Heat Shock Proteins In Skeletal Muscle Research Articles

Skeletal Muscle Heat Shock Protein Content and the Repeated Bout Effect.

The "Repeated Bout Effect" (RBE) occurs when a skeletal muscle is preconditioned with a few lengthening contractions (LC) prior to exposing the muscle to a greater number of LC. The preconditioning (PC) results in significantly less damage and preservation of force. Since it takes only a few LC to increase muscle heat shock protein (HSP) content, it was of interest to examine the relationship between HSPs and the RBE. To do this, one tibialis anterior (TA) muscle from Sprague-Dawley rats (n = 5/group) was preconditioned with either 0, 5, or 15 lengthening contractions (LC) and exposed to a treatment of 60 LC 48 h later. Preconditioning TA muscles with 15 LC, but not 5 LC, significantly elevated muscle αB-crystallin (p < 0.05), HSP25 (p < 0.05), and HSP72 content (p < 0.001). These preconditioned TA muscles also showed a significantly (p < 0.05) reduced loss of active torque throughout the subsequent 60 LC. While there was a trend for all preconditioned muscles to maintain higher peak torque levels throughout the 60 LC, no significant differences were detected between the groups. Morphologically, preconditioned muscles appeared to show less discernible muscle fiber damage. In conclusion, an elevated skeletal muscle HSP content from preconditioning may contribute to the RBE.

Ad Libitum Western Diet Feeding Does Not Alter Basal Skeletal Muscle Heat Shock Protein Expression in Sedentary or Aerobically Trained Young Rats

Poor dietary habits can lead to obesity and insulin resistance—both of which can impair basal heat shock protein (HSP) expression and the HSP stress response in skeletal muscle. It remains unclear if impairments in HSP expression occur during the early stages of diet-induced obesity and metabolic dysfunction. We determined if basal HSP expression (HSP70, HSP60, HSP25) was impaired in sedentary or exercised rats following the onset of diet-induced obesity. Male Long-Evans rats (N=6-7/group) were assigned to a Western diet (WD) or purified diet (PD). Animals were divided into sedentary (WD and PD) or exercise-trained (WD+Ex and PD+Ex) groups and fed &lt;/span&gt;&lt;em&gt;&lt;span&gt;ad libitum&lt;/span&gt;&lt;/em&gt;&lt;span&gt; for 12-weeks. WD animals displayed higher body mass, fat mass, blood glucose, and HOMA-IR scores compared to PD (p&lt;0.05). Exercise attenuated elevations in HOMA-IR and body mass for WD+Ex (p&gt;0.05) but did not prevent elevations in fat mass or blood glucose when compared to controls. Basal HSP (HSP70, HSP60, HSP25) expression was not impaired in sedentary WD animals when compared to PD (p&gt;0.05) or when WD+Ex was compared to PD+Ex (p&gt;0.05). Exercise training elevated HSP70 expression in the gastrocnemius muscle (GAST) (p&lt;0.05), but not in the soleus (SOL) (p&gt;0.05) in WD+Ex and PD+Ex animals. HSP60 and pHSP25 were unaffected by exercise training (GAST and SOL, p&gt;0.05). The onset of diet-induced obesity does not impair skeletal muscle HSP expression in sedentary or exercised animals. Thus, obesity and symptomology of metabolic dysfunction may occur before reductions in skeletal muscle HSP expression.

HSP72 expression is specific to skeletal muscle contraction type.

