Hsp70 prevents disuse muscle atrophy in senescent rats

Dodd, Stephen; Hain, Brian A.; Judge, Andrew R.

doi:10.1007/s10522-008-9203-1

Cited by 29 publications

(37 citation statements)

References 30 publications

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“…HSP70 is a constitutively active, cytoprotective protein, which acts like a molecular chaperone and is elevated during cellular stress in skeletal muscle. In fact, previously published reports revealed that overexpression of HSP70 in mouse skeletal muscle protects against muscle damage and age-related muscle dysfunction (38,39). In contrast, decreased HSP70 levels have been shown to contribute to the pathogenicity of multiple models of skeletal muscle atrophy (40).…”

Section: Discussionmentioning

confidence: 99%

Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Kukreti

Kottaiswamy

Harikumar

et al. 2013

Journal of Biological Chemistry

110

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Background: miR1 is a muscle-specific microRNA, however, its role in muscle atrophy is unclear. Results: Excess dexamethasone and myostatin induced miR1 via glucocorticoid receptor, resulting in reduced HSP70 and development of muscle atrophy. Conclusion: miR1 mediates muscle atrophy by regulating the levels of HSP70. Significance: Given that miR1 has a role in muscle atrophy, its antagonism may be beneficial during atrophy.

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Section: Discussionmentioning

confidence: 99%

Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Kukreti

Kottaiswamy

Harikumar

et al. 2013

Journal of Biological Chemistry

110

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“…However, experiments with exogenously administered human recombinant HSP70 demonstrate that the protein is taken up into muscle tissue, and this results in improved muscle performance and density of innervated neuromuscular junctions (16). Additionally, increasing skeletal muscle HSPs through heat or overexpression has increased muscle mass in rat models (11,28). Our monkeys were sedentary, and it is possible that GGA-induced HSP70 in the circulation would have acted independently on peripheral muscle tissues.…”

Section: E898mentioning

confidence: 90%

Restoring HSP70 deficiencies improves glucose tolerance in diabetic monkeys

Kavanagh

Flynn

Jenkins

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

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We evaluated heat shock protein 70 (HSP70) changes in diabetes mellitus (DM) in a nonhuman primate model. To this end, two studies were conducted in DM vervet monkeys. 1) Normal control and streptozotocin-induced DM monkeys (Stz-DM) that were differentiated into moderately or poorly controlled DM by judicious insulin administration were evaluated. Liver was collected at 4,8,12,16, and 20 wk after streptozotocin, exposed to ex vivo heat shock at 42°C, and immunoblotted for heat shock factor 1 (HSF1), HSP70, and phosphorylated HSF1. 2) Spontaneous DM monkeys that were not pharmacologically induced were included in a crossover study of the HSP70-inducing drug geranylgeranylacetone (GGA). GGA at 20 mg/kg was given for 14 days with a 6-wk washout period. Glucose tolerance testing and plasma and muscle HSP70 were the primary outcome measurements. In Stz-DM, hyperglycemia reduced hepatic HSP70 in a dose-dependent fashion. HSF1 was increased in livers of monkeys with Stz-DM, but responses to ex vivo heat shock were impaired vs. normal monkeys. Activation of HSF1 appears to be important, because the phosphorylation change with heat stress was nearly perfectly correlated with HSP70 increases. Impaired HSF1 activation was also seen in Stz-DM after chronic hyperglycemia (Ͼ12 wk). In naturally occurring DM, increased circulating HSP70 resulted in significantly improved glucose tolerance and significant, positive trends in other measurements of insulin resistance. No change in muscle HSP70 content was observed. We conclude that increasing HSP70, potentially through targeting hyperglycemia-related deficits in HSF1 induction and activation in the liver, is a potent and viable strategy to improve glucose tolerance.heat shock protein 70; chaperone proteins; geranylgeranylacetone; nonhuman primates; diabetes mellitus HEAT SHOCK PROTEINS (HSPs) are the largest family of transcriptionally regulated chaperone proteins that respond to cellular stress. HSPs aid in repair of protein damage and survival of normal cellular functions. Heat shock factor 1 (HSF1) mediates most transcriptional activation by binding to heat shock elements in the promoter region of the HSP genes, with resultant transcription of HSP70 mRNA being most abundant. HSF1 undergoes modifications such as trimerization, phosphorylation, and acetylation as well as product feedback inhibition to modulate the activation-attenuation cycle (1). Induction of HSPs not only protects de novo proteins being translated through the endoplasmic reticulum but also protects oxidized proteins and upregulates intracellular antioxidant mechanisms, which together minimize the chronic inflammatory state associated with insulin resistance (21, 37).Insulin-resistant and hyperglycemic people have reduced HSP70 protein and gene expression (7,9,29). Notably, new studies utilizing chemical chaperones show that insulin sensitivity may be restored in obese rodent models by limiting cellular stress in some tissues (39), and insulin signaling can be improved in obese people (24). Even more compelling...

