-1 and other transcription factors, 3) the identity of mRNA stabilizing proteins, and 4) potential of contractile activity-induced changes in apoptotic signals are warranted.

Regulation of Egr-1, SRF, and Sp1 mRNA expression in contracting skeletal muscle cells

2004 ◽  
Vol 97 (6) ◽  
pp. 2207-2213 ◽  
Author(s):  
Isabella Irrcher ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factors ◽  
Mrna Expression ◽  
Mitochondrial Biogenesis ◽  
Contractile Activity ◽  
Recovery Period ◽  
Muscle Cells ◽  
Skeletal Muscle Cells ◽  
Mrna Levels ◽  
Serum Response

The early cellular signals associated with contractile activity initiate the activation and induction of transcription factors that regulate changes in skeletal muscle phenotype. The transcription factors Egr-1, Sp1, and serum response factor (SRF) are potentially important mediators of mitochondrial biogenesis based on the prevalence of binding sites for them in the promoter regions of genes encoding mitochondrial proteins, including PGC-1α, the important regulator of mitochondrial biogenesis. Thus, to further define a role for transcription factors at the onset of contractile activity, we examined the time-dependent alterations in Egr-1, Sp1, and SRF mRNA and the levels in electrically stimulated mouse C2C12 skeletal muscle cells. Early transient increases in Egr-1 mRNA levels within 30 min ( P < 0.05) of contractile activity led to threefold increases ( P < 0.05) in Egr-1 protein by 60 min. The increase in Egr-1 mRNA was not because of increased stability, as Egr-1 mRNA half-life after 30 min of stimulation showed only a 58% decline. Stimulation of muscle cells had no effect on Sp1 mRNA but led to progressive increases ( P < 0.05) in SRF mRNA by 30 and 60 min. This was not matched by increases in SRF protein but occurred coincident with increases ( P < 0.05) in SRF-serum response element DNA binding at 30 and 60 min as a result of SRF phosphorylation on serine-103. To assess the importance of the recovery period, 12 h of continuous contractile activity was compared with four successive 3-h bouts, with an intervening 21-h recovery period after each bout. Continuous contractile activity led to a twofold increase ( P < 0.05) in Egr-1 mRNA, no change in SRF mRNA, and a 43% decrease in Sp1 mRNA expression. The recovery period prevented the decline in Sp1 mRNA, produced a decrease in Egr-1 mRNA, and had no effect on SRF mRNA. Thus continuous and intermittent contractile activity evoked different specific transcription factor expression patterns, which may ultimately contribute to divergent qualitative, or temporal patterns of, phenotypic adaptation in muscle.

Selected Contribution: Effects of contractile activity on mitochondrial transcription factor A expression in skeletal muscle

2001 ◽  
Vol 90 (1) ◽  
pp. 389-396 ◽  
Author(s):  
Joe W. Gordon ◽  
Arne A. Rungi ◽  
Hidetoshi Inagaki ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Transcription Factor ◽  
Mitochondrial Biogenesis ◽  
Contractile Activity ◽  
Regulatory Protein ◽  
Mrna Levels ◽  
Mitochondrial Transcription ◽  
Mitochondrial Transcription Factor ◽  
Mitochondrial Transcription Factor A ◽  
Mitochondrial Transcript

Mitochondrial transcription factor A (Tfam) is a nuclear-encoded gene product that is imported into mitochondria and is required for the transcription of mitochondrial DNA (mtDNA). We hypothesized that conditions known to produce mitochondrial biogenesis in skeletal muscle would be preceded by an increase in Tfam expression. Therefore, rat muscle was stimulated (10 Hz, 3 h/day). Tfam mRNA levels were significantly elevated (by 55%) at 4 days and returned to control levels at 14 days. Tfam import into intermyofibrillar (IMF) mitochondria was increased by 52 and 61% ( P < 0.05) at 5 and 7 days, respectively. This corresponded to an increase in the level of import machinery components. Immunoblotting data indicated that IMF Tfam protein content was increased by 63% ( P < 0.05) at 7 days of stimulation. This was associated with a 49% ( P < 0.05) increase in complex formation at the mtDNA promoter and a 65% ( P< 0.05) increase in the levels of a mitochondrial transcript, cytochrome- c oxidase (COX) subunit III. Similarly, COX enzyme activity was elevated by 71% ( P < 0.05) after 7 days of contractile activity. These results indicate that early events in mitochondrial biogenesis include increases in Tfam mRNA, followed by accelerations in mitochondrial import and increased Tfam content, which correspond with increased binding to the mtDNA promoter region. This was accompanied by increased mitochondrial transcript levels and elevated COX activity. These data support the role of Tfam as a regulatory protein involved in contractile activity-induced mitochondrial biogenesis.

Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans

2000 ◽  
Vol 88 (5) ◽  
pp. 1513-1519 ◽  
Author(s):  
S. Zhao ◽  
R. J. Snow ◽  
C. G. Stathis ◽  
M. A. Febbraio ◽  
M. F. Carey
Keyword(s):  
Adenine Nucleotide ◽  
Vastus Lateralis ◽  
Recovery Period ◽  
Nucleotide Metabolism ◽  
Peak Oxygen Consumption ◽  
Vastus Lateralis Muscle ◽  
Adenine Nucleotide Metabolism ◽  
Exercise Induced ◽  
Adenine Nucleotide Pool ◽  
The Relationship

The relationship between changes in the muscle total adenine nucleotide pool (TAN = ATP + ADP + AMP) and IMP during and after 30 s of sprint cycling was examined. Skeletal muscle samples were obtained from the vastus lateralis muscle of seven untrained men (23.9 ± 2.3 yr, 74.4 ± 3.6 kg, and 55.0 ± 2.9 ml ⋅ kg−1 ⋅ min−1peak oxygen consumption) before and immediately after exercise and after 5 and 10 min of passive recovery. The exercise-induced increase in muscle IMP was linearly related to the decrease in muscle TAN ( r = −0.97, P < 0.01), and the slope of this relationship (−0.83) was not different from 1.0 ( P > 0.05), indicating a 1:1 stoichiometric relationship. This interpretation must be treated cautiously, because all subjects displayed a greater decrease in TAN compared with the increase in IMP content, and the TAN + IMP + inosine + hypoxanthine content was lower ( P < 0.05) immediately after exercise compared with during rest. During the first 5 min of recovery, the increase in TAN was not correlated with the decrease in IMP ( r = −0.18, P> 0.05). In all subjects, the magnitude of TAN increase was higher than the magnitude of IMP decrease over this recovery period. In contrast, the increase in TAN was correlated with the decrease in IMP throughout the second 5 min of recovery ( r = −0.80, P < 0.05), and it was a 1:1 stoichiometric relationship (slope = −1.12). These data indicate that a small proportion of the TAN pool was temporarily lost from the muscle purine stores during sprinting but was rapidly recovered after exercise.

AML Cells Have Altered Mitochondrial Biogenesis and Low Spare Reserve Capacity in Their Respiratory Chain That Renders Them Susceptible to Oxidative Metabolic Stress.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2581-2581
Author(s):  
Shrivani Sriskanthadevan ◽  
Timothy E Chung ◽  
Marko Skrtic ◽  
Bozhena Jhas ◽  
Rose Hurren ◽  
...  
Keyword(s):  
Oxygen Consumption ◽  
Respiratory Chain ◽  
Mitochondrial Biogenesis ◽  
Hematopoietic Cells ◽  
Atp Synthesis ◽  
Reserve Capacity ◽  
Complex Activity ◽  
Normal Cells ◽  
Mitochondrial Mass ◽  
Respiratory Complexes