Exercise is capable of inducing the cellular stress response and increasing skeletal muscle heat shock protein (HSP) content. HSPs function as molecular chaperones and play roles in facilitating protein folding thereby contributing to muscle proteostasis. To determine the relationship between muscle contraction types, muscle damage, and HSP content, one tibialis anterior (TA) muscle from male Sprague-Dawley rats (n = 5/group) was electrically stimulated while actively lengthening (LC), shortening (SC), or remaining to stagnate (IC) for 15 repetitions (3 sets of five). Two additional LC groups underwent 5 and 10 repetitions. Maximal tetanic tension (MTT) was recorded prior to (pre) and at 5min after (post) the last contraction. Twenty-four hours after stimulation, TA muscles were removed, processed, and assessed for damage and for HSP25 and HSP72 content. Post-MTT was significantly decreased following 15 LCs, (24%; p < 0.05) but not following 15 SCs or 15 ICs. Post-MTT was also decreased by 8% (p < 0.05), and 18% (p < 0.05) for muscles subjected to 5 and 10 LCs, respectively. HSP72 content increased after all LCs conditions but not following ICs or SCs. HSP25 content remained unchanged following all contractions. Similarly, muscle damage was observed only after LCs and not after other contraction types. In conclusion, muscle HSP72 content can be increased with as few as 5 maximal lengthening contractions and appears to be related to muscle damage. This may have important implications for muscle rehabilitation and exercise training programs.

Heat therapy promotes the expression of angiogenic regulators in human skeletal muscle.

Heat therapy has been shown to promote capillary growth in skeletal muscle and in the heart in several animal models, but the effects of this therapy on angiogenic signaling in humans are unknown. We evaluated the acute effect of lower body heating (LBH) and unilateral thigh heating (TH) on the expression of angiogenic regulators and heat shock proteins (HSPs) in healthy young individuals. Exposure to LBH (n = 18) increased core temperature (Tc) from 36.9 ± 0.1 to 37.4 ± 0.1°C (P < 0.01) and average leg skin temperature (Tleg) from 33.1 ± 0.1 to 39.6 ± 0.1°C (P < 0.01), but did not alter the levels of circulating angiogenic cytokines and bone marrow-derived proangiogenic cells (CD34(+)CD133(+)). In skeletal muscle, the change in mRNA expression from baseline of vascular endothelial growth factor (VEGF), angiopoietin 2 (ANGPT2), chemokines CCL2 and CX3CL1, platelet factor-4 (PF4), and several members of the HSP family was higher 30 min after the intervention in the individuals exposed to LBH (n = 11) compared with the control group (n = 12). LBH also reduced the expression of transcription factor FOXO1 (P = 0.03). Exposure to TH (n = 14) increased Tleg from 32.8 ± 0.2 to 40.3 ± 0.1°C (P < 0.05) but Tc remained unaltered (36.8 ± 0.1°C at baseline and 36.9 ± 0.1°C at 90 min). This intervention upregulated the expression of VEGF, ANGPT1, ANGPT2, CCL2, and HSPs in skeletal muscle but did not affect the levels of CX3CL1, FOXO-1, and PF4. These findings suggest that both LBH and TH increase the expression of factors associated with capillary growth in human skeletal muscle.

Exercise Induces Skeletal Muscle Heat Shock Protein Expression Independent of Dietary Macronutrient Content

