title: PDIA3 Knockdown Exacerbates Free Fatty Acid-Induced Hepatocyte Steatosis and Apoptosis.
abstract: Nonalcoholic fatty liver disease (NAFLD) has emerged as one of the most common chronic liver disease over the past decades. Endoplasmic reticulum stress (ERS) plays a pivotal role during the development of NAFLD. This study aims to analyze the potential role of protein disulfide isomerase A3 precursor (PDIA3), one of the ER chaperones, in free fatty acid-induced cell model of NAFLD. Human liver L02 cell line was treated with sodium palmitate for 24 hours, which developed severe intracellular lipid accumulation. The increased protein level of PDIA3 was detected via immunoblotting analysis in the fat loaded cell models of NAFLD. siRNA-mediated knockdown of PDIA3 in L02 cells not only increased the cellular lipid accumulation, but also exacerbated hepatocytes apoptosis induced by sodium palmitate. Further investigation revealed that knockdown of PDIA3 up-regulated protein expression of fatty acid synthase (FAS), a key enzyme involved in fatty acid synthesis. PDIA3 knockdown also up-regulated key molecules of ERS pathway, including glucose-regulated protein 78 (GRP78), phospho-PKR-like ER kinase (p-PERK), and C/EBP homologous protein (CHOP). Our results suggested that ER chaperone PDIA3 plays a pivotal role in FFA-induced hepatocyte steatosis and apoptosis.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: Xue-qun
authors.initials: XQ
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: Chao-hui
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: Cheng-fu
authors.initials: CF
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, Ningbo No.1 Hospital, Ningbo, Zhejiang Province, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: You-ming
authors.initials: YM
authors.lastname: Li
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hang Zhou, Zhejiang Province, China.
authors.forename: Wei-xing
authors.initials: WX
authors.lastname: Chen
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids / Q000633:toxicity*; D005234:Fatty Liver / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D055785:Gene Knockdown Techniques; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D019704:Protein Disulfide-Isomerases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D005227:Fatty Acids; C000717247:HSPA5 protein, human; D019704:Protein Disulfide-Isomerases; C085868:PDIA3 protein, human