title: NF-κB mediates the induction of Fas receptor and Fas ligand by microcystin-LR in HepG2 cells.
abstract: Microcystin-LR (MC-LR) is the most frequent and most toxic microcystin identified. This natural toxin has multiple features, including inhibitor of protein phosphatases 1 and 2A, inducer of oxidative stress, as well as, tumor initiator and promoter. One unique character of MC-LR is this chemical can accumulate into liver after contacting and lead to severe damage to hepatocytes, such as apoptosis. Fas receptor (Fas) and Fas ligand (FasL) system is a critical signaling system initiating apoptosis. In current study, we explored whether MC-LR could induce Fas and FasL expression in HepG2 cells, a well used in vitro model for the study of human hepatocytes. The data showed MC-LR induced Fas and FasL expression, at both mRNA and protein levels. We also found MC-LR induced apoptosis at the same incubation condition at which it induced Fas and FasL expression. The data also revealed MC-LR promoted nuclear translocation and activation of p65 subunit of NF-κB. By applying siRNA to knock down p65 in HepG2 cells, we successfully impaired the activation of NF-κB by MC-LR. In these p65 knockdown cells, we also observed significant reduction of MC-LR-induced Fas expression, FasL expression, and apoptosis. These findings demonstrate that the NF-κB mediates the induction of Fas and FasL as well as cellular apoptosis by MC-LR in HepG2 cells. The results bring important information for understanding how MC-LR induces apoptosis in hepatocytes.
authors.affiliation: Department of Pathology, Northwestern University, Chicago, IL 60613, USA. gong-feng@northwestern.edu
authors.forename: Gong
authors.initials: G
authors.lastname: Feng
authors.forename: Musa
authors.initials: M
authors.lastname: Abdalla
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Yansheng
authors.initials: Y
authors.lastname: Bai
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D053222:Fas Ligand Protein / Q000096:biosynthesis*; D005434:Flow Cytometry; D055785:Gene Knockdown Techniques; D006801:Humans; D020287:In Situ Nick-End Labeling; D008387:Marine Toxins; D052998:Microcystins / Q000494:pharmacology*; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019014:fas Receptor / Q000096:biosynthesis*
chemical_list: D017931:DNA Primers; D053222:Fas Ligand Protein; D008387:Marine Toxins; D052998:Microcystins; D016328:NF-kappa B; D019014:fas Receptor; C057862:cyanoginosin LR