Diet‐induced obesity is directly associated with the development of hyperglycemia and stress kinase activation in target tissues, leading to impaired glucose tolerance and insulin resistance (IR) in skeletal muscle. Heat shock protein (HSP) induction is shown to attenuate the development of hyperglycemia and IR by precluding the activation of stress kinases. While HSP‐mediated improvements in metabolic function are observed with acute heat treatment, little is known about the effects of other known inducers of HSPs in skeletal muscle such as exercise and dietary modification. Therefore, the objective of this study was to compare the effects of dietary modification and chronic exercise on skeletal muscle HSP expression and fasting blood glucose levels (GLUC) in rats. Male Long‐Evans rats (N=27), were randomly assigned into Western diet (WD, 40% FAT/43% CHO/17% PRO) or vegan style Daniel Fast diet (DF, 25% FAT/60% CHO/15% PRO) groups. Rats were further divided into exercise (+EX) (25m·min−1 for 35 min·day−1, 3X/week) and sedentary groups. All rats were fed ad libitum for a 12 week intervention period. Soleus and gastrocnemius tissues were harvested and analyzed via western immunoblotting and densitometry for HSP70, pHSP27, HSP27, and HSP60 content. GLUC was measured using a standard enzymatic colorimetric assay. A two‐way ANOVA, with Tukey's post hoc test, was used to examine the differences in HSP expression between the diet and exercise groups for each tissue. A Pearson product‐moment correlation was used to determine if there was an association between HSP expression and GLUC. After 12 weeks of chronic exercise and dietary modification, gastrocnemius samples from the WD+EX and DF+EX groups had significant (P &lt; 0.05) increases in HSP70 expression (+194% and +196% respectively) in comparison to sedentary controls. Non‐significant changes in HSP70 expression were also seen in the soleus of WD+EX (+140%) and DF+EX (+185%) groups. There was no change in pHSP27, HSP27, and HSP60 due to exercise for both gastrocnemius and soleus tissues. Additionally, no change in HSP expression (HSP70, pHSP27, HSP27, and HSP60) was observed when comparing diets (WD:DF, WD+EX:DF+EX) for either tissue. GLUC values in the WD (183.47 mg/dL ± 18.27), WD+EX (158.34 mg/dL ± 24.39), and DF (129.34 mg/dL ± 22.86) groups were indicative of rats being hyperglycemic, while values in the DF+EX (112.95 mg/dL ± 7.19) group were within the normal physiologic range. Unlike previous reports, no correlation was observed between HSP expression and the degree of hyperglycemia (HSP70:GLUC, r = −.139). In conclusion, our data suggests that chronic exercise induces a uniform increase in HSP70 expression in rats fed either a Western diet or vegan style Daniel Fast diet. As such, exercise may be an effective means to obtain the therapeutic effects of HSP expression in hyperglycemic rats regardless of dietary macronutrient content.

Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 α1 expression.

Heat shock protein 60 (Hsp60) is a chaperone localizing in skeletal muscle mitochondria, whose role is poorly understood. In the present study, the levels of Hsp60 in fibres of the entire posterior group of hindlimb muscles (gastrocnemius, soleus, and plantaris) were evaluated in mice after completing a 6-week endurance training program. The correlation between Hsp60 levels and the expression of four isoforms of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC1α) were investigated only in soleus. Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperone could have a role in the activation of the expression levels of PGC1α isoforms. The levels of Hsp60 protein were fibre-type specific in the posterior muscles and endurance training increased its content in type I muscle fibers. Concomitantly with the increased levels of Hsp60 released in the blood stream of trained mice, mitochondrial copy number and the expression of three isoforms of PGC1α increased. Overexpressing hsp60 in cultured myoblasts induced only the expression of PGC1 1α, suggesting a correlation between Hsp60 overexpression and PGC1 1 α activation.

Skeletal muscle heat shock protein 60 increases after endurance training in mice and induces peroxisome proliferation-activated receptor-γ coactivator-1 α1 expression

Heat shock protein (Hsp60) is a mitochondrial chaperonin whose unconventional cellular localizations and functions are discovered day by day. In the present study, the levels of Hsp60 in fibres of the soleus muscle and its correlation to the expression of four isoforms of peroxisome proliferation-activated receptor-γ (PPAR-γ) coactivator-1α (PGC1α) were investigated in 72 young (7-weeks old) healthy male mice (BALB/c AnNHsd) at baseline and after completing a 6-week endurance training program. The mice were assigned to one of the two experimental groups: SED (sedentary) or TR (trained). Short-term overexpression of hsp60, achieved by in vitro plasmid transfection, was then performed to determine whether this chaperonin could have a role in the activation of the expression levels of PGC-1α isoforms. The levels of Hsp60 protein were fibre-type specific in the posterior muscles at baseline, and endurance training increased its content in type I muscle fibers. Concomitantly with the increased levels of Hsp60 released in the blood stream of trained mice, mitochondrial copy number and the expression of three isoforms of PGC-1α increased. Overexpressing hsp60 in cultured myoblasts induced only the expression of PGC-1 α1, letting us suppose a direct correlation between Hsp60 overexpression and PGC-1 α1 activation. Overall, these results suggest that during endurance training Hsp60 is upregulated and activates the mitochondrial biogenesis pathway, probably as a response to the oxidative stress induced by exercise. This study reveals a molecular response of skeletal muscle to a mechanical stress induced by training which involves the molecular chaperonin Hsp60 and the transcriptional co-activator PGC-1 α1. The role of these proteins in aerobic adaptation and pathological conditions as cancer cachexia warrants further investigations.

