Castration inhibits exercise-induced accumulation of Hsp70 in male rodent hearts

2006 ◽  
Vol 290 (4) ◽  
pp. H1610-H1616 ◽  
Author(s):  
K. J. Milne ◽  
D. B. Thorp ◽  
C. W. J. Melling ◽  
E. G. Noble
Keyword(s):  
Heat Shock ◽  
Acute Exercise ◽  
Exercise Bout ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Intact Male ◽  
Hsp70 Mrna ◽  
Male Response ◽  
Exercise Induced ◽  
Shock Proteins

Intense exercise leads to accumulation of the inducible member of the 70-kDa family of heat shock proteins, Hsp70, in male, but not female, hearts. Estrogen is at least partially responsible for this difference. Because androgen receptors are expressed in the heart and castration leads to decreases in calcium regulatory proteins and altered cardiac function, testosterone (T) or its metabolites could also be involved. We hypothesized that removal of endogenous T production through castration would reduce cardiac Hsp70 accumulation after an acute exercise bout, whereas castrated animals supplemented with 5α-dihydrotestosterone (DHT) would show the intact male response. Fifty-four 8-wk-old male Sprague-Dawley rats were divided into intact, castrated, or castrated + DHT groups ( n = 18/group). At 11 wk of age, 12 animals in each group undertook a 60-min bout of treadmill running at 30 m/min (2% incline) while the remaining 6 in each group remained sedentary. At 30 min or 24 h after exercise ( n = 6/time point), blood and hearts were harvested for analysis. Serum T was undetectable in castrated and DHT-treated castrated rats, whereas serum DHT was significantly reduced in castrated animals only (∼60% reduction) ( P < 0.05). Although there were no differences in constitutive levels of Hsp70 protein, exercise significantly increased cardiac hsp70 mRNA and protein in intact and DHT-supplemented rats, but not in castrated animals ( P < 0.05). To examine whether castration eliminated the ability to respond to stress, another six intact and six castrated animals were subjected to a 15-min period of hyperthermia (core temperature raised to 42°C) and killed 24 h later. As opposed to exercise, castrated animals subjected to heat shock exhibited increases in Hsp70 above nonshocked (i.e., sedentary) animals, similarly to intact males ( P < 0.05). These data suggest that androgens, in addition to estrogen, play a role in the sexual dimorphism observed in the stress response to exercise but not heat shock.

scholarly journals Myocardial accumulation and localization of the inducible 70-kDa heat shock protein, Hsp70, following exercise

2012 ◽  
Vol 113 (6) ◽  
pp. 853-860 ◽  
Author(s):  
K. J. Milne ◽  
S. Wolff ◽  
E. G. Noble
Keyword(s):  
Smooth Muscle ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Acute Exercise ◽  
Exercise Bout ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Immunofluorescent Analysis ◽  
Heat Shock Protein Hsp70 ◽  
Exercise Induced

Exercise increases the 70-kDa heat shock protein (Hsp70) in the myocardium, and this exercise-induced increase is associated with significantly improved cardiac recovery following insult. However, while heat shock has been shown to elevate Hsp70 primarily in the cardiac vasculature of the myocardium, the localization following exercise is unknown. Male Sprague-Dawley rats performed continuous treadmill running at 30 m/min for 60 min (2% incline) on either 1 or 5 consecutive days. At 30 min and 24 h following exercise, hearts were extirpated, and the left ventricle was isolated, OCT-cork mounted, and sectioned for immunofluorescent analysis. Whereas immunofluorescent analysis revealed little to no Hsp70 in control hearts and 30 min postexercise, the accumulation of Hsp70 24 h after a single exercise bout or 5 days of training was predominantly located in large blood vessels and, in particular, colocalized with a marker of smooth muscle. Furthermore, higher core temperatures attained during exercise led to more abundant accumulation in smaller vessels and the endothelium. It is concluded that the accumulation of myocardial Hsp70 following acute exercise predominantly occurs in a cell type-specific manner, such that changes in the cardiac vasculature account for much of the increase. This accumulation appears first in the smooth muscle of larger vessels and then increases in smaller vessels and the endothelium, as core temperature attained during exercise increases. This finding supports the observations after heat shock and further suggests that the vasculature is a primary target in exercise-induced cardioprotection.

scholarly journals Heat shock proteins and exercise adaptations. Our knowledge thus far and the road still ahead

2016 ◽  
Vol 120 (6) ◽  
pp. 683-691 ◽  
Author(s):  
Darren C. Henstridge ◽  
Mark A. Febbraio ◽  
Mark Hargreaves
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Acute Exercise ◽  
Exercise Physiology ◽  
Protective Role ◽  
Protective Mechanisms ◽  
The Road ◽  
Exercise Activity ◽  
Exercise Induced ◽  
Shock Proteins

