ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression
文献类型：期刊论文
| 作者 | Wang, Chunxia; Li, Houkai; Meng, Qingshu; Du, Ying; Xiao, Fei; Zhang, Qian; Yu, Junjie; Li, Kai; Chen, Shanghai（陈上海）; Huang, Zhiying |
| 刊名 | JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
 |
| 出版日期 | 2014 |
| 卷号 | 18期号:1页码:80-90 |
| 关键词 | ATF4 primary hepatocytes CYP2E1 oxidative stress ROS TG accumulation |
| 通讯作者 | Guo, FF (reprint author), Chinese Acad Sci, Grad Sch, Key Lab Nutr & Metab, Inst Nutr Sci,Shanghai Inst Biol Sci, 294 Taiyuan Rd, Shanghai 200031, Peoples R China. |
| 英文摘要 | Activating transcription factor (ATF) 4 is involved in the regulation of oxidative stress in fibroblasts and neurons. The role of ATF4 in hepatocytes, however, is unknown. The aim of this study was to investigate the role of ATF4 in hepatocytes in oxidative stress under a high-fat diet (HFD). Here, we showed that palmitate-stimulated reactive oxygen species (ROS) production and triglyceride (TG) accumulation is blocked by ATF4 deficiency in primary hepatocytes. Consistently, HFD-induced oxidative stress, TG accumulation and expression of cytochrome P450, family 2, subfamily, polypeptide 1 (CYP2E1) are also blocked by knocking down ATF4 expression in the mouse liver. This suggests that ATF4 might regulate oxidative stress via CYP2E1 under an HFD. In addition, we observed that expression of CYP2E1 is indirectly regulated by ATF4 in a cAMP-responsive element binding protein (CREB)-dependent manner, which can directly activate the CYP2E1 promoter activity. Notably, ATF4-stimulated ROS production is inhibited in vivo by treatment with diallyl sulphide, a selective CYP2E1 inhibitor. Finally, we showed that ATF4 expression in the liver is responsible for the protective effects against HFD-induced CYP2E1 expression, oxidative stress, and TG accumulation. Taken together, these observations suggest that ATF4 is a novel regulator of oxidative stress as well as accumulation of TG in response to HFD. |
| 类目[WOS] | Cell Biology ; Medicine, Research & Experimental |
| 研究领域[WOS] | Cell Biology ; Research & Experimental Medicine |
| 关键词[WOS] | NONALCOHOLIC FATTY LIVER ; CAMP-RESPONSE ELEMENTS ; LONG-TERM FACILITATION ; INDUCED OBESE MICE ; GROWTH-FACTOR 21 ; TRANSCRIPTION FACTOR ; INSULIN-RESISTANCE ; HEPATIC STEATOSIS ; IN-VIVO ; STEATOHEPATITIS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000328951400008 |
| 公开日期 | 2016-02-26 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/427]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_代谢的遗传与营养调控研究组 |
| 推荐引用方式 GB/T 7714 | Wang, Chunxia,Li, Houkai,Meng, Qingshu,et al. ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,2014,18(1):80-90. |
| APA | Wang, Chunxia.,Li, Houkai.,Meng, Qingshu.,Du, Ying.,Xiao, Fei.,...&Guo, Feifan.(2014).ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression.JOURNAL OF CELLULAR AND MOLECULAR MEDICINE,18(1),80-90. |
| MLA | Wang, Chunxia,et al."ATF4 deficiency protects hepatocytes from oxidative stress via inhibiting CYP2E1 expression".JOURNAL OF CELLULAR AND MOLECULAR MEDICINE 18.1(2014):80-90. |
入库方式： OAI收割
来源：上海营养与健康研究所
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