Dietary antioxidants at supranutritional doses modulate skeletal muscle heat shock protein and inflammatory gene expression in sheep exposed to heat stress.

The objective of this study was to investigate the effects of chronic heat (thermal) stress and dietary antioxidant supplementation on the expression of heat shock proteins and inflammatory genes in the skeletal muscle of sheep. Twenty-four Merino × Poll Dorset crossbred ewes were allocated to either a control (10 IU vitamin E and 0.24 mg Se/kg DM) or high-antioxidant (VitE+Se; 100 IU vitamin E and 1.20 mg Se/kg DM) diet and were exposed to 2 thermal (temperature) treatments (thermoneutral [TN]: 18°C-21°C and 26%-30% relative humidity; heat stress [HS]: 28°C-40°C and 40%-50% relative humidity) for 1 wk. Physiological parameters were recorded daily, and muscle biopsies were conducted at the end of thermal treatments. Total RNA was extracted from muscle samples and reverse transcribed to cDNA for real-time PCR analysis. Respiration rates and rectal temperature were increased in response to HS (84.2 vs. 161 breaths per minute and 39.52°C vs. 40.06°C for TN and HS conditions, respectively; P < 0.001). There were interactions between dietary and thermal treatments, indicating that dietary antioxidant supplementation reduced respiration rate (P = 0.097) and rectal temperature (P = 0.086) of sheep during HS but not TN conditions. Skeletal muscle heat shock transcription factor 1 (HSF1) mRNA abundance was increased by HS (1.3-fold; P < 0.050) but was not changed (P = 0.77) by dietary antioxidant supplementation. The expression of skeletal muscle heat shock protein 70 (HSP70) mRNA was increased (P < 0.001) 3.5-fold by HS and tended (P = 0.08) to be increased by dietary antioxidant supplementation. Although there were no main effects of diet (P = 0.42) or HS (P = 0.47) on skeletal muscle HSP90 mRNA expression, there was an interaction (P = 0.040) such that HSP90 mRNA expression was increased (P = 0.010) in antioxidant-supplemented sheep under HS compared to TN conditions. Skeletal muscle nuclear factor kappa B (NF-κB) and tissue necrosis factor α (TNF-α) mRNA abundances were increased by exposure to heat (5.2-fold, P = 0.005 for NF-κB; 5.7-fold, P = 0.013 for TNF-α) ,but there was no main effect (P > 0.05) of dietary antioxidant supplementation. There was, however, an interaction between thermal and dietary treatments such that dietary antioxidant supplementation ameliorated the effect of HS on NF-κB and TNF-α mRNA expression. Taken together, these results indicate that high dietary antioxidants modulate skeletal muscle expression of heat shock proteins, proinflammatory cytokine, and NF-κB transcription, which may protect against HS in sheep.

Skeletal muscle heat shock protein 70: diverse functions and therapeutic potential for wasting disorders

The stress-inducible 70-kDa heat shock protein (HSP70) is a highly conserved protein with diverse intracellular and extracellular functions. In skeletal muscle, HSP70 is rapidly induced in response to both non-damaging and damaging stress stimuli including exercise and acute muscle injuries. This upregulation of HSP70 contributes to the maintenance of muscle fiber integrity and facilitates muscle regeneration and recovery. Conversely, HSP70 expression is decreased during muscle inactivity and aging, and evidence supports the loss of HSP70 as a key mechanism which may drive muscle atrophy, contractile dysfunction and reduced regenerative capacity associated with these conditions. To date, the therapeutic benefit of HSP70 upregulation in skeletal muscle has been established in rodent models of muscle injury, muscle atrophy, modified muscle use, aging, and muscular dystrophy, which highlights HSP70 as a key therapeutic target for the treatment of various conditions which negatively affect skeletal muscle mass and function. This article will review these important findings and provide perspective on the unanswered questions related to HSP70 and skeletal muscle plasticity which require further investigation.