Abstract Abstract 2581 Oxidative metabolism generates intracellular energy and metabolic intermediates necessary to promote the growth of AML cells. Recently, we demonstrated that AML cells are uniquely sensitive to inhibition of mitochondrial translation. Therefore, we characterized the structure and metabolic function of the mitochondria in AML and normal hematopoietic cells. Compared to normal cells (n = 10), 1° AML cells (n = 12) had increased mitochondrial mass and increased levels of the NRF-1, TFAM, EF-Tu and Myc, genes that positively regulate mitochondrial biogenesis. By transmission electron microscopy, we demonstrated that the mitochondria in 1°AML cells were larger in area, but fewer in number compared to normal CD34+ cells. Given the dysregulated mitochondrial biogenesis in 1° AML cells, we examined the activity and reserve capacity of the respiratory complexes in 1° AML and normal cells. When normalized for mitochondrial mass, 1°AML cells (n = 12) had reduced activity of respiratory complexes III, IV and V compared to normal cells (n = 10). Thus, despite the increased mitochondrial mass in AML, respiratory chain complex activity did not increase proportionately. Next, we evaluated the spare reserve capacity in AML cell lines, 1° AML samples, and normal cells. Spare reserve capacity reflects the difference between basal and maximal respiratory rate and was determined by measuring oxygen consumption after treatment with oligomycin to block ATP synthesis and FCCP to uncouple ATP synthesis from the electron transport chain. The spare reserve capacity in AML cells and 1o samples was lower than normal hematopoietic cells. In order to determine the reserve capacity in individual respiratory complexes, we evaluated the rate of oxygen consumption in 1°AML and normal cells by treating the cells with increasing concentrations of the complex I, III IV, and V inhibitors, rotenone, antimycin, sodium azide, and oligomycin, respectively, and measuring changes in oxygen consumption. AML cells displayed less reserve capacity in the individual complexes compared to normal hematopoietic cells, and the differences were most striking for complexes III and IV. Consistent with the reduced reserve capacity, AML cells were more sensitive to respiratory chain inhibitors. We then employed a genetic approach to investigate the relationship between mitochondrial mass and spare reserve capacity using P493 Burkitt's cells with inducible myc as we and others have previously shown that myc regulates mitochondrial mass. Compared to myc knockdown cells, myc +P493 cells had increased mitochondrial mass, larger mitochondria, increased basal oxygen consumption, but reduced activity of respiratory complexes III, IV and V when normalized for mitochondrial mass, compared to myc - cells. In addition, myc expressing cells had less spare reserve capacity in their respiratory chain. Thus, in this isogenic cell line, increased mitochondrial mass was not accompanied by a proportionate increase in respiratory chain activity resulting in decreased spare reserve capacity. Given the reduced reserve capacity in AML cells, we evaluated the effects of increasing electron flux through respiratory chain. We speculated that the low spare reserve capacity would render AML cells more vulnerable to oxidative stress. To test this strategy AML cells and 1° samples as well as normal cells were treated increasing concentrations of the fatty acid substrate palmitate or the TCA cycle substrate dimethyl succinate. Consistent with our hypothesis, treatment with palmitate or dimethyl succinate transiently increased oxygen consumption and decreased spare reserve capacity in AML but not normal cells. Subsequently these treatments, increased reactive oxygen and induced cell death preferentially in AML cells and 1° samples compare to normal hematopoietic cells. Moreover, this treatment preferentially reduced the clonogenic growth of 1° AML cells over normal cells and reduced the engraftment of 1°AML but not normal cells into immune deficient mice. In summary, compared to normal hematopoietic cells, AML cells have greater mitochondrial mass but respiratory chain activity does not increase proportionately. The lack of proportionate rise in respiratory complex activity results in reduced spare reserve capacity in the respiratory complexes and greater sensitivity to oxidative stress. These data highlight a unique metabolic vulnerability in AML. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Control of adenine nucleotide metabolism in hepatic mitochondria from rats with ethanol-induced fatty liver

1982 ◽  
Vol 202 (2) ◽  
pp. 445-452 ◽  
Author(s):  
Priscilla I. Spach ◽  
Ralph E. Bottenus ◽  
Carol C. Cunningham
Keyword(s):  
Fatty Liver ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Respiratory Control ◽  
Atp Synthesis ◽  
Liver Mitochondria ◽  
Nucleotide Metabolism ◽  
Male Rats ◽  
Chain Acyl ◽  
Ethanol Feeding

