4-phenylbutyric acid attenuates endoplasmic reticulum stress-mediated apoptosis and protects the hepatocytes from intermittent hypoxia-induced injury

被引:17
作者
Liu Xin [1 ]
Wu Fan [1 ]
Du Tingting [1 ]
Sun Zuoming [2 ]
Zhang Qiang [1 ]
机构
[1] Tianjin Med Univ, Geriatr, Inst Gerontol Tianjin, Gen Hosp, 154 Anshan Rd, Tianjin, Peoples R China
[2] City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA USA
关键词
Intermittent hypoxia; Liver injury; Endoplasmic reticulum stress; Apoptosis; 4-phenylbutyric acid; OBSTRUCTIVE SLEEP-APNEA; FATTY LIVER-DISEASE; CELL-DEATH; HEPATOTOXICITY; MITOCHONDRIA; MECHANISMS; INDUCTION; PATHWAY; DAMAGE; 4-PBA;
D O I
10.1007/s11325-018-1739-y
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Purpose To investigate the effect of 4-phenylbutyric acid (4-PBA) on intermittent hypoxia (IH)-induced liver cell injury and to clarify the underlying mechanisms. Methods L02 cells (normal human liver cells) were cultured in normoxic condition or subjected to intermittent hypoxia for 4, 8, and 12h. A part of hypoxia-treated L02 cells was applied with 4-PBA 1h before exposure to hypoxia. The effect of 4-PBA on liver injury, hepatocyte apoptosis, endoplasmic reticulum stress (ERS), and PERK-eIFa2-ATF4-CHOP apoptotic pathway was investigated. Results (1) IH caused apoptosis in hepatocyte; (2) IH caused ERS in hepatocyte; (3) IH caused hepatic injury; (4) 4-PBA attenuated IH-induced liver cell injury; (5) 4-PBA protected liver cell from IH-induced apoptosis; (6) 4-PBA suppressed ERS-related apoptotic pathway (PERK-eIFa2-ATF4-CHOP), but did not suppress IH-induced unfold protein reaction (UPR). Conclusions 4-PBA could protect liver cells by suppressing IH-induced apoptosis mediated by ERS, but not by reducing the UPR.
引用
收藏
页码:711 / 717
页数:7
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