By its very nature, exercise exerts a challenge to the body's cellular homeostatic mechanisms. This homeostatic challenge affects not only the contracting skeletal muscle but also a number of other organs and results over time in exercise-induced adaptations. Thus it is no surprise that heat shock proteins (HSPs), a group of ancient and highly conserved cytoprotective proteins critical in the maintenance of protein and cellular homeostasis, have been implicated in exercise/activity-induced adaptations. It has become evident that HSPs such as HSP72 are induced or activated with acute exercise or after chronic exercise training regimens. These observations have given scientists an insight into the protective mechanisms of these proteins and provided an opportunity to exploit their protective role to improve health and physical performance. Although our knowledge in this area of physiology has improved dramatically, many questions still remain unanswered. Further understanding of the role of HSPs in exercise physiology may prove beneficial for therapeutic targeting in diseased patient cohorts, exercise prescription for disease prevention, and training strategies for elite athletes.

Activation of heat-shock transcription factor in rat heart after heat shock and exercise

1995 ◽  
Vol 268 (6) ◽  
pp. C1387-C1394 ◽  
Author(s):  
M. Locke ◽  
E. G. Noble ◽  
R. M. Tanguay ◽  
M. R. Feild ◽  
S. E. Ianuzzo ◽  
...  
Keyword(s):  
Heat Shock ◽  
Cultured Cells ◽  
Treadmill Running ◽  
Rat Myocardium ◽  
Sprague Dawley ◽  
Mobility Shift ◽  
Heat Shock Element ◽  
Heat Shock Transcription Factors ◽  
Sprague Dawley Rats ◽  
Shock Proteins

Stress-induced transcriptional regulation of the heat-shock proteins (HSP) is mediated by activation and binding of the heat-shock transcription factors (HSF) to the heat-shock element (HSE). Given the similarities between the stressors known to activate the HSF in cultured cells and the physiological stresses known to occur during exercise, HSF activation was examined in the hearts from exercising animals. Sprague-Dawley rats (5 rats/group) were run on a treadmill (24 m/min) for either 0, 20, 40, or 60 min or to exhaustion (102 +/- 7 min). Protein extracts were assessed for HSF activation by mobility-shift gels. Extracts from the hearts of nonrunning rats demonstrated no HSF activation, whereas HSF activation was detected in 80% of the hearts from animals that run for at least 40 min. These results demonstrate that treadmill running is capable of activating the HSF and increasing 70-kDa HSP mRNA in the rat myocardium.

Does β3-adrenoreceptor blockade attenuate acute exercise-induced reductions in leptin mRNA?

1999 ◽  
Vol 87 (5) ◽  
pp. 1678-1683 ◽  
Author(s):  
S. Brooke Bramlett ◽  
Jun Zhou ◽  
Ruth B. S. Harris ◽  
Stephen L. Hendry ◽  
Trudy L. Witt ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Acute Exercise ◽  
Liver Glycogen ◽  
Treadmill Running ◽  
Control Group ◽  
Mrna Levels ◽  
Sprague Dawley ◽  
Receptor Stimulation ◽  
Exercise Induced

We investigated the effect of a single bout of exercise on leptin mRNA levels in rat white adipose tissue. Male Sprague-Dawley rats were randomly assigned to an exercise or control group. Acute exercise was performed on a rodent treadmill and was carried out to exhaustion, lasting an average of 85.5 ± 1.5 min. At the end of exercise, soleus muscle and liver glycogen were reduced by 88% ( P < 0.001). Acutely exercised animals had lower ( P< 0.05) leptin mRNA levels in retroperitoneal but not epididymal fat, and this was independent of fat pad weight. To test the hypothesis that β3-adrenergic-receptor stimulation was involved in the downregulation of leptin mRNA in retroperitoneal fat, a second experiment was performed in which rats were randomized into one of four groups: control, control + β3-antagonist, exercise, and exercise + β3-antagonist. A highly selective β3-antagonist (SR-59230A) or vehicle was given by gavage 30 min before exercise or control experiment. Exercise consisted of 55 min of treadmill running, sufficient to reduce liver and muscle glycogen by 70 and 80%, respectively (both P < 0.0001). Again, acute exercise reduced leptin mRNA in retroperitoneal fat (exercise vs. control; P < 0.05), but β3-antagonism blocked this effect (exercise + β3-antagonist vs. control + β3-antagonist; P = 0.42). Unexpectedly, exercise increased serum leptin. This would be consistent with the idea that there are releasable, preformed pools of leptin within adipocytes. We conclude that β3-receptor stimulation is a mechanism by which acute exercise downregulates retroperitoneal adipose tissue leptin mRNA in vivo.

