ATP7B R778L mutant hepatocytes resist copper toxicity by activating autophagy and inhibiting necroptosis.

ABSTRACT: Wilson's disease (WD) is an inherited disease characterized by copper metabolism disorder caused by mutations in the adenosine triphosphatase copper transporting β gene (ATP7B). Currently, WD cell and animal model targeting the most common R778L mutation in Asia is lacking. In addition, the mechanisms by which hepatocytes resist copper toxicity remain to be further elucidated. In this study, we aimed to construct a novel WD cell model with R778L mutation and dissected the molecular basics of copper resistance. A novel HepG2 cell line stably expressing the ATP7B R778L gene (R778L cell) was constructed. The expression of necroptosis- and autophagy-related molecules was detected by PCR and Western blot (WB) in wild-type (WT) HepG2 and R778L cells with or without CuSO₄ treatment. In

SUBMITTER: Tang S 

PROVIDER: S-EPMC10505209 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature