Linking stress-signaling, glutathione metabolism, signaling pathways and xenobiotic transporters.

摘要: Multi-specific drug-transport mechanisms are intricately involved in mediating a pleiotropic drug-resistance cancer cells by drug-accumulation defects which they over-expressed. The existence and over-expression drug-resistant neoplasms of transporter proteins belonging to ATP-binding cassette (ABC) family indicate that these myriad transporters contribute the multidrug-resistance phenomena removing or sequestering toxins metabolites. Another prominent mechanism multispecific involves glutathione linked enzymes, particularly those mercapturic acid pathway, metabolism excretion both endogenous exogenous electrophilic toxins. A key step efflux glutathione-electrophile conjugate has recently been shown be catalyzed largely stress-responsive protein RLIP76, splice variant peptide endowed human gene RALBP1. known involvement RLIP76 membrane signaling pathways endocytosis resulted new paradigm for transport related plays central role. Our recent studies demonstrating anti-apoptotic role demonstration dramatic response malignancies depletion targeting this pathway may highly effective multifaceted antineoplastic strategy.