摘要
目的:研究蛋白激酶R样内质网激酶(PERK)介导的内质网应激(ERS)反应在血管紧张素Ⅱ(AngⅡ)诱导心肌细胞肥大中的作用。方法:在AngⅡ诱导原代培养的乳大鼠心肌细胞肥大模型上,采用[3H]-亮氨酸掺入、心肌细胞表面积测定等评估心肌细胞肥大程度;以实时定量PCR、RT-PCR和Western blotting检测ERS标志性分子葡萄糖调节蛋白78(GRP78)、钙网蛋白(CRT)、蛋白激酶R样内质网激酶(PERK)、真核细胞翻译起始因子2α(eIF2α)和C/EBP同源蛋白(CHOP)mRNA和蛋白表达变化。结果:与正常对照组比较,AngⅡ组CRTmRNA和蛋白表达分别高146.4%和125.3%(P<0.05),GRP78 mRNA和蛋白的表达分别高84.0%和77.6%(P<0.05),PERK mRNA和蛋白表达分别高165.4%和132.1%(P<0.05),eIF2αmRNA和蛋白表达分别高110.9%和46.5%(P<0.05),CHOP mRNA和蛋白表达分别高117.7%和63.3%(P<0.05)。结论:PERK介导的内质网应激反应参与了AngⅡ诱导的心肌细胞肥大。
AIM ： To investigate the role of protein kinase R - like endoplasmic reticulum kinase （PERK） - mediated endoplasmic reticulum stress （ERS） in angiotensin Ⅱ （ Ang Ⅱ） - induced myocardial hypertrophy. METH- ODS： In the hypertrophy model of Ang Ⅱ- induced cardiomyocytes isolated from neonatal Sprague - Dawley rats, the methods of morphological observation, [ 3 H] - leucine incorporation and surface area measurement were employed to assess the cardiomyocyte hypertrophy. Real -time PCR, RT -PCR and Western blotting were used to detected the expression of glucose - regulated protein 78 （ GRP78 ）, calreticulin （ CRT）, PERK, eukaryotic initiation factor 2ct （eIF2oL） and C/EBP homologous protein （CHOP） at mRNA and protein levels. RESULTS： Compared with control group, Ang II -treated car- diomyocytes showed that the mRNA and protein expression of CRT increased by 146. 4% and 125.3%, respectively （P 〈 0. 05）. The mRNA and protein expression of GRP78 increased by 84. 0% and 77. 6%, respectively （P 〈0. 05）. The mR- NA and protein expression of PERK increased by 165.4% and 132. 1% , respectively （ P 〈 0. 05 ）. The mRNA and protein expression of eIF2a was increased by 110. 9% and 46. 5% , respectively （P 〈0. 05）. The mRNA and protein expression of CHOP also increased by 117.7% and 63.3%, respectively （P 〈0. 05）. CONCLUSION： PERK - mediated ERS re- sponse is involved in AngⅡ-induced cardiomyocyte hypertrophy.
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2012年第7期1153-1159,共7页
Chinese Journal of Pathophysiology
基金
国家自然科学基金资助项目(No.81070130)
关键词
心肌肥大
内质网应激
蛋白激酶R样内质网激酶
Cardiac hypertrophy
Endoplasmic reticulum stress
Protein kinase R - like endoplasmic reticu- lum kinase
