PERK MEDIATED ENDOPLASMIC RETICULUM STRESS IS INVOLVED IN ANGIOTENSINIIINDUCED CARDIAC HYPERTROPHY

Objectives To investigate the role of protein kinase R-like ER kinase (PERK)-mediated endoplasmic reticulum stress (ERS) in angiotensin II, and to explore the role of taurine (Tau), the ERS inhibitor, in Ang II-induced cardiomyocyte hypertrophy. Methods In the model of Ang II-induced cardiomyocyte hypertrophy from neonatal Sprague-Dawley rats, morphological studies, 3H-Leucine incorporation and surface area were employed to assess cardiac hypertroph. Real time PCR, RT-PCR and Western blotting were used to detected mRNA and protein expression of glucose-regulated protein 78 (GRP78), calreticulin (CRT), PERK, eukaryotic initiation factor 2α(eIF2α), (C/EBP) homologous protein (CHOP). Cultured cardiomyocytes were treated with Tau prior to Ang II treatment, and then detected the status of cardiomyocytes and ER stress-related molecular. Results Compared with control group, angiotensin II treated cardiomyocytes showed that CRT mRNA and protein expression increased by 146.4% and 125.3%, respectively (p<0.05); GRP78 mRNA and protein expression increased by 84% and 77.6%, respectively (p<0.05). And PERK mRNA and protein expression increased by 165.4% and 132.1%, respectively (p<0.05); eIF2α mRNA and protein expression were increased by 110.9% and 46.5%, respectively (p<0.05); CHOP mRNA and protein expression increased by 117.7% and 63.3%, respectively (p<0.05). Compared with Ang II group, Ang II+Tau group showed that ANP and BNP mRNA expression decreased by 57.5% and 38.4%, respectively (p<0.05), protein synthesis rate decreased by 32.5% (p<0.05), surface area decrease by 33% (p<0.05). And taurine decreased mRNA and protein expression levels of CRT in Ang II-induced cardiomyocytes by 57.6% and 43.1% (p<0.05), those of GRP78 by 60.6% and 33.3% (p<0.05), those of PERK by 31.7% and 43.5% (p<0.05), those of eIF2α by 56.2% and 17.8% (p<0.05), those of CHOP by 62.7% and 37.4% (p<0.05). Conclusions Ang II treatment up-regulated the mRNA and protein level of CRT, GRP78, PERK, eIF2α and CHOP in cardiomyocytes, indicating that Ang II could induce ER stress response in cultrued cardiomyocytes. Tau down-regulated expression of ANP and BNP, protein synthesis rate, and cell surface area induced by Ang II. Tau also down-regulated expression of ER stress-related molecules. Our data indicated that PERK-mediated ERS is involved in Ang II-induced cardiomyocyte hypertrophy, and Tau attenuated Ang II-induced cardiomyocyte hypertrophy through suppressing ERS