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“…In addition to the protective role of HSPs, they are also involved in different physiological processes affecting muscle size and function. HSP 70 is involved in FOXO signaling, and HSP 27 is a negative regulator of NF-B in skeletal muscle, and overexpression of these HSPs reduces muscle atrophy during different muscle wasting conditions (160,627). Thus results from the porcine model indicate there is a loss in muscle function when HSP expression is compromised and that a muscle specific difference in HSP expression is one factor underlying the sparing of craniofacial muscles in critically ill ICU patients.…”

Section: Porcine Icu Modelmentioning

confidence: 98%

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

Friedrich

Reid

Berghe

et al. 2015

Physiological Reviews

291

329

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Critical illness polyneuropathies (CIP) and myopathies (CIM) are common complications of critical illness. Several weakness syndromes are summarized under the term intensive care unit-acquired weakness (ICUAW). We propose a classification of different ICUAW forms (CIM, CIP, sepsis-induced, steroid-denervation myopathy) and pathophysiological mechanisms from clinical and animal model data. Triggers include sepsis, mechanical ventilation, muscle unloading, steroid treatment, or denervation. Some ICUAW forms require stringent diagnostic features; CIM is marked by membrane hypoexcitability, severe atrophy, preferential myosin loss, ultrastructural alterations, and inadequate autophagy activation while myopathies in pure sepsis do not reproduce marked myosin loss. Reduced membrane excitability results from depolarization and ion channel dysfunction. Mitochondrial dysfunction contributes to energy-dependent processes. Ubiquitin proteasome and calpain activation trigger muscle proteolysis and atrophy while protein synthesis is impaired. Myosin loss is more pronounced than actin loss in CIM. Protein quality control is altered by inadequate autophagy. Ca 2ϩ dysregulation is present through altered Ca 2ϩ homeostasis. We highlight clinical hallmarks, trigger factors, and potential mechanisms from human studies and animal models that allow separation of risk factors that may trigger distinct mechanisms contributing to weakness. During critical illness, altered inflammatory (cytokines) and metabolic pathways deteriorate muscle function. ICUAW prevention/treatment is limited, e.g., tight glycemic control, delaying nutrition, and early mobilization. Future challenges include identification of primary/secondary events during the time course of critical illness, the interplay between membrane excitability, bioenergetic failure and differential proteolysis, and finding new therapeutic targets by help of tailored animal models.

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Hsp70 prevents disuse muscle atrophy in senescent rats

Cited by 29 publications

References 30 publications

Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Muscle-specific MicroRNA1 (miR1) Targets Heat Shock Protein 70 (HSP70) during Dexamethasone-mediated Atrophy*

Restoring HSP70 deficiencies improves glucose tolerance in diabetic monkeys

The Sick and the Weak: Neuropathies/Myopathies in the Critically Ill

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