The Roles of Stress-Activated Sty1 and Gcn2 Kinases and of the Protooncoprotein Homologue Int6/eIF3e in Responses to Endogenous Oxidative Stress during Histidine Starvation (original) (raw)

HepG2/C3A cells respond to cysteine deprivation by induction of the amino acid deprivation/integrated stress response pathway

Physiological Genomics, 2008

To further define genes that are differentially expressed during cysteine deprivation and to evaluate the roles of amino acid deprivation vs. oxidative stress in the response to cysteine deprivation, we assessed gene expression in human hepatoma cells cultured in complete or cysteine-deficient medium. Overall, C3A cells responded to cysteine deprivation by activation of the eukaryotic initiation factor (eIF)2α kinase-mediated integrated stress response to inhibit global protein synthesis; increased expression of genes containing amino acid response elements ( ASNS, ATF3, CEBPB, SLC7A11, and TRIB3); increased expression of genes for amino acid transporters ( SLC7A11, SLC1A4, and SLC3A2), aminoacyl-tRNA synthetases ( CARS), and, to a limited extent, amino acid metabolism ( ASNS and CTH); increased expression of genes that act to suppress growth ( STC2, FOXO3A, GADD45A, LNK, and INHBE); and increased expression of several enzymes that favor glutathione synthesis and maintenance of prot...

Protective Role of Histidine Supplementation Against Oxidative Stress Damage in the Management of Anemia of Chronic Kidney Disease

Pharmaceuticals

Anemia is a major health condition associated with chronic kidney disease (CKD). A key underlying cause of this disorder is iron deficiency. Although intravenous iron treatment can be beneficial in correcting CKD-associated anemia, surplus iron can be detrimental and cause complications. Excessive generation of reactive oxygen species (ROS), particularly by mitochondria, leads to tissue oxidation and damage to DNA, proteins, and lipids. Oxidative stress increase in CKD has been further implicated in the pathogenesis of vascular calcification. Iron supplementation leads to the availability of excess free iron that is toxic and generates ROS that is linked, in turn, to inflammation, endothelial dysfunction, and cardiovascular disease. Histidine is indispensable to uremic patients because of the tendency toward negative plasma histidine levels. Histidine-deficient diets predispose healthy subjects to anemia and accentuate anemia in chronic uremic patients. Histidine is essential in glo...