[Study on antagonistic effect of liangxue huayu recipe on endoplasmic reticulum stress-induced L02 hepatocyte apoptosis and its mechanism].
Endoplasmic reticulum stress (ERS) is a new pathway inducing cell apoptosis that has been discovered in recent years. This study focused on the protective effect of Liangxue Huayu recipe (LHR) on tumor necrosis factor-alpha (TNF-alpha) and D-GalN-induced hepatocyte apoptosis. It found that TNF-alpha and D-GalN could obviously inhibit hepatocyte proliferation, induce cell apoptosis, and significantly increase free calcium ions in cytoplasms, as well as protein expressions of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. After the administration of LHR of different concentrations, compared with the TNF-alpha/GalN injury group, LHR could significantly alleviated L02 hepatocyte proliferation, decreased cell apoptosis, inhibited growth of intracytoplasmic free calcium content, and gradually reduced the protein expressions of phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP. These findings indicated that LHR has the inhibitory effect on TNF-alpha and D-GalN-induced hepatocyte apoptosis. Its mechanism may be related to down-regulation of ERS apoptosis-related signal molecules phosphorylated PERK, phosphorylated elF2alpha, cleaved Caspase-12, GRP78 and CHOP that maintain calcium homeostasis in endoplasmic reticulum.
Nanjing University of Chinese Medicine, Nanjing 210023, China. jiangjzq@sina.com
Ze-Qun
ZQ
Jiang
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Zhi-Hua
ZH
Yao
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Zheng-Ting
ZT
Deng
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Xin-Chao
XC
Jiang
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Xiao-Jing
XJ
Yan
Nanjing University of Chinese Medicine, Nanjing 210023, China.
Wei-Ping
WP
Chen
D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D004365:Drugs, Chinese Herbal; D000091342:Endoplasmic Reticulum Chaperone BiP; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D014409:Tumor Necrosis Factor-alpha; C496319:NOS2 protein, human; D052247:Nitric Oxide Synthase Type II