Acute exercise increases nitric oxide synthase activity in skeletal muscle

1999 ◽  
Vol 277 (2) ◽  
pp. E390-E394 ◽  
Author(s):  
Christian K. Roberts ◽  
R. James Barnard ◽  
Arnie Jasman ◽  
Thomas W. Balon
Keyword(s):  
Nitric Oxide ◽  
Skeletal Muscle ◽  
Nitric Oxide Synthase ◽  
Acute Exercise ◽  
Exercise Bout ◽  
Treadmill Running ◽  
Sprague Dawley ◽  
Glycogen Depletion ◽  
Neuronal Nos ◽  
Oxide Synthase

This study examined the effects of acute exercise on skeletal muscle nitric oxide synthase (NOS) activity. Female Sprague-Dawley rats were divided into three groups: control, exercise, and exercise + N G-nitro-l-arginine methyl ester (l-NAME). In the exercise + l-NAME group, l-NAME was administered in the drinking water (1 mg/ml) for 2 days and subsequently the exercise and exercise + l-NAME groups underwent a 45-min bout of exhaustive treadmill running after which NOS activity and muscle glycogen were measured. In the control and exercise groups, 1-amino- S-methylisothiourea (AMITU), a selective neuronal NOS inhibitor, with and without additional nonselective NOS blockade [with N G-monomethyl-l-arginine (l-NMMA)], was used in vitro to assess the contribution of nNOS to total NOS activity. The exercise bout increased NOS activity by 37% in exercise compared with control groups, and both groups had significantly greater NOS activity compared with exercise + l-NAME. AMITU decreased total NOS activity in the control and exercise groups by 31.8 and 30.2%, respectively, and these activities were significantly greater than AMITU +l-NMMA in both control and exercise groups. We conclude that 1) there is basal neuronal NOS and endothelial NOS activity in skeletal muscle, 2) an acute exercise bout increases NOS activity in skeletal muscle, and 3) glycogen depletion during exercise occurs irrespective of NOS activity.

scholarly journals Immediate effects of a single exercise bout on protein O-GlcNAcylation and chromatin regulation of cardiac hypertrophy

2013 ◽  
Vol 305 (1) ◽  
pp. H114-H123 ◽  
Author(s):  
Heidi M. Medford ◽  
Karen Porter ◽  
Susan A. Marsh
Keyword(s):  
Cardiac Hypertrophy ◽  
Histone Deacetylases ◽  
Acute Exercise ◽  
Exercise Bout ◽  
Treadmill Running ◽  
Hypertrophic Signaling ◽  
Intracellular Changes ◽  
Exercise Induced ◽  
Nuclear Levels ◽  
Glcnac Transferase

Cardiac hypertrophy induced by pathological stimuli is regulated by a complex formed by the repressor element 1-silencing transcription factor (REST) and its corepressor mSin3A. We previously reported that hypertrophic signaling is blunted by O-linked attachment of β- N-acetylglucosamine ( O-GlcNAc) to proteins. Regular exercise induces a physiological hypertrophic phenotype in the heart that is associated with decreased O-GlcNAc levels, but a link between O-GlcNAc, the REST complex, and initiation of exercise-induced cardiac hypertrophy is not known. Therefore, mice underwent a single 15- or 30-min bout of moderate- to high-intensity treadmill running, and hearts were harvested immediately and compared with sedentary controls. Cytosolic O-GlcNAc was lower ( P < 0.05) following 15 min exercise with no differences in nuclear levels ( P > 0.05). There were no differences in cytosolic or nuclear O-GlcNAc levels in hearts after 30 min exercise ( P > 0.05). Cellular compartment levels of O-GlcNAc transferase (OGT, the enzyme that removes the O-GlcNAc moiety from proteins), REST, mSin3A, and histone deacetylases (HDACs) 1, 2, 3, 4, and 5 were not changed with exercise. Immunoprecipitation revealed O-GlcNAcylation of OGT and HDACs 1, 2, 4, and 5 that was not changed with acute exercise; however, exercised hearts did exhibit lower interactions between OGT and REST ( P < 0.05) but not between OGT and mSin3A. These data suggest that hypertrophic signaling in the heart may be initiated by as little as 15 min of exercise via intracellular changes in protein O-GlcNAcylation distribution and reduced interactions between OGT and the REST chromatin repressor.

