Decreased induction of heat‐shock proteins with age in ischemia‐reperfusion injured skeletal muscle

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’.

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Short-term exercise training can improve myocardial tolerance to I/R without elevation in heat shock proteins

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.3.h1346 ◽

2001 ◽

Vol 281 (3) ◽

pp. H1346-H1352 ◽

Cited By ~ 105

Author(s):

Karyn L. Hamilton ◽

Scott K. Powers ◽

Takao Sugiura ◽

Sunjoo Kim ◽

Shannon Lennon ◽

...

Keyword(s):

Lipid Peroxidation ◽

Heat Shock ◽

Heat Shock Proteins ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Antioxidant Defenses ◽

Control Group ◽

Shock Proteins ◽

Mnsod Activity ◽

Over Time

We examined the effects of 3 days of exercise in a cold environment on the expression of left ventricular (LV) heat shock proteins (HSPs) and contractile performance during in vivo ischemia-reperfusion (I/R). Sprague-Dawley rats were divided into the following three groups ( n = 12/group): 1) control, 2) exercise (60 min/day) at 4°C (E-Cold), and 3) exercise (60 min/day) at 25°C (E-Warm). Left anterior descending coronary occlusion was maintained for 20 min, followed by 30 min of reperfusion. Compared with the control group, both the E-Cold and E-Warm groups maintained higher ( P < 0.05) LV developed pressure, first derivative of pressure development over time (+dP/d t), and pressure relaxation over time (−dP/d t) throughout I/R. Relative levels of HSP90, HSP72, and HSP40 were higher ( P < 0.05) in E-Warm animals compared with both control and E-Cold. HSP10, HSP60, and HSP73 did not differ between groups. Exercise increased manganese superoxide dismutase (MnSOD) activity in both E-Warm and E-Cold hearts ( P < 0.05). Protection against I/R-induced lipid peroxidation in the LV paralleled the increase in MnSOD activity whereas lower levels of lipid peroxidation were observed in both E-Warm and E-Cold groups compared with control. We conclude that exercise-induced myocardial protection against a moderate duration I/R insult is not dependent on increases in myocardial HSPs. We postulate that exercise-associated cardioprotection may depend, in part, on increases in myocardial antioxidant defenses.

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Preservation of skeletal muscle by the heat shock proteins following frostbite injury

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.1200.1 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Ruben Mestril ◽

Colin Schweigert ◽

Jason Batey ◽

Tomas Liskutin ◽

John Baldwin

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Shock Proteins

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Abstract 340: Heat Shock Proteins HSP90 and HSP70 Mediate Opioid- and GSK3β-induced Cardioprotection

Circulation Research ◽

10.1161/res.115.suppl_1.340 ◽

2014 ◽

Vol 115 (suppl_1) ◽

Author(s):