The Exercise-Induced Stress Response of Skeletal Muscle, with Specific Emphasis on Humans

Skeletal muscle adapts to the stress of contractile activity via changes in gene expression to yield an increased content of a family of highly conserved cytoprotective proteins known as heat shock proteins (HSPs). These proteins function to maintain homeostasis, facilitate repair from injury and provide protection against future insults. The study of the exercise-induced production of HSPs in skeletal muscle is important for the exercise scientist as it may provide a valuable insight into the molecular mechanisms by which regular exercise can provide increased protection against related and non-related stressors. As molecular chaperones, HSPs are also fundamental in facilitating the cellular remodelling processes inherent to the training response. Whilst the exercise-induced stress response of rodent skeletal muscle is relatively well characterized, data from humans are more infrequent and less insightful. Data indicate that acute endurance- and resistance-type exercise protocols increase the muscle content of ubiquitin, alphaB-crystallin, HSP27, HSP60, HSC70 and HSP70. Although increased HSP transcription occurs during exercise, immediately post-exercise or several hours following exercise, time-course studies using western blotting techniques have typically demonstrated a significant increase in protein content is only detectable within 1-2 days following the exercise stress. However, comparison amongst studies is complicated by variations in exercise protocol (mode, intensity, duration, damaging, non-damaging), muscle group examined, predominant HSP measured and, perhaps most importantly, differences in subject characteristics both within and between studies (training status, recent activity levels, nutritional status, age, sex, etc.). Following 'non-damaging' endurance-type activities (exercise that induces no overt structural and functional damage to the muscle), the stress response is thought to be mediated by redox signalling (transient and reversible oxidation of muscle proteins) as opposed to increases in contracting muscle temperature per se. Following 'damaging' forms of exercise (exercise that induces overt structural and functional damage to the muscle), the stress response is likely initiated by mechanical damage to protein structure and further augmented by the secondary damage associated with inflammatory processes occurring several days following the initial insult. Exercise training induces an increase in baseline HSP levels, which is dependent on a sustained and currently unknown dose of training and also on the individual's initial training status. Furthermore, trained subjects display an attenuated or abolished stress response to customary exercise challenges, likely due to adaptations of baseline HSP levels and the antioxidant system. Whilst further fundamental work is needed to accurately characterize the exercise-induced stress response in specific populations following varying exercise protocols, exercise scientists should also focus their efforts on elucidating the precise biological significance of the exercise-induced induction of HSPs. In addition to their potential cytoprotective properties, the role of HSPs in modulating cell signalling pathways related to both exercise adaptation and health and disease also needs further investigation. As a non-pharmacological intervention, exercise and the associated up-regulation of HSPs and the possible correction of maladapted pathways may therefore prove effective in providing protection against protein misfolding diseases and in preserving muscle function during aging.

Heat shock proteins and exercise: a primer

Heat shock proteins (HSPs) are, in general, prosurvival molecules within the cellular environment, and the overexpression of even just 1 family of HSPs can lead to protection against and improvements after a variety of stressors. Not surprisingly, a fertile area of study has grown out of efforts to exploit the innate biologic behaviour of HSPs. Exercise, because of the inherent physiologic stresses associated with it, is but 1 stimulus that can result in a robust increase in various HSPs in several tissues, not the least of which happen to be the heart and skeletal muscle. The purpose of this review is to introduce the reader to the major HSP families, the control of their expression, and some of their biologic functions, specifically with respect to the influence of exercise. Moreover, as the first in a series of reviews from a common symposium, we will briefly introduce the concepts presented by the other authors, which include the effects of different exercise paradigms on skeletal muscle HSPs in the adult and aged systems, HSPs as regulators of inflammation, and the ion channel stabilizing effects of HSPs.

