Silent information regulator sirtuin 1 ameliorates acute liver failure via the p53/glutathione peroxidase 4/gasdermin D axis
作者机构：Department of Infectious DiseasesThe Affiliated Hospital of Guizhou Medical UniversityGuizhou Medical UniversityGuiyang 550004Guizhou ProvinceChina Department of Infectious DiseasesGuizhou Provincial People's HospitalGuiyang 550001Guizhou ProvinceChina
出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)
年 卷 期：2024年第30卷第11期
页 面：1588-1608页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
基 金：Supported by National Natural Science Foundation of China,No.82060123 Doctoral Start-up Fund of Affiliated Hospital of Guizhou Medical University,No.gysybsky-2021-28 Fund Project of Guizhou Provincial Science and Technology Department,No.1Y299 Guizhou Provincial Health Commission,No.gzwjk2019-1-082
主 题：Silent information regulator sirtuin 1 Ferroptosis Pyroptosis p53/glutathione peroxidase 4/gasdermin D Acute liver failure
摘 要：BACKGROUND Acute liver failure(ALF)has a high mortality with widespread hepatocyte death involving ferroptosis and *** silent information regulator sirtuin 1(SIRT1)-mediated deacetylation affects multiple biological processes,including cellular senescence,apoptosis,sugar and lipid metabolism,oxidative stress,and *** To investigate the association between ferroptosis and pyroptosis and the upstream regulatory *** This study included 30 patients with ALF and 30 healthy individuals who underwent serum alanine aminotransferase(ALT)and aspartate aminotransferase(AST)testing.C57BL/6 mice were also intraperitoneally pretreated with SIRT1,p53,or glutathione peroxidase 4(GPX4)inducers and inhibitors and injected with lipopolysaccharide(LPS)/D-galactosamine(D-GalN)to induce *** D(GSDMD)^(-/-)mice were used as an experimental *** changes in liver tissue were monitored by hematoxylin and eosin ***,AST,glutathione,reactive oxygen species,and iron levels were measured using commercial ***-and pyroptosis-related protein and mRNA expression was detected by western blot and quantitative real-time polymerase chain ***1,p53,and GSDMD were assessed by immunofluorescence *** Serum AST and ALT levels were elevated in patients with ***1,solute carrier family 7a member 11(SLC7A11),and GPX4 protein expression was decreased and acetylated p5,p53,GSDMD,and acyl-CoA synthetase long-chain family member 4(ACSL4)protein levels were elevated in human ALF liver *** the p53 and ferroptosis inhibitor-treated and GSDMD^(-/-)groups,serum interleukin(IL)-1β,tumour necrosis factor alpha,IL-6,IL-2 and C-C motif ligand 2 levels were decreased and hepatic impairment was *** mice with GSDMD knockout,p53 was reduced,GPX4 was increased,and ferroptotic events(depletion of SLC7A11,elevation of ACSL4,and iron accumulation)were *** vitro,knockdown of p53 and overexpression of GPX
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