Male rats developed fatty liver after being fed on an ethanol-containing diet for 31 days. Liver mitochondria from these animals catalysed ATP synthesis at a slower rate when compared with mitochondria from pair-fed control rats (control mitochondria), and demonstrated lowered respiratory control with succinate as substrate, owing to a decrease in the State-3 respiratory rate. Respiration in the presence of uncoupler was comparable in mitochondria from both groups of rats. Translocation of both ATP and ADP was decreased in mitochondria from ethanol-fed rats, with ADP uptake being lowered more dramatically by ethanol feeding. Parameters influencing adenine nucleotide translocation were investigated in mitochondria from ethanol-fed rats. Experiments performed suggested that lowered adenine nucleotide translocation in these mitochondria is not the result of inhibition of the translocase by either long-chain acyl-CoA derivatives or unesterified fatty acids. Analysis of endogenous adenine nucleotides in these mitochondria revealed lowered ATP concentrations, but no decrease in total adenine nucleotides. In experiments where the endogenous ATP in these mitochondria was shifted to higher concentrations by incubation with oxidizable substrates or defatted bovine serum albumin, the rate of ADP translocation was increased, with a linear correlation being observed between endogenous ATP concentrations and the rate of ADP translocation. The depressed ATP concentration in mitochondria from ethanol-fed rats suggests that the ATP synthetase complex is replenishing endogenous ATP at a slower rate. The lowered ATPase activity of the ATP synthetase observed in submitochondrial particles from ethanol-fed animals suggests a decrease in the function of the synthetase complex. A decrease in the rate of ATP synthesis in mitochondria from ethanol-fed rats is sufficient to explain the decreased ADP translocation and State-3 respiration.

Increases of cell ATP produced by exogenous adenine nucleotides in isolated rabbit kidney tubules

1986 ◽  
Vol 250 (4) ◽  
pp. F720-F733 ◽  
Author(s):  
J. M. Weinberg ◽  
H. D. Humes
Keyword(s):  
Cell Injury ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Recovery Period ◽  
Nucleotide Metabolism ◽  
Rabbit Kidney ◽  
Kidney Tubules ◽  
Atp Levels ◽  
Adenine Nucleotide Metabolism ◽  
Functional Consequences

The effects of exogenous nucleotides on adenine nucleotide metabolism and cell cation levels in normal and O2-deprived isolated rabbit kidney tubules were studied to gain insight into ways in which exogenous nucleotides could contribute to ameliorating O2 deprivation-induced injury. In control oxygenated tubules, 250 microM exogenous ATP, ADP, or AMP resulted in two- to threefold increases of cell ATP over 75-90 min of incubation and smaller relative increases of ADP and AMP. GTP was not increased. Exogenous adenosine, inosine, and hypoxanthine were substantially less effective at increasing intracellular nucleotides than equimolar concentrations of exogenous nucleotides. Nucleotide-treated cells had higher levels of Ca2+ and Mg2+ than untreated cells. Treatment of O2-deprived tubules with exogenous Mg-ATP improved recovery of ATP levels following O2 deprivation, and tubules with mild injury increased their ATP levels to supranormal values such as those seen in control oxygenated tubules treated with nucleotides. Increases of tubule cell ATP levels required ongoing oxidative metabolism and thus were not evident until the reoxygenation recovery period. Exogenous ATP produced some improvement of other injury-associated metabolic parameters but did not substantially alter the overall pattern of tubule susceptibility to lethal cell injury. Allopurinol did not affect the behavior of oxygenated or O2-deprived tubules irrespective of the presence of exogenous ATP. These data clarify the potential for manipulating intracellular ATP levels with exogenous nucleotides and the functional consequences of such manipulation in oxygenated and O2-deprived renal tubule cells.

scholarly journals Effect of contractile activity on PGC-1α transcription in young and aged skeletal muscle

2018 ◽  
Vol 124 (6) ◽  
pp. 1605-1615 ◽  
Author(s):  
Heather N. Carter ◽  
Marion Pauly ◽  
Liam D. Tryon ◽  
David A. Hood
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Transcription Factor ◽  
Mitochondrial Biogenesis ◽  
Acute Exercise ◽  
Contractile Activity ◽  
Expression Patterns ◽  
Recovery Period ◽  
Peroxisome Proliferator ◽  
Altered Expression

