Regulation of myocardial heat shock protein 70 gene expression following exercise

Melling, C.W. James; Thorp, David B.; Noble, Earl G.

doi:10.1016/j.yjmcc.2004.05.021

Cited by 36 publications

(42 citation statements)

References 43 publications

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“…The relatively short half-life of Hsp70 mRNA (Theodorakis Table 2 Relative (trained versus control ratio) gene expression and protein amount in rat heart expressed as trained versus control ratio Gene expression was normalized to the housekeeping gene RPL13a, protein amount, evaluated by Western blot, to a-actinin. Repeated independent evaluations were averaged; statistical signiWcance calculation by two-tailed Student t test gave the P values reported between parenthesis ND Not done, NS not signiWcant (P > 0.05) Lennon et al 2004;Moran et al 2004), the underlying mechanism is not well understood (Melling et al 2004). The well known relevance of heat shock proteins in the prevention of cardiovascular diseases (Ji 2002) may involve inhibition of apoptosis (Siu et al 2004) and regulation of Ca2+ homeostasis (Liu et al 2006), but it is likely that the protection conferred by Hsp70 may not be suYcient to explain increased ischemia tolerance (Ronchi et al 2004) and may require additional activities, as for example those provided by HO-1 and Cox-2.…”

Section: Discussionmentioning

confidence: 99%

Mild exercise training, cardioprotection and stress genes profile

et al. 2007

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To improve current knowledge of the molecular mechanisms underlying exercise-induced cardioprotection in a rat model of mild exercise training, Sprague-Dawley rats were trained to run on a treadmill up to 55% of their maximal oxygen uptake for 1 h/day, 3 days/week, 14 weeks, with age-matched sedentary controls (n = 20/group). Rats were sacriWced 48 h after the last training session. Despite lack of cardiac hypertrophy, training decreased blood hemoglobin (7.94 § 0.21 mM vs. 8.78 § 0.23 mM, mean § SE, P = 0.01) and increased both plasma malondialdehyde (0.139 § 0.005 mM vs. 0.085 § 0.009 mM, P = 0.05) and the activity of Mn-superoxide dismutase (11.6 § 0.6 vs. 16.5 § 1.6 mU/ g, P = 0.01), whereas total superoxide dismutase activity was unaVected. When subjected to 30-min ischemia followed by 90-min reperfusion, hearts from trained rats (n = 5) displayed reduced infarct size as compared to controls (37.26 § 0.92% vs. 49.09 § 2.11% of risk area, P = 0.04). The biochemical analyses in the myocardium, which included gene expression proWles, realtime PCR, Western blot and determination of enzymatic activity, showed training-induced upregulation of the following mRNAs and/or proteins: growtharrest and DNA-damage induced 153 (GADD153/ CHOP), heme-oxygenase-1 (HO-1), cyclooxygenase-2 (Cox-2), heat-shock protein 70/72 (HSP70/72), whereas heat-shock protein 60 (HSP60) and glucoseregulated protein 75 (GRP75) were decreased. As a whole, these data indicate that mild exercise training activates a second window of myocardial protection against ischemia/reperfusion by upregulating a number of protective genes, thereby warranting further investigation in man.

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Section: Discussionmentioning

confidence: 99%

Mild exercise training, cardioprotection and stress genes profile

et al. 2007

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“…This dosage of H-89 has been shown to be capable of reducing the myocardial PKA activity by ϳ55% in vivo. 25 All experiments were performed in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of the University of Alabama at Birmingham. The present study used measurement at a single time point, ie, at 2 hours after treatment, and thus it remains unclear whether the salutary effects of E2 in attenuating hepatic injury are sustained for longer periods of time, ie, 24 hours after treatment.…”

