Changes in the rat heart proteome induced by exercise training: Increased abundance of heat shock protein hsp20

Abstract

Chronic exercise training elicits adaptations in the heart that improve pump function and confer cardioprotection. To identify molecular mechanisms by which exercise training stimulates this favorable phenotype, a proteomic approach was employed to detect rat cardiac proteins that were differentially expressed or modified after exercise training. Exercise-trained rats underwent six weeks of progressive treadmill training five days/week, 0% grade, using an interval training protocol. Sedentary control rats were age- and weight-matched to the exercise-trained rats. Hearts were harvested at various times (0-72 h) after the last bout of exercise and were used to generate 2-D electrophoretic proteome maps and immunoblots. Compared with hearts of sedentary rats, 26 protein spot intensities were significantly altered in hypertrophied hearts of exercise-trained rats (p <0.05), and 12 spots appeared exclusively on gels from hearts of exercise-trained rats. Immunoblotting confirmed that chronic exercise training, but not a single bout of exercise, elicited a 2.5-fold increase in the abundance of one of the candidate proteins in the heart, a 20 kDa heat shock protein (hsp20) that persisted for at least 72 h of detraining. Thus, exercise training alters the cardiac proteome of the rat heart; the changes include a marked increase in the expression of hsp20.

Human Mutation in the Anti-apoptotic Heat Shock Protein 20 Abrogates Its Cardioprotective Effects

“…At basal levels, no phosphorylated Hsp20 could be detected, consistent with the low activity of PKA in isolated myocytes. To test the specificity of this antibody, peptide competition was performed with the anti- [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] in human, dog, rat, and mouse shows that proline 20 is fully conserved. B, secondary structure predictions revealed alterations in the helical content around the Ser 16 phosphorylation site as well as around the site of the mutation.…”

“…In recent years, Hsp20 and its phosphorylation have emerged to be functionally significant in the heart. Interestingly, the levels of Hsp20 have been shown to increase under the physiological stress of exercise training (11), as well as in the pathological setting of chronic ␤-adrenergic stimulation (7) and in tachycardia-induced heart failure (12). Using adenovirus-infected cardiomyocytes and transgenesis, we and others have demonstrated that this increase is cardioprotective (7,(13)(14)(15)(16)(17).…”

Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

“…Consistently, a subsequent study by Fan indicated that HSPB6 overexpression in the heart was associated with better recovery of cardiac function and reduced infarction in the following I/R injury [76]. Conversely, transgenic mice with cardiac-specific overexpression of miR-320 revealed an increased extent of apoptosis and infarction size in the hearts on I/R relative to the wild-type controls via antithetical regulation of HSPB6 [26]. Mechanistic studies unveiled that HSPB6 directly interacted with Bax and the cardioprotective effect may be mediated through preventing Bax translocation to the mitochondria, which blocked the initiation of apoptosis [76].…”

“…Although expression of HSPB6 did not seem to be heat-inducible in rat tissue [1], heat pretreatment of swine carotid artery was associated with increased HSPB6 and ser16-HSPB6 phosphorylation level [24]. Transiently increased HSPB6 levels in rat heart were observed upon LPS stimulation [25], after exercise training [26] and under doxorubicin treatment [27]. HSPB6 levels and phosphorylation were strongly upregulated upon β-agonist stimulation [8], as well as in tachycardia-induced canine failing heart [28].…”

Proteomics in the study of organ dysfunction

“…It is possible that one protein within multiple cell types is committed to only one organ function or many, while many proteins within one cell type may operate one function, as illustrated in FIGURE 1. It is encouraging that there is a growing number of proteomic scientists who are begining to explore the utilization of proteomics in the evaluation of cell or organ function. For example, a proteomic approach was employed to detect rat cardiac proteins that were differentially expressed or modified after exercise training [8]. A total of 26 protein spot intensities were found to be significantly altered in hypertrophied hearts, with a marked increase in the expression of heat-shock protein 20.…”