Genetic Variations in Nrf2-Keap1 Complex: A Step towards Understanding Cancer Resistance in Blind Mole Rats Cytotypes

Resumo

Abstract—The Nrf2-Keap1 regulation system plays a crucial role in cytoprotection against electrophilic/oxidative stress. Previous studies have identified missense mutations in Nrf2/Keap1 complex which abolish its activity. The amino acid corresponding to codon 212 in Keapl’s IVR domain is conserved as tyrosine (Y) among different mammalian species whereas only Nannospalax and two other species carry a cysteine (C) residue at this position. These species include Sperm whale and European hedgehog that live in hypoxic environment. In this study, we examined genetic variations in Nrf2-Keap1 complex, which was reported to be important in cancer pathogenesis in previous studies, in cancer resistant blind mole rat species with varying chromosome numbers (2n: 46–60) that we collected from different regions in Turkey. This study was the first to provide information on genetic variants in Nrf2/Keap1 complex of blind mole rats living in Turkey.