Mitochondrial impairments are often noted in aged skeletal muscle. The transcriptional coactivator peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is integral to maintaining mitochondria, and its expression declines in aged muscle. It remains unknown whether this is due to a transcriptional deficit during aging. Our study examined PGC-1α transcription in muscle from young and old F344BN rats. Using a rat PGC-1α promoter-reporter construct, we found that PGC-1α transcription was reduced by ∼65% in aged TA muscle, accompanied by decreases in PGC-1α mRNA and transcript stability. Altered expression patterns in PGC-1α transcription regulatory factors, including nuclear respiratory factor 2, upstream transcription factor 1, activating transcription factor 2, and yin yang 1, were noted in aged muscle. Acute contractile activity (CA) followed by recovery was employed to examine whether PGC-1α transcription could be activated in aged muscle similar to that observed in young muscle. AMPK and p38 signaling was attenuated in aged muscle. CA evoked an upregulation of PGC-1α transcription in both young and aged groups, whereas mRNAs encoding PGC-1α and cytochrome oxidase subunit IV were induced during the recovery period. Global DNA methylation, an inhibitory event for transcription, was enhanced in aged muscle, likely a result of elevated methyltransferase enzyme Dnmt3b in aged muscle. Successive bouts of CA for 7 days to evaluate longer-term consequences resulted in a rescue of PGC-1α and downstream mRNAs in aged muscle. Our data indicate that diminished mitochondria in aged muscle is due partly to a deficit in PGC-1α transcription, a result of attenuated upstream signaling. Contractile activity is an appropriate countermeasure to restore PGC-1α expression and mitochondrial content in aged muscle. NEW & NOTEWORTHY PGC-1α is a regulator of mitochondrial biogenesis in muscle. We demonstrate that PGC-1α expression is reduced in aging muscle due to decreases in transcriptional and posttranscriptional mechanisms. The transcriptional deficit is due to alterations in transcription factor expression, reduced signaling, and DNA methylation. Acute exercise can initiate signaling to reverse the transcriptional defect, restoring PGC-1α expression toward young values, suggesting a mechanism whereby aged muscle can respond to exercise for the promotion of mitochondrial biogenesis.

scholarly journals Hypothermia preserves function and signaling for mitochondrial biogenesis during subsequent ischemia

1998 ◽  
Vol 274 (3) ◽  
pp. H786-H793 ◽  
Author(s):  
Xue-Han Ning ◽  
Cheng-Su Xu ◽  
Ying C. Song ◽  
Yun Xiao ◽  
Ying-Jia Hu ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Protein ◽  
Mitochondrial Biogenesis ◽  
Stress Responses ◽  
Adenine Nucleotide ◽  
Left Ventricular Pressure ◽  
Left Ventricular ◽  
Control Group ◽  
Ischemia And Reperfusion ◽  
Mrna Levels

Hypothermia is known to protect myocardium during ischemia, but its role in induction of a protective stress response before ischemia has not been evaluated. As cold incites stress responses in other tissues, including heat shock protein induction and signaling mitochondrial biogenesis, we postulated that hypothermia in perfused hearts would produce similar phenomena while reducing injury during subsequent ischemia. Studies were performed in isolated perfused rabbit hearts ( n = 77): a control group (C) and a hypothermic group (H) subjected to decreasing infusate temperature from 37 to 31°C over 20 min. Subsequent ischemia during cardioplegic arrest at 34°C for 120 min was followed by reperfusion. At 15 min of reperfusion, recovery of left ventricular developed pressure (LVDP), maximum first derivative of left ventricular pressure (LV dP/d tmax), LV −dP/d tmax, and the product of heart rate and LVDP was significantly increased in H ( P < 0.01) compared with C hearts. Ischemic contracture started later in H (97.5 ± 3.6 min) than in C (67.3 ± 3.3 min) hearts. Myocardial ATP preservation and repletion during ischemia and reperfusion were higher in H than in C hearts. mRNA levels of the nuclear-encoded mitochondrial proteins adenine nucleotide translocase isoform 1 (ANT1) and β-F1-adenosinetriphosphatase (β-F1-ATPase) normalized to 28S RNA decreased in C hearts but were preserved in H hearts after reperfusion. Inducible heat shock protein (HSP70–1) mRNA was elevated nearly 4-fold after ischemia in C hearts and 12-fold in H hearts. These data indicate that hypothermia preserves myocardial function and ATP stores during subsequent ischemia and reperfusion. Signaling for mitochondrial biogenesis indexed by ANT1and β-F1-ATPase mRNA levels is also preserved during a marked increase in HSP70–1 mRNA.