Gender differences in skeletal muscle heat shock proteins induced by diathermy

Heat shock treatments have been used to appreciably increase heat shock protein 70 (Hsp70) and phosphorylation of heat shock protein 27 (Hsp27p). These proteins are believed to be involved in the repair process of myofibrils. The purpose of this investigation was to determine whether diathermy can increase Hsp70 and Hsp27p content in skeletal muscle. Fourteen subjects (n= 7 / group, 18–35 y) received a muscle biopsy from the v. lateralis and then underwent 20 min of diathermy followed by 20 min of hot pack heating on the contralateral leg. Twenty-four hours following treatment, a second muscle biopsy was performed on the treated leg. All samples were analyzed for Hsp70 content using western immunoblotting. Images of the blots were obtained and analyzed via densitometry. A paired t-Test was used to examine differences in heat shock protein content between the treated and untreated legs. Significance was set at P<0.05. Twenty-four hours following the heat treatment, female subjects significantly increased Hsp70 (58%) and Hsp27-p (132%) content compared to the untreated leg. Male subjects had non-significant increases in Hsp70 (35%) and Hsp27-p (68%) skeletal muscle content. These results implicate diathermy as an effective countermeasure to induce Hsp70 & Hsp27-p in female populations. Supported, in part, by a University of Kansas General Research Fund grant (P. Gallagher), and a McNair Scholarship (T. Le).

Alcohol alters skeletal muscle heat shock protein gene expression in rats: these effects are moderated by sex, raised endogenous acetaldehyde, and starvation

Alcoholic myopathy is a common pathology characterized by wasting due to reduced protein synthesis, although the mechanisms involved remain unclear. Women are particularly sensitive and malnutrition exacerbates the myopathy. This study aimed to address (i) whether long-term alcohol feeding alters expression of heat shock proteins (HSPs) in male and female rats; (ii) the effect of immediate alcohol dosing with or without raised levels of endogenous acetaldehyde; and (iii) the effect of starvation. To address this, (i) male and female rats were fed alcohol in the long-term (6-7 weeks as 35% of energy in a liquid diet) and compared to controls fed the same diet with isoenergetic glucose; (ii) male rats given an immediate bolus (75 mmol ethanol per kilogram body weight intraperitoneally) 2.5 hours before sacrifice and compared to controls given a dose of saline (with or without pretreatment with cyanamide—an acetaldehyde dehydrogenase inhibitor which raises endogenous acetaldehyde); (iii) male rats starved for 1 or 2 days then immediately dosed with alcohol. Protein levels of HSP 27, HSP 60, and HSP 70 were measured in muscles of male rats fed alcohol and pair-fed control rats by SDS-PAGE and Western blotting in study I. Levels of HSP 27, HSP 60, HSP 70, and HSP 90 mRNA were analyzed in hind limb skeletal muscle by reverse transcription–polymerase chain reaction with an endogenous internal standard, glyceraldehyde-3-phosphate-dehydrogenase. (i) Long-term alcohol dosage reduced HSP 27 in male rats but not in females, whereas HSP 90 mRNA increased in long-term alcohol-fed female rats but not in male rats. These changes were reflected by a similar trend in HSP protein content, although statistical significance was not achieved. (ii) There was no effect on any of the HSP mRNAs in rats dosed immediately with alcohol or in combination with cyanamide. (iii) Starvation per se for 2 days was associated with an increase in HSP 27 mRNA. Alcohol administration after 2 days starvation caused a blunting of the increased HSP 27 mRNA in starvation alone. This suggests that long-term alcohol exposure affects HSP gene expression and that this effect is moderated by sex and starvation. This may contribute to, or reflect, the biochemical lesion in alcoholic myopathy.

