scholarly journals Exercise protects against doxorubicin-induced oxidative stress and proteolysis in skeletal muscle

2011 ◽  
Vol 110 (4) ◽  
pp. 935-942 ◽  
Author(s):  
Ashley J. Smuder ◽  
Andreas N. Kavazis ◽  
Kisuk Min ◽  
Scott K. Powers
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Antioxidant Enzymes ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Oxidative Damage ◽  
Muscle Fibers ◽  
Muscular Exercise ◽  
Protease Activation ◽  
Exercise Induced

Doxorubicin (Dox) is a potent antitumor agent used in cancer treatment. Unfortunately, Dox is myotoxic and results in significant reductions in skeletal muscle mass and function. Complete knowledge of the mechanism(s) by which Dox induces toxicity in skeletal muscle is incomplete, but it is established that Dox-induced toxicity is associated with increased generation of reactive oxygen species and oxidative damage within muscle fibers. Since muscular exercise promotes the expression of numerous cytoprotective proteins (e.g., antioxidant enzymes, heat shock protein 72), we hypothesized that muscular exercise will attenuate Dox-induced damage in exercise-trained muscle fibers. To test this postulate, Sprague-Dawley rats were randomly assigned to the following groups: sedentary, exercise, sedentary with Dox, or exercise with Dox. Our results show increased oxidative stress and activation of cellular proteases (calpain and caspase-3) in skeletal muscle of animals treated with Dox. Importantly, our findings reveal that exercise can prevent the Dox-induced oxidative damage and protease activation in the trained muscle. This exercise-induced protection against Dox-induced toxicity may be due, at least in part, to an exercise-induced increase in muscle levels of antioxidant enzymes and heat shock protein 72. Together, these novel results demonstrate that muscular exercise is a useful countermeasure that can protect skeletal muscle against Dox treatment-induced oxidative stress and protease activation in skeletal muscles.

scholarly journals Mitochondrial-targeted antioxidants protect skeletal muscle against immobilization-induced muscle atrophy

2011 ◽  
Vol 111 (5) ◽  
pp. 1459-1466 ◽  
Author(s):  
Kisuk Min ◽  
Ashley J. Smuder ◽  
Oh-sung Kwon ◽  
Andreas N. Kavazis ◽  
Hazel H. Szeto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscle Fibers ◽  
Skeletal Muscle Atrophy ◽  
Ros Production ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Protease Activation ◽  
Limb Immobilization

Prolonged periods of muscular inactivity (e.g., limb immobilization) result in skeletal muscle atrophy. Although it is established that reactive oxygen species (ROS) play a role in inactivity-induced skeletal muscle atrophy, the cellular pathway(s) responsible for inactivity-induced ROS production remain(s) unclear. To investigate this important issue, we tested the hypothesis that elevated mitochondrial ROS production contributes to immobilization-induced increases in oxidative stress, protease activation, and myofiber atrophy in skeletal muscle. Cause-and-effect was determined by administration of a novel mitochondrial-targeted antioxidant (SS-31) to prevent immobilization-induced mitochondrial ROS production in skeletal muscle fibers. Compared with ambulatory controls, 14 days of muscle immobilization resulted in significant muscle atrophy, along with increased mitochondrial ROS production, muscle oxidative damage, and protease activation. Importantly, treatment with a mitochondrial-targeted antioxidant attenuated the inactivity-induced increase in mitochondrial ROS production and prevented oxidative stress, protease activation, and myofiber atrophy. These results support the hypothesis that redox disturbances contribute to immobilization-induced skeletal muscle atrophy and that mitochondria are an important source of ROS production in muscle fibers during prolonged periods of inactivity.

scholarly journals Elevation in heat shock protein 72 mRNA following contractions in isolated single skeletal muscle fibers

2008 ◽  
Vol 295 (2) ◽  
pp. R642-R648 ◽  
Author(s):  
Creed M. Stary ◽  
Brandon J. Walsh ◽  
Amy E. Knapp ◽  
David Brafman ◽  
Michael C. Hogan
Keyword(s):  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Muscle Fibers ◽  
Stable Model ◽  
Heat Shock Protein 72 ◽  
Skeletal Muscle Fibers ◽  
Single Bout ◽  
Mrna Content ◽  
Fatiguing Contractions

The purpose of the present study was 1) to develop a stable model for measuring contraction-induced elevations in mRNA in single skeletal muscle fibers and 2) to utilize this model to investigate the response of heat shock protein 72 (HSP72) mRNA following an acute bout of fatiguing contractions. Living, intact skeletal muscle fibers were microdissected from lumbrical muscle of Xenopus laevis and either electrically stimulated for 15 min of tetanic contractions (EX; n = 26) or not stimulated to contract (REST; n = 14). The relative mean developed tension of EX fibers decreased to 29 ± 7% of initial peak tension at the stimulation end point. Following treatment, individual fibers were allowed to recover for 1 ( n = 9), 2 ( n = 8), or 4 h ( n = 9) prior to isolation of total cellular mRNA. HSP72, HSP60, and cardiac α-actin mRNA content were then assessed in individual fibers using quantitative PCR detection. Relative HSP72 mRNA content was significantly ( P < 0.05) elevated at the 2-h postcontraction time point relative to REST fibers when normalized to either HSP60 (18.5 ± 7.5-fold) or cardiac α-actin (14.7 ± 4.3-fold), although not at the 1- or 4-h time points. These data indicate that 1) extraction of RNA followed by relative quantification of mRNA of select genes in isolated single skeletal muscle fibers can be reliably performed, 2) HSP60 and cardiac α-actin are suitable endogenous normalizing genes in skeletal muscle following contractions, and 3) a significantly elevated content of HSP72 mRNA is detectable in skeletal muscle 2 h after a single bout of fatiguing contractions, despite minimal temperature changes and without influence from extracellular sources.

