Ralbp1 in stress resistance

Ralbp11 is a multi-specific transporter of glutathione conjugates as well as unconjugated amphiphilic toxins. Because glutathione conjugates are major metabolites of toxic lipid peroxidation products generated as a consequence of oxidant and radiant stress, the hypothesis is put forth that the function of Ralbp1 in-vivo and in vitro should be to protect organisms from chemical stress by removing toxic chemicals. Studies described in this dissertation were designed to prove this hypothesis. We tested the hypothesis by examining whether the inhibition or augmentation of Ralbp1 would sensitize or protect cells and whole animals from the toxic effects of chemicals and radiation. These studies establish that Ralbp1 is a primary determinant of resistance to chemical stressors by the direct transport of these toxins.;1The human gene RALBP1 (18p 11.22) encodes a splice-variant designated RLIP76 when it was originally cloned through yeast two-hybrid method as the first known Ral effector by Julien-Flores et al. (Flores 2003). The corresponding animal genes from rat (Ralbp1, Ral-binding protein-1) and mouse (Rip1, Ral-interacting protein-1) encode a splice variant protein homologous to RLIP76, designated Ralbp1 (also written as RalBP1). For the purpose of this manuscript, we will use Ralbp1 to refer to the 76 kDa splice variant protein, and RALBP1 when referring to the gene.