Response and function of skeletal muscle heat shock protein 70

In response to stress, cells produce a series of heat shock proteins (Hsps). One of the most prominent Hsps, is the 70 kDa Hsp (Hsp70). Hsp70 is a highly conserved and essential protein against stress. The skeletal muscle responds to a diverse group of stress signals namely, muscle contraction linked energy and milieu challenges, ischemia and exercise by producing Hsp70. The extent of this Hsp70 response in skeletal muscle depends on the type and intensity of the signal, and is characterized in a muscle fiber specific manner by a special time course. Hsp70 in the skeletal muscle is regulated at transcriptional, translational and posttranslational levels. Hsp70 serves as an indicator for cellular stress as a molecular chaperone, plays pivotal role in maintaining cellular homeostasis by preventing apoptosis, influences energy metabolism, facilitates cellular processes in terms of muscular adaptation and interacts with other signalling pathways. This review summarizes our current knowledge on the skeletal muscle Hsp70 response.

Skeletal muscle HSP72 and norepinephrine response to static magnetic field in rat

The present work was undertaken in order to investigate the noradrenergic system and skeletal muscle heat shock protein 72 (HSP72) response to static magnetic field (MF) in male rats. At thermoneutrality (25 degrees C), the exposition of rats 1 hour/day for 5 consecutive days to MF of 128 mT (m tesla) induced an increase in norepinephrine content in gastrocnemius muscle (+25%, p < 0.05) but had no effect at 67 mT (+1%, p > 0.05), indicating a stimulatory effect of sub-acute MF exposure on the noradrenergic system activity. Moreover, exposed rats to MF displayed a non-significant increase of HSP72 levels in gastrocnemius muscles (+29%, p > 0.05). The results indicate that noradrenergic systems in rat's gastrocnemius muscles are affected by MF exposure. Interestingly, sub-acute exposure insufficiency increased HSP72 levels in gastrocnemius muscles.

The Effects of Eccentric Contraction Preconditioning on Ischemia- Reperfusion Injury in Mouse Skeletal Muscle

2013 Endurance exercise-induced increase in cardiac heat shock protein (HSP) is associated with reductions in ischemia-reperfusion (I-R) injury in the heart. Eccentrically biased exercise is associated with increases in skeletal muscle HSP and protection from exercise-induced muscle injury in subsequent bouts. PURPOSE: To ascertain whether preconditioning of mouse anterior crural muscle with eccentric contractions protects the muscle against I-R injury. The left anterior crural muscles of mice performed either 150 passive concentric or 150 eccentric contractions in vivo. METHODS: I-R injury was induced 2 wks later by placing a tourniquet around the left upper thigh for 2 h. Peak isometric torque as a function of stimulation frequency (20–400 Hz) was measured immediately before and after the preconditioning exercise and I-R injury, and at 7, 14 and 21 d after ischemia. At 21 d, the injured and contralateral control EDL muscles were dissected free for in vitro contractile measurements. RESULTS: Peak isometric torques (20–400 Hz) were decreased immediately (91–52%) after eccentric contraction-induced injury. Immediately prior to I-R injury there were no differences between groups for peak isometric torques at frequencies (20–400 Hz). I-R injury resulted in significant, and similar, reductions in peak isometric torques in both groups immediately after injury (99–100%), and at 7 d (84–90%), 14 d (40–48%) and 21 d (30–35%). There were no differences between groups for peak isometric twitch and tetanic forces, specific force, and wet weight for injured EDL muscles 21 d after I-R injury. CONCLUSION: Preconditioning mouse skeletal muscle with a single bout of eccentric contractions does not appear to protect the muscle against I-R injury.

The Effects of Eccentric Contraction Preconditioning on Ischemia- Reperfusion Injury in Mouse Skeletal Muscle

