title: Peroxiredoxin 6 attenuates ischemia‑ and hypoxia‑induced liver damage of brain‑dead donors.
abstract: Oxidative stress induced by ischemia and hypoxia in the livers of donors after brain death (DBD) is associated with poor organ function and low patient survival rates in those receiving DBD liver transplants. Peroxiredoxin 6 (Prdx6) can defend cells against liver damage induced by oxidative stress. The present study aimed to investigate the role of Prdx6 in ischemia‑ and hypoxia‑induced liver damage in DBD livers. Liver tissue samples from ten DBD patients were collected. The control group constituted of six liver samples from patients with liver hemangioma that had accepted tumor excision surgery. Protein expression levels were determined by western blotting, cell viability was assessed using a CCK‑8 assay, intracellular reactive oxygen species (ROS) levels were measured using a ROS assay kit, and phospholipase A2 (PLA2) activity was measured using a PLA2 assay kit. In DBD liver samples, Prdx6 expression was downregulated and the nuclear factor‑κB (NF‑κB) signaling pathway was activated. Furthermore, when human liver L02 cells were exposed to ischemia and hypoxia, the expression of Prdx6 was reduced, causing an increase in reactive oxygen species (ROS); this in turn activated NF‑κB signaling and lowered cell viability (P<0.01). In agreement, overexpression of Prdx6 reduced ROS levels and improved cell viability. It was also demonstrated that inhibition of NF‑κB increased Prdx6 expression, while inhibition of Prdx6 limited PLA2 activity, exacerbating ischemia‑ and hypoxia‑induced cell damage. This data suggests that Prdx6 and its PLA2 activity have a protective role in DBD livers, the expression of which is regulated by NF‑κB. Thus, Prdx6 may be a novel target to alleviate liver damage in DBD.
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Tu
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fan
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Qiao
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xia
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Long
authors.initials: L
authors.lastname: Hu
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Guizhu
authors.initials: G
authors.lastname: Peng
authors.affiliation: Institute of Hepatobiliary Diseases of Wuhan University, Transplant Center of Wuhan University, Hubei Key Laboratory of Medical Technology on Transplantation, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, P.R. China.
authors.forename: Qifa
authors.initials: Q
authors.lastname: Ye
mesh_terms: D015153:Blotting, Western; D001926:Brain Death / Q000473:pathology*; D002460:Cell Line; D019610:Cytoprotection / Q000187:drug effects; D005994:Glycerophosphates / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000150:complications / Q000473:pathology*; D042541:Intracellular Space / Q000378:metabolism; D007511:Ischemia / Q000150:complications / Q000473:pathology*; D008099:Liver / Q000187:drug effects / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D054465:Peroxiredoxin VI / Q000378:metabolism*; D064801:Phospholipase A2 Inhibitors / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014019:Tissue Donors; D014162:Transfection
chemical_list: D005994:Glycerophosphates; D016328:NF-kappa B; D064801:Phospholipase A2 Inhibitors; D017382:Reactive Oxygen Species; C078587:1-hexadecyl-3-trifluoroethylglycero-sn-2-phosphomethanol; C515977:PRDX6 protein, human; D054465:Peroxiredoxin VI; D054467:Phospholipases A2