Sarah K Jimenez ◽

Bryce A Small ◽

Anna K Hsu ◽

Garrett J Gross ◽

Eric R Gross

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Infarct Size ◽

Glycogen Synthase ◽

Ischemia Reperfusion ◽

Myocardial Salvage ◽

Sequence Motif ◽

Protein Partners ◽

Gsk 3Β ◽

Shock Proteins

Previously, opioids were established to reduce myocardial injury in an ischemic preconditioning (IPC)-like manner, involving a central and downstream role of glycogen synthase kinase-3 beta (GSK-3β) inhibition. However, the mechanism of GSK-3β inhibition mediating cardioprotection and the protein partners involved has not been fully elucidated. Hence, we used a non-biased sequence scan of the proteome to determine potential GSK-3β protein partners and tested whether two candidate proteins, heat shock proteins (HSP) 70 and 90, are involved in the mechanism of opioid-induced cardioprotection. A non-biased BLAST search was performed for putative GSK-3β target substrates, based upon the sequence motif S/T-X-X-X-S/T. Approximately 700 proteins were identified to have this moiety, including many of the HSP protein class, including HSP70 and HSP90. To determine whether HSP70 or HSP90 are indeed important in opioid-induced cardioprotection, rats were subjected to an in vivo myocardial ischemia-reperfusion protocol consisting of 30 minutes of ischemia and 2 hours of reperfusion of the left anterior descending coronary artery followed by infarct size assessment. Either morphine (0.3mg/kg) or inhibition of GSK-3β using SB216763 (0.6mg/kg), reduced infarct size compared to control (42.21±1*% and 41.09±2*%, respectively versus control 60.38±1.2, *P<0.01). Inhibition of HSP70 using desoxysperguanalin (DSG), or HSP90 using radicicol (RAD), abrogated morphine-induced protection (56.09±2 and 58.64±1, respectively). Either DSG or RAD partially inhibited protection in the presence of GSK-3β (47.28±1.071 and 49.88±3.09). Our results suggest that morphine-induced cardioprotection occurs by a HSP70 and HSP90- dependent mechanism, with this HSP machinery partially required for GSK3β-inhibition-induced cardioprotection. Further understanding of this mechanism is important, considering many agents targeting HSP are currently in development as novel cancer treatments, which may have detrimental effects on the myocardial salvage mediated by opioids or by GSK3β-inhibition.

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Role of Heat Shock Proteins in Skeletal Muscle

Skeletal Muscle - From Myogenesis to Clinical Relations ◽

10.5772/47815 ◽

2012 ◽

Author(s):

Thiago Gomes ◽

Sofia Pizzato ◽

Mirna Stela ◽

Paulo Ivo Homem de Bittencourt Jr.

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Shock Proteins

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Potential Cytoprotective Effects of Heat Shock Proteins to Skeletal Muscle

Heat Shock Proteins - Heat Shock Protein-Based Therapies ◽

10.1007/978-3-319-17211-8_7 ◽

2015 ◽

pp. 119-127 ◽

Cited By ~ 1

Author(s):

John P. Vardiman ◽

Philip M. Gallagher ◽

Jacob A. Siedlik

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Shock Proteins

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Changes in skeletal muscle heat shock proteins: Pathological significance

Frontiers in Bioscience ◽

10.2741/liu ◽

2001 ◽

Vol 6 (1) ◽

pp. d12 ◽

Cited By ~ 45

Author(s):

Yuefei Liu

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Shock Proteins

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Protective role of TAT-HSP70 after myocardial I/R injury

American Journal of BioMedicine ◽

10.18081/2333-5106/015-04/289-294 ◽

2017 ◽

Vol 5 (3) ◽

pp. 279-284

Author(s):

Martin A. Meenakshi ◽

Erik G. Seth

Keyword(s):

Heat Shock ◽

Heat Shock Proteins ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Protective Role ◽

Inflammatory Mechanism ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion ◽

Shock Proteins

Myocardial ischemia reperfusion injury I/R adversely affects cardiac function. Heat shock proteins (HSPs) are a highly conserved family of proteins with diverse functions expressed by all cells exposed to environmental stress including myocardila injury. We investigated release of small constitutive heat shock proteins (HSPs) from mouse myocardium and the effects of TAT-HSP70 after myocardial I/R via occluding the left coronary artery (LAD). The results support the hypothesis that elevated HSPs in myocardium after ischemia and reperfusion and contributes to the inflammatory mechanism of myocardial functional injury. Further investigation of the significance of HSPs accumulation to the evolution of myocardial injury.

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Heat shock proteins and exercise: a primer

Applied Physiology Nutrition and Metabolism ◽

10.1139/h08-069 ◽

2008 ◽

Vol 33 (5) ◽

pp. 1050-1075 ◽

Cited By ~ 91

Author(s):

Earl G. Noble ◽

Kevin J. Milne ◽

C.W. James Melling

Keyword(s):

Skeletal Muscle ◽

Heat Shock ◽

Heat Shock Proteins ◽

Ion Channel ◽

The Other ◽

Cellular Environment ◽

Shock Proteins ◽

Fertile Area ◽

Area Of Study

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 effors 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.

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