2013 Endurance exercise-induced increase in cardiac heat shock protein (HSP) is associated with reductions in ischemia-reperfusion (I-R) injury in the heart. Eccentrically biased exercise is associated with increases in skeletal muscle HSP and protection from exercise-induced muscle injury in subsequent bouts. PURPOSE: To ascertain whether preconditioning of mouse anterior crural muscle with eccentric contractions protects the muscle against I-R injury. The left anterior crural muscles of mice performed either 150 passive concentric or 150 eccentric contractions in vivo. METHODS: I-R injury was induced 2 wks later by placing a tourniquet around the left upper thigh for 2 h. Peak isometric torque as a function of stimulation frequency (20–400 Hz) was measured immediately before and after the preconditioning exercise and I-R injury, and at 7, 14 and 21 d after ischemia. At 21 d, the injured and contralateral control EDL muscles were dissected free for in vitro contractile measurements. RESULTS: Peak isometric torques (20–400 Hz) were decreased immediately (91–52%) after eccentric contraction-induced injury. Immediately prior to I-R injury there were no differences between groups for peak isometric torques at frequencies (20–400 Hz). I-R injury resulted in significant, and similar, reductions in peak isometric torques in both groups immediately after injury (99–100%), and at 7 d (84–90%), 14 d (40–48%) and 21 d (30–35%). There were no differences between groups for peak isometric twitch and tetanic forces, specific force, and wet weight for injured EDL muscles 21 d after I-R injury. CONCLUSION: Preconditioning mouse skeletal muscle with a single bout of eccentric contractions does not appear to protect the muscle against I-R injury.

Exercise training increases heat shock protein in skeletal muscles of old rats.

The effects of chronic exercise training on the expression of heat shock protein (HSP) in skeletal muscle of senescent animals are unknown. Therefore, the purpose of this study was to investigate the effects of chronic exercise training on skeletal muscle HSP expression in both young and old rats. Young adult (3 months) and old (23 months) female Fisher 344 rats were assigned to either a sedentary control or an endurance exercise trained group (N = 6 per group). Exercised animals ran (60 min.d-1, 5 d.wk-1) on a treadmill at approximately 77% VO2peak for 10 wk. After completion of the training program, the soleus (SOL), plantaris (PL), and the red (RG) and white portions (WG) of the gastrocnemius muscles were excised, and citrate synthase (CS) activity and the relative levels of HSP72 were determined. Training resulted in increases (P < 0.05) in VO2peak in both young (67.6 +/- 3.1 vs 86.9 +/- 1.6 mL.kg-1.min-1) and old animals (54.5 +/- 1.8 vs 68.2 +/- 2.2 mL.kg-1.min-1). Training increased CS activity and the relative levels of HSP72 (P < 0.05) in all four skeletal muscles in both young and old animals. Specifically, compared with age-matched sedentary controls, exercise training resulted in increased (P < 0.05) levels of HSP72 in skeletal muscles of both young (SOL + 22%, PL +94%, RG + 44%, WG + 243%) and old animals (SOL +15%, PL +73%, RG +38%, WG +150%). These findings reveal that the exercise-induced accumulation of HSP72 in skeletal muscle differs between fast and slow muscles. Further, these data indicate that the exercise-induced accumulation of HSP72 in highly oxidative skeletal muscles (SOL and RG) is similar between young and old animals. In contrast, aging is associated with a blunted expression of HSP72 in fast skeletal muscles (PL and WG) in response to chronic exercise.

Changes in skeletal muscle heat shock proteins: pathological significance.

In response to stress, cells rapidly produce a series of new proteins known as heat shock proteins (HSP). HSPs are considered to be molecular chaperones which play a universal role in maintaining cellular homeostasis. It is known that different HSPs are expressed in skeletal muscle, namely, small HSPs (including ubiquitin, alpha B- crystallin, HSP20 and HSP 27), HSP70, HSP60 and HSP90. Skeletal muscle is a complex and heterogeneous system in that its contractile proteins are made of different isoforms to form various muscle fibre types, and each type of muscle fibre has its own histochemical and functional characteristics. It seems that the induction of HSPs differs with muscle fibre type suggesting HSP expression is muscle fibre type specific. HSPs have been shown to respond in muscle diseases and following exercise. However, the molecular mechanisms of HSP induction, regulation and its role in maintaining the muscle function, are not completely understood. Relatively few studies of HSP have been conducted in human skeletal muscles. This review discusses the significance of changes of HSPs in skeletal muscle in both physiological and pathological conditions.

Changes in skeletal muscle heat shock proteins Pathological significance

Changes in skeletal muscle heat shock proteins Pathological significance