气候变化领域集成服务门户(CCPortal): An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis

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DOI	10.1126/science.aay0542
	An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis
	Zhao P.; Sun X.; Chaggan C.; Liao Z.; Wong K.I.; He F.; Singh S.; Loomba R.; Karin M.; Witztum J.L.; Saltiel A.R.
发表日期	2020
ISSN	0036-8075
起始页码	652
结束页码	660
卷号	367 期号:6478
英文摘要	Liver cell death has an essential role in nonalcoholic steatohepatitis (NASH). The activity of the energy sensor adenosine monophosphate (AMP)–activated protein kinase (AMPK) is repressed in NASH. Liver-specific AMPK knockout aggravated liver damage in mouse NASH models. AMPK phosphorylated proapoptotic caspase-6 protein to inhibit its activation, keeping hepatocyte apoptosis in check. Suppression of AMPK activity relieved this inhibition, rendering caspase-6 activated in human and mouse NASH. AMPK activation or caspase-6 inhibition, even after the onset of NASH, improved liver damage and fibrosis. Once phosphorylation was decreased, caspase-6 was activated by caspase-3 or -7. Active caspase-6 cleaved Bid to induce cytochrome c release, generating a feedforward loop that leads to hepatocyte death. Thus, the AMPK–caspase-6 axis regulates liver damage in NASH, implicating AMPK and caspase-6 as therapeutic targets. © 2020 American Association for the Advancement of Science. All rights reserved.
关键词	6,7 dihydro 4 hydroxy 3 (2' hydroxy 1,1' biphenyl 4 yl) 6 oxothieno[2,3 b]pyridine 5 carbonitrile adenosine phosphate caspase 3 caspase 6 caspase 7 cytochrome c hydroxymethylglutaryl coenzyme A reductase kinase matrix metalloproteinase apoptosis cytochrome enzyme enzyme activity inhibition protein rodent AMPK signaling animal experiment animal model animal tissue apoptosis Article C57BL 6 mouse cell death controlled study drug mechanism enzyme activation enzyme activity enzyme inhibition enzyme phosphorylation enzyme repression gene knockout human human cell human tissue liver cell liver fibrosis liver injury male mouse nonalcoholic steatohepatitis nonhuman priority journal protein cleavage protein secretion
语种	英语
来源机构	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/133737
推荐引用方式 GB/T 7714	Zhao P.,Sun X.,Chaggan C.,等. An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis[J]. Science,2020,367(6478).
APA	Zhao P..,Sun X..,Chaggan C..,Liao Z..,Wong K.I..,...&Saltiel A.R..(2020).An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis.,367(6478).
MLA	Zhao P.,et al."An AMPK–caspase-6 axis controls liver damage in nonalcoholic steatohepatitis".367.6478(2020).