Effect of contractile activity on protein turnover in skeletal muscle mitochondrial subfractions

2000 ◽  
Vol 88 (5) ◽  
pp. 1601-1606 ◽  
Author(s):  
Michael K. Connor ◽  
Olga Bezborodova ◽  
C. Patricia Escobar ◽  
David A. Hood
Keyword(s):  
Mitochondrial Biogenesis ◽  
Protein Turnover ◽  
Gastrocnemius Muscle ◽  
Contractile Activity ◽  
Recovery Period ◽  
Chronic Stimulation ◽  
Fast Twitch ◽  
Isolated Rat

To determine the role of intramitochondrial protein synthesis (PS) and degradation (PD) in contractile activity-induced mitochondrial biogenesis, we evaluated rates of [35S]methionine incorporation into protein in isolated rat muscle subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondria. Rates of PS ranged from 47 to 125% greater ( P < 0.05) in IMF compared with SS mitochondria. Intense, acute in situ contractile activity (10 Hz, 5 min) of fast-twitch gastrocnemius muscle resulted in a 50% decrease in PS ( P < 0.05) in SS but not IMF mitochondria. Recovery, or continued contractile activity (55 min), reestablished PS in SS mitochondria. In contrast, PS was not affected in either SS or IMF mitochondria after prolonged (60-min) contractile activity in the presence or absence of a recovery period. PD was not influenced by 5 min of contractile activity in the presence or absence of recovery but was reduced after 60 min of contractions followed by recovery. Chronic stimulation (10 Hz, 3 h/day, 14 days) increased muscle cytochrome- c oxidase activity by 2.2-fold but reduced PS in IMF mitochondria by 29% ( P < 0.05; n = 4). PS in SS mitochondria and PD in both subfractions were not changed by chronic stimulation. Thus acute contractile activity exerts differential effects on protein turnover in IMF and SS mitochondria, and it appears that intramitochondrial PS does not limit the extent of chronic contractile activity-induced mitochondrial biogenesis.

MRF4, Myf-5, and myogenin mRNAs in the adaptive responses of mature rat muscle

1995 ◽  
Vol 268 (4) ◽  
pp. C1045-C1052 ◽  
Author(s):  
J. Jacobs-El ◽  
M. Y. Zhou ◽  
B. Russell
Keyword(s):  
Contractile Activity ◽  
Tibialis Anterior Muscle ◽  
Recovery Period ◽  
Low Frequency ◽  
Female Rats ◽  
Positive Staining ◽  
Mrna Levels ◽  
Adaptive Responses ◽  
Static Stretch

We studied the possible role of specific muscle regulatory factors (MRF) in the adaptive response to changes in contractile activity in mature skeletal muscle. The tibialis anterior muscle of anesthetized female rats was subjected to low-frequency stimulation, static stretch, or a combination of both. Message levels of MRF were observed after 2 h of activity, and the subsequent 20-h recovery period by slot blot and in situ hybridizations for MRF4, Myf-5, and myogenin. A combination of stimulation and stretch for 2 h increased MRF4 (11.6 +/- 5.3-fold) and Myf-5 (6.6 +/- 1.4-fold). In situ hybridization showed abundance in some regions of the muscle with positive staining near peripheral nuclei of both large and small fibers. Message levels remained high for 30 min and declined to near control levels by 20 h of recovery. Myogenin mRNA levels were unaffected by any manipulations. Neither stretch alone nor 10 Hz of electrical stimulation alone induced a significant increase in MRF. We conclude that myonuclei, and possibly activated myoblasts, increase expression of Myf-5 and MRF4 after a combination of both stimulation and stretch for 2 h.

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