| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 101 === Today, the study of decelerating the progression of myocardial infarction (MI) to heart failure is an important issue to reduce cardiovascular mortality. Our first part study showed the metabolism shift during sub-acute phase which is the period 2 day- 6 week after MI. Endoplasmic reticulum stress is often accompanied with metabolism disorder and induces cell death. Estrogen receptor β (ER β) has been showed that elicits cardio-protections. Since endoplasmic reticulum -mitochondrial coupling modulates calcium mobilization, in this study, we investigated whether activation of ER β protects the infaracted hearts by changing the coupling between endoplasmic reticulum and mitochondria by using comparative proteome, conventional western blotting analysis. Long chain fatty acid palmitic acid (PA)-treated H9c2 (cardiomyoblasts) was used as our in vitro model. Echocardiographic analysis showed functional impairments in sub-acute infarcted hearts. Ventricular protein expression of long chain acyl-CoA dehydrogenase and endoplasmic reticulum stress-related survival protein double stranded RNA-dependent protein kinase were decreased and showed positive correlation with fractional shortening, while cell cycle and apoptosis related protein (CARP1) and apoptosis-induced factor (AIF) were not altered. PA induced cell death with increase of ER stress-related apoptotic protein CCAAT-enhancer-binding protein homologous protein not influences of CARP -1and AIF. Daily intraperitoneal administration with DPN (ER β agonist) for 14 days showed improvement on cardiac function with the increase of left ventricular internal diameter in the systolic phase. In addition, ER β prevented PA-induced cell death but did not change apoptotic protein expression. Proteomic data showed the enhanced expression of proteins related with oxidative phosphorylation and calcium mobilization by DPN. Taken together, these results suggest that ER β has potential effect to preserve cardiac function during the sub-acute phase of MI by modulating the endoplasmic reticulum -mitochondrial coupling. Further studies of the endoplasmic reticulum -mitochondrial coupling on sub-acute infracted hearts may provide an alternative pathway to prevent heart failure.
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