Acute and severe hypobaric hypoxia increases oxidative stress and impairs mitochondrial function in mouse skeletal muscle

2005 ◽  
Vol 99 (4) ◽  
pp. 1247-1253 ◽  
Author(s):  
José Magalhães ◽  
António Ascensão ◽  
José M. C. Soares ◽  
Rita Ferreira ◽  
Maria J. Neuparth ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Skeletal Muscle ◽  
Vitamin E ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Hypobaric Hypoxia ◽  
Sulfhydryl Group ◽  
Protein Carbonyls ◽  
Heat Shock Protein 60

Severe high-altitude hypoxia exposure is considered a triggering stimulus for redox disturbances at distinct levels of cellular organization. The effect of an in vivo acute and severe hypobaric hypoxic insult (48 h at a pressure equivalent to 8,500 m) on oxidative damage and respiratory function was analyzed in skeletal muscle mitochondria isolated from vitamin E-supplemented (60 mg/kg ip, 3 times/wk for 3 wk) and nonsupplemented mice. Forty male mice were randomly divided into four groups: control + placebo, hypoxia + placebo (H + P), control + vitamin E, and hypoxia + vitamin E. Significant increases in mitochondrial heat shock protein 60 expression and protein carbonyls group levels and decreases in aconitase activity and sulfhydryl group content were found in the H + P group when compared with the control + placebo group. Mitochondrial respiration was significantly impaired in animals from the H + P group, as demonstrated by decreased state 3 respiratory control ratio and ADP-to-oxygen ratio and by increased state 4 with both complex I- and II-linked substrates. Using malate + pyruvate as substrates, hypoxia decreased the respiratory rate in the presence of carbonyl cyanide m-chlorophenylhydrazone and also stimulated oligomycin-inhibited respiration. However, vitamin E treatment attenuated the effect of hypoxia on the mitochondrial levels of heat shock protein 60 and markers of oxidative stress. Vitamin E was also able to prevent most mitochondrial alterations induced by hypobaric hypoxia. In conclusion, hypobaric hypoxia increases mitochondrial oxidative stress while decreasing mitochondrial capacity for oxidative phosphorylation. Vitamin E was an effective preventive agent, which further supports the oxidative character of mitochondrial dysfunction induced by hypoxia.

Alpha-lipoic Acid Attenuates Exercise-induced Oxidative Stress And Enhances Heat Shock Protein Responses

2009 ◽  
Vol 41 ◽  
pp. 104-105
Author(s):  
Mustafa Atalay ◽  
Susanna Kinnunen ◽  
Niku Oksala ◽  
Seppo Hyyppä ◽  
Zsolt Radak ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Lipoic Acid ◽  
Alpha Lipoic Acid ◽  
Exercise Induced

Initiating treadmill training in late middle age offers modest adaptations in Ca2+ handling but enhances oxidative damage in senescent rat skeletal muscle

2010 ◽  
Vol 298 (5) ◽  
pp. R1269-R1278 ◽  
Author(s):  
Melissa M. Thomas ◽  
Chris Vigna ◽  
Andrew C. Betik ◽  
A. Russell Tupling ◽  
Russell T. Hepple
Keyword(s):  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Oxidative Damage ◽  
Heat Shock Protein 70 ◽  
Gastrocnemius Muscle ◽  
Middle Age ◽  
Treadmill Training ◽  
Brown Norway ◽  
Age Related

Aging skeletal muscle shows an increased time to peak force and relaxation and a decreased specific force, all of which could relate to changes in muscle Ca2+ handling. The purpose of this study was to determine if Ca2+-handling protein content and function are decreased in senescent gastrocnemius muscle and if initiating a training program in late middle age (LMA, 29 mo old) could improve function in senescent (34- to 36-mo-old) muscle. LMA male Fischer 344 × Brown-Norway rats underwent 5–7 mo of treadmill training. Aging resulted in a decrease in maximal sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity and a decrease in Ca2+ release rate but no change in Ca2+ uptake rate. Efficiency of the Ca2+ pump was increased with age, as was the content of SERCA2a. Training caused a further increase in SERCA2a content. Aging also caused an increase in protein carbonyl and reactive nitrogen species damage accumulation, and both further increased with training. Consistent with the increase in oxidative damage, heat shock protein 70 content was increased with age and further increased with training. Together, these results suggest that while initiating exercise training in LMA augments the age-related increase in expression of heat shock protein 70 and the more efficient SERCA2a isoform, it did not prevent the decrease in SERCA activity and exacerbated oxidative damage in senescent gastrocnemius muscle.

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