Subcellular distribution and Nrf2/Keap1-interacting properties of Glutathione S-transferase P in hepatocellular carcinoma

• DOI: 10.1016/j.abb.2024.110043
• Publication Date: 2024-05-22T15:10:04Z
• Authors: Desirée Bartolini; Anna Maria Stabile; Anna Migni; Fabio Gurrado; Gessica Lioci; Francesca De Franco; Martina Mandarano; Gianluca Svegliat...; Manlio Di Cristina; Guido Bellezza; Mario Rende; Francesco Galli
• Keywords: Transferase; Glutathione S-transferase; Glutathione transferase; KEAP1

The oncogene and drug metabolism enzyme glutathione S-transferase P (GSTP) is also a GSH-dependent chaperone of signal transduction transcriptional proteins with key role in liver carcinogenesis. In this study, we explored GSTP hepatocellular carcinoma (HCC) investigating the possible interaction protein one its transcription factor metronome cancer cell redox, namely nuclear erythroid 2-related 2 (Nrf2). Expression, cellular distribution, function as glutathionylation GSTP1-1 isoform were investigated mouse model N-nitrosodiethylamine (DEN)-induced HCC vitro human lines. physical functional Nrf2 Keap1 by immunoprecipitation gene manipulation experiments. increased expression, enzymatic activity levels during DEN-induced tumor development mice; (PSSG) was masses. Higher preferential localization observed HepG2 Huh-7 hepatocarcinoma cells compared to HepaRG non-cancerous cells, along basal Ebselen-stimulated free GSH PSSG. inhibition analogue EZT induced apoptotic death cells. Hepatic c-Jun, two factors involved expression biosynthesis, DEN-HCC control animals; inhibitory β-TrCP oligomeric forms co-immunoprecipitated both Keap1. translocation transfection activation. conclusion, subcellular distribution are modified apparently contribute reprogramming redox type directly influencing system Nrf2/Keap1.