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番茄红素减轻H9C2心肌细胞缺氧/复氧致内质网应激的相关机制(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2017年第2期
页码:
138-143
栏目:
基础研究
出版日期:
2016-11-25

文章信息/Info

Title:
Mechanism of lycopene in alleviating endoplasmic reticulum stress induced by hypoxia/reoxygenation in H9C2 cardiomyocytes
作者:
高 扬1; 邢长泰2; 贾大林1
（1.中国医科大学附属一院心内科，辽宁 沈阳 110001；
2.沈阳医学院附属中心医院，辽宁 沈阳 110000）
Author(s):
GAO Yang1;  XING Chang-tai2;  JIA Da-lin1
(1.Department of Cardiovascology, First Affiliated Hospital, China Medical University, Shenyang 110001, Liaoning, China；
2.Central Hospital, Shenyang Medical College, Shenyang 110000, Liaoning, China)
关键词:
番茄红素; 缺氧/复氧; 内质网应激; Caspase-12; CHOP; p-JNK
Keywords:
lycopene;  hypoxia/reoxgenation;  endoplasmic reticulum stress;  CHOP;  caspase-12;  p-JNK
分类号:
R978.5
DOI:
-
文献标识码:
A
摘要:
目的 探讨番茄红素减轻H9C2心肌细胞缺氧/复氧(H/R)致内质网应激(ERS)的相关机制。方法 H9C2心肌细胞随机分为:①空白对照组、②番茄红素组、③H/R组、④番茄红素+H/R组、⑤4-苯基丁酸（4-phenyl butyric acid，4-PBA）+H/R组、⑥毒胡萝卜素内酯（thapsigargin，TG）组、⑦番茄红素+TG组。流式细胞术检测H9C2心肌细胞凋亡比例；Western blot检测葡萄糖调节蛋白(glucose-regulated proteins,GRP)78、C/EBP环磷酸腺苷反应元件结合转录因子同源蛋白(C/EBP homologous protein,CHOP)、c-Jun氨基末端激酶(c-Jun-N-terminal protein kinase,JNK)、磷酸化JNK（p-JNK）及半胱氨酸天冬氨酸蛋白酶(Casepase)-12的表达。结果 与对照组相比，H/R组及TG组细胞的细胞凋亡比例、GRP78、CHOP、p-JNK和Caspase-12蛋白表达量明显增加（P<0.01）；与H/R组相比，细胞凋亡比例及上述蛋白表达在番茄红素+H/R组与4-PBA+H/R组明显下降（P<0.01）；与TG组相比，细胞凋亡比例及上述蛋白表达在番茄红素+TG组也明显下降（P<0.01）；而番茄红素+H/R组与4-PBA+H/R组相比差异不具有统计学意义。JNK蛋白总量表达无明显变化。结论 番茄红素通过抑制ERS致凋亡的相关信号通路CHOP、p-JNK和Caspase-12对H/R H9C2心肌细胞起到保护作用。
Abstract:
AIM To explore the possible mechanism of lycopene in alleviating endoplasmic reticulum stress (ERS) induced by hypoxia/reoxygenation (H/R) in H9C2 cardiomyocytes. METHODS H9C2 cardiomyocytes were randomly divided into control group, lycopene group, H/R group, lycopene+H/R group, 4-phenyl butyric acid (4-PBA)+H/R group, thapsigargin (TG) group, and lycopene+TG group. The apoptosis ratio of H9C2 cardiomyocytes was detected and the expressions of protein of glucose-regulated proteins 78 (GRP78), C/EBP homologous protein (CHOP), c-Jun-N-terminal protein kinase (JNK), phosphorylation of JNK (p-JNK) and caspase-12 were detected by Western blot. RESULTS The apoptosis ratio and the expressions of protein of GRP78, CHOP, JNK, p-JNK and caspase-12 increased markedly in H/R group and TG group in comparison with those in the control group (P<0.01). They decreased markedly in lycopene+H/R group and 4-PBA+H/R group compared with those in H/R group (P<0.01) and in lycopene+TG group compared with those in TG group (P<0.01). No statistically significant difference was found between lycopene+H/R group and 4-PBA+H/R group. No significant difference was found in the changes of the expression of protein of JNK. CONCLUSION Lycopene may exert its protective effect on H/R H9C2 cardiomyocytes through inhibiting the key signaling pathways of CHOP, p-JNK and caspase-12 to reduce ERS.

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备注/Memo

备注/Memo:
收稿日期：2015-12-11.
通讯作者：贾大林，教授，主要从事冠心病基础研究 Email:JDL2001@263.net
作者简介：高扬，博士生 Email:weihai19822008@163.com
更新日期/Last Update: 2016-10-11