Exercise-induced elevation of HSP70 is intensity dependent

2002 ◽  
Vol 93 (2) ◽  
pp. 561-568 ◽  
Author(s):  
Kevin J. Milne ◽  
Earl G. Noble
Keyword(s):  
Exercise Intensity ◽  
Striated Muscle ◽  
Exercise Bout ◽  
Treadmill Running ◽  
Hsp70 Expression ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Muscle Loading ◽  
Recruitment Patterns ◽  
Exercise Induced

Exercise induces expression of the protective heat shock protein, HSP70, in striated muscle. To characterize the relationship between induction of this protein and exercise intensity in muscles exhibiting different recruitment patterns, male Sprague-Dawley rats were assigned to a sedentary control or one of seven exercise groups for which treadmill running speed varied between 15 and 33 m/min ( n = 8/group). Twenty-four hours after a single 60-min exercise bout, hearts, red and white portions of the vastus (RV and WV, respectively) muscles, and soleus (Sol) muscles were harvested and analyzed for both relative and absolute HSP70 content. Cardiac HSP70 was significantly elevated only when animals were exercised at 24 m/min and beyond. Similarly, HSP70 was elevated in RV at running speeds above 24 m/min but did not increase in WV until 27 m/min. In contrast, HSP70 content was initially elevated in the Sol but subsequently declined at the highest running speeds. The observed patterns of HSP70 expression in skeletal muscle were in general accordance with known muscle recruitment patterns and suggest that alterations in muscle loading, resulting from changes in exercise intensity, are an important component of exercise-induced increases in HSP70 content.

scholarly journals Acute exercise‐induced heat shock proteins do not protect heart from hypoxia‐reoxygenation injury in adult rat

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Hiroto Tsujikawa ◽  
Yuji Ogura ◽  
Ryo Kakigi ◽  
Mitsutoshi Kurosaka ◽  
Hisashi Naito ◽  
...  
Keyword(s):  
Heat Shock ◽  
Heat Shock Proteins ◽  
Acute Exercise ◽  
Adult Rat ◽  
Reoxygenation Injury ◽  
Exercise Induced ◽  
Shock Proteins ◽  
Hypoxia Reoxygenation

scholarly journals Exercise, heat shock proteins and insulin resistance

2017 ◽  
Vol 373 (1738) ◽  
pp. 20160529 ◽  
Author(s):  
Ashley E. Archer ◽  
Alex T. Von Schulze ◽  
Paige C. Geiger
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Heat Shock ◽  
Heat Shock Proteins ◽  
Metabolic Effects ◽  
Diabetic Patients ◽  
Alcoholic Fatty Liver ◽  
Insulin Resistant ◽  
Exercise Induced ◽  
Shock Proteins

Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs. This article is part of the theme issue ‘Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective’.

scholarly journals Resistance training reduces the acute exercise-induced increase in muscle protein turnover

1999 ◽  
Vol 276 (1) ◽  
pp. E118-E124 ◽  
Author(s):  
S. M. Phillips ◽  
K. D. Tipton ◽  
A. A. Ferrando ◽  
R. R. Wolfe
Keyword(s):  
Resistance Training ◽  
Resistance Exercise ◽  
Acute Exercise ◽  
Muscle Protein ◽  
Exercise Bout ◽  
Muscle Contractions ◽  
Breakdown Rates ◽  
Single Bout ◽  
Fractional Synthesis ◽  
Exercise Induced

We examined the effect of resistance training on the response of mixed muscle protein fractional synthesis (FSR) and breakdown rates (FBR) by use of primed constant infusions of [2H5]phenylalanine and [15N]phenylalanine, respectively, to an isolated bout of pleiometric resistance exercise. Trained subjects, who were performing regular resistance exercise (trained, T; n = 6), were compared with sedentary, untrained controls (untrained, UT; n = 6). The exercise test consisted of 10 sets (8 repetitions per set) of single-leg knee flexion (i.e., pleiometric muscle contraction during lowering) at 120% of the subjects’ predetermined single-leg 1 repetition maximum. Subjects exercised one leg while their contralateral leg acted as a nonexercised (resting) control. Exercise resulted in an increase, above resting, in mixed muscle FSR in both groups (UT: rest, 0.036 ± 0.002; exercise, 0.0802 ± 0.01; T: rest, 0.045 ± 0.004; exercise, 0.067 ± 0.01; all values in %/h; P< 0.01). In addition, exercise resulted in an increase in mixed muscle FBR of 37 ± 5% (rest, 0.076 ± 0.005; exercise, 0.105 ± 0.01; all values in %/h; P < 0.01) in the UT group but did not significantly affect FBR in the T group. The resulting muscle net balance (FSR − FBR) was negative throughout the protocol ( P < 0.05) but was increased in the exercised leg in both groups ( P < 0.05). We conclude that pleiometric muscle contractions induce an increase in mixed muscle protein synthetic rate within 4 h of completion of an exercise bout but that resistance training attenuates this increase. A single bout of pleiometric muscle contractions also increased the FBR of mixed muscle protein in UT but not in T subjects.

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