Section: Rat Trauma-hemorrhagic Shock Modelmentioning

confidence: 99%

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

Hsieh

Frink

et al. 2007

The American Journal of Pathology

102

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Although nongenomic effects of 17␤-estradiol (E2) are mediated via the estrogen receptor ␣ (ER-␣) , the existence of another novel ER , G protein-coupled receptor 30 (GPR30) , has been suggested as a candidate for triggering a broad range of E2-mediated signaling. GPR30 also acts independently of the ER to promote activation of the protein kinase A (PKA) pathway , which protects cells from apoptosis through Bcl-2. In this study , we examined whether the salutary effects of E2 in attenuating hepatic injury after trauma-hemorrhage are mediated via GPR30-or ER-␣-regulated activation of PKA-dependent signaling. At 2 hours after trauma-hemorrhage , administration of E2-conjugated to bovine serum albumin (E2-BSA , membrane impermeable) or E2 induced the up-regulation of ER-␣ and GPR30 and attenuated hepatic injury. This was accompanied by increases in PKA activity and Bcl-2 expression. Inhibition of PKA in E2-BSA-treated traumahemorrhage rats by PKA inhibitor H89 prevented the E2-BSA attenuation of hepatic injury. Isolated hepatocytes were transfected with small interfering RNA to suppress GPR30 or ER. We found that suppression of GPR30 but not ER-␣ prevented E2-BSAor E2-induced PKA activation and Bcl-2 expression. These results suggest that the nongenomic salutary effect of E2 in reducing hepatic injury after traumahemorrhage is mediated through the PKA-dependent pathway via GPR30 but not ER-␣. (Am J Pathol

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“…PKC has been implicated in the posttranslational phosphorylation and regulation of several key cardioprotective cytosolic proteins (Ping et al 1999) and one potential target is the inducible member of the 70-kDa heat-shock family, Hsp70, which has been demonstrated to be at least partially responsible for exercise-induced myocardial protection during I/R-injury (Paroo et al 2002). It has been reported that activation of PKC is not responsible for the exercise-induced, transcriptional expression of Hsp70 (Melling et al 2004); however, it may play a role in the posttranslational modification of cardiac Hsp70 and its subsequent function (Joyeux et al 1997). In other tissues, including the liver (Gonzalez and Manso 2004), and extensor digitorum longus and soleus muscles (Hernando and Manso 1997), it has been shown that Hsp70 undergoes posttranslational modification through phosphorylation following exercise.…”

Section: Introductionmentioning

confidence: 99%

Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise

Melling

Thorp

Milne

et al. 2009

Cell Stress and Chaperones

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Both protein kinase C (PKC) activation and Hsp70 expression have been shown to be key components for exercise-mediated myocardial protection during ischemia-reperfusion injury. Given that Hsp70 has been shown to undergo inducible phosphorylation in striated muscle and liver, we hypothesized that PKC may regulate myocardial Hsp70 function and subsequent exercise-conferred cardioprotection through this phosphorylation. Hence, acute exercise of male Sprague-Dawley rats (30 m/min for 60 min at 2% grade) was employed to assess the role of PKC and its selected isoforms in phosphorylation of Hsp70 and protection of the myocardium during ischemia-reperfusion injury. It was observed that administration of the PKC inhibitor chelerythrine chloride (5 mg/kg) suppressed the activation of three exercise-induced PKC isoforms (PKCα, PKCδ, and PKCɛ) and attenuated the exercisemediated reduction of myocardial infarct size during ischemia-reperfusion injury. While this study also demonstrated that exercise led to an alteration in the phosphorylation status of Hsp70, this posttranslational modification appeared to be dissociated from PKC activation, as exercise-induced phosphorylation of Hsp70 was unchanged following inhibition of PKC. Taken together, these results indicate that selected isoforms of PKC play an important role in exercise-mediated protection of the myocardium during ischemia-reperfusion injury. However, exerciseinduced phosphorylation of Hsp70 does not appear to be a mechanism by which PKC induces this cardioprotective effect.

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Regulation of myocardial heat shock protein 70 gene expression following exercise

Cited by 36 publications

References 43 publications

Mild exercise training, cardioprotection and stress genes profile

Mild exercise training, cardioprotection and stress genes profile

G Protein-Coupled Receptor 30-Dependent Protein Kinase A Pathway Is Critical in Nongenomic Effects of Estrogen in Attenuating Liver Injury after Trauma-Hemorrhage

Myocardial Hsp70 phosphorylation and PKC-mediated cardioprotection following exercise

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