MAPKs抑制剂对大鼠肝细胞GSH代谢相关酶的影响

doi:10.12047/j.cjap.5601.2017.118

中国应用生理学杂志 ›› 2017, Vol. 33 ›› Issue (6): 497-500.doi: 10.12047/j.cjap.5601.2017.118

MAPKs抑制剂对大鼠肝细胞GSH代谢相关酶的影响

高蔚娜, 蒲玲玲, 韦京豫, 辛中豪, 王亚雯, 石塔拉, 李天, 郭长江

军事医学科学院卫生学环境医学研究所, 天津 300050

收稿日期:2016-08-19 修回日期:2017-05-21 出版日期:2017-11-28 发布日期:2018-06-19
基金资助:
国家自然科学基金面上项目（81372988）；天津市应用基础与前沿技术研究计划（青年基金项目，13JCQNJC11800）

Effects of MAPKs inhibitors on GSH metabolic enzymes in rat hepatocytes

GAO Wei-na, PU Ling-ling, WEI Jing-yu, XIN Zhong-hao, WANG Ya-wen, SHI Ta-la, LI Tian, GUO Chang-jiang

Department of Nutrition, Institute of Health and Environmental Medicine, Academy of Military Medical Sciences, Tianjin 300050, China

Received:2016-08-19 Revised:2017-05-21 Online:2017-11-28 Published:2018-06-19
Contact: 蒲玲玲,Tel:022-84655429;E-mail:pulingling@163.com;郭长江,E-mail:guocjtj@126.com E-mail:pulingling@163.com;guocjtj@126.com
Supported by:
国家自然科学基金面上项目（81372988）；天津市应用基础与前沿技术研究计划（青年基金项目，13JCQNJC11800）

摘要/Abstract

摘要： 目的：观察丝裂原活化的蛋白激酶（MAPKs）抑制剂对大鼠肝细胞谷胱甘肽（GSH）代谢的影响，确定哪条途径与GSH代谢相关。方法：体外培养BRL大鼠肝细胞，以c-Jun NH2-末端激酶（JNK）途径抑制剂SP600125、p38途径抑制剂SB203580、细胞外信号调节激酶1/2（ERK1/2）途径抑制剂PD98659处理24 h，采用MTT法测定细胞活力，高效液相色谱法测定细胞内GSH含量，Luminex法测定JNK和磷酸化JNK （p-JNK）的蛋白表达，采用试剂盒测定GSH代谢酶活性。结果：SP600125浓度>5 μmol/L，SB203580浓度>20 μmol/L，PD98659浓度>40 μmol/L时，细胞活力受抑制；SP600125能显著减少大鼠肝细胞内还原型GSH的含量，SB203580和PD98659作用不明显；SP600125显著减少磷酸化JNK （p-JNK）蛋白表达，显著增强谷胱甘肽过氧化物酶（GSH-Px）的活力。结论：JNK MAPK途径参与了大鼠肝细胞GSH的代谢。

关键词: MAPKs抑制剂, 谷胱甘肽, 代谢, BRL细胞株

Abstract: Objective: To investigate the effects of mitogen-activated protein kinases (MAPKs) inhibitors on glutathione (GSH) metabolism, and to explore the pathway related to GSH metabolism.Methods: BRL rat hepatocytes were treated by c-Jun NH2-terminal kinase (JNK),p38, and extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitors:SP600125, SB203580 and PD98659, respectively, for 24 h. MTT method was used to measure hepatocytes viability. The content of GSH was determined by high performance liquid chromatography. The protein expressions of JNK and phosphorylated JNK (p-JNK) was tested by Luminex method. Activities of GSH metabolic enzymes were detected by commercial kits.Results: Hepatocytes vitality was inhibited when the concentrations of SP600125, SB203580 and PD98659 were higher than 10 μmol/L, 20 μmol/L, and 40 μmol/L, respectively; SP600125 decreased the content of GSH in hepatocytes, while SB203580 and PD98659 had no effect. SP600125 reduced p-JNK protein expression, and enhanced GSH-Px activity significantly.Conclusion: JNK MAPK pathway takes part in the GSH metabolism in hepatocytes.

Key words: MAPKs inhibitor, glutathione, metabolism, BRL cell line

高蔚娜, 蒲玲玲, 韦京豫, 辛中豪, 王亚雯, 石塔拉, 李天, 郭长江. MAPKs抑制剂对大鼠肝细胞GSH代谢相关酶的影响[J]. 中国应用生理学杂志, 2017, 33(6): 497-500.

GAO Wei-na, PU Ling-ling, WEI Jing-yu, XIN Zhong-hao, WANG Ya-wen, SHI Ta-la, LI Tian, GUO Chang-jiang. Effects of MAPKs inhibitors on GSH metabolic enzymes in rat hepatocytes[J]. CJAP, 2017, 33(6): 497-500.

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MAPKs抑制剂对大鼠肝细胞GSH代谢相关酶的影响

Effects of MAPKs inhibitors on GSH metabolic enzymes in rat hepatocytes

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