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

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.

The mTOR/p70S6K signal transduction pathway plays a role in cardiac hypertrophy and influences expression of myosin heavy chain genes in vivo.

OBJECTIVE: Rapamycin inhibits p70 S6 kinase (p70(S6K)) activity and hypertrophy of cultured neonatal rat cardiac myocytes. The purpose of the present study was to determine whether rapamycin inhibits left ventricular (LV) hypertrophy in intact rats and whether it alters cardiac gene expression. METHODS: 300 g rats were subjected to aortic constriction (AC) or sham-operation (SH) and studied 2 and 3 days after surgery. Beginning 1 day prior to surgery, rats were injected with rapamycin (1.5 mg/kg, i.p.) or carboxymethylcellulose vehicle (V), yielding 4 groups (SH-V, SH-R, AC-V, AC-R). Total RNA was extracted for determination of mRNA levels by Northern blotting. RESULTS: LV dry weight/body weight ratios were 0.43 +/- 0.04 (mean +/- SE) for SH-V, 0.46 +/- 0.02 for SH-R, 0.56 +/- 0.02 for AC-V, and 0.53 +/- 0.03 for AC-R. R inhibited cardiac hypertrophy induced by pressure overload (ANOVA; p < 0.05). Rapamycin had no effect on the expression of atrial natriuretic factor mRNA, but increased the levels of beta-myosin heavy chain mRNA 6-fold in hearts of SH-R and AC-R compared to SH-V. Rapamycin also increased the expression of alpha-myosin heavy chain mRNA in SH-R by 3-fold compared with SH-V, but had no effect on the AC-R group. CONCLUSION: The data suggest that an intact mTOR signaling pathway is required for rapid hypertrophic growth of the heart in vivo. Moreover, the data suggest a novel link between the mTOR/p70(S6K) signal transduction pathway and pretranslational control of myosin gene expression in the heart.