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- Title
Differential cytoprotection by glycine against oxidant damage to proximal tubule cells.
- Authors
Sogabe, Keizo; Roeser, Nancy F.; Venkatachalam, Manjeri A.; Weinberg, Joel M.
- Abstract
Tert-butyl hydroperoxide (tBHP) injured freshly isolated proximal tubules in an Fe-dependent fashion that was ameliorated by a lipophilic antioxidant, diphenyl-p-phenylenediamine (DPPD), but was only minimally affected by glycine. Menadione-inducted injury was Fe-independent and was unaffected by DPPD, but was strongly blocked by glycine. Fe was highly toxic when intracellular loading was facilitated by concomitant treatment with hydroxyquinoline (HO). This toxicity was blocked by DPPD or chelating the Fe, but not by glycince. All of the lesions were characterized by severe depletion of glutathione and other soluble thiols. Menadione induced large increases in protein associated with the Triton-insoluble cytoskeleton and decreases in protein thiol content, consistent with extensive cross linking, but did not increase thioharbituric acid reactive substances (TBARS). tBHP and HQ + Fe had either no effect or only moderate, delayed effects on cytoskeletal proteins, but induced substantial increases of TBARS. Glycine did not the alter changes in cytoskeletal proteins, thiols, or TBARS produced by any of the agents. Protection against tBHP toxicity by deferoxamine and DPPD was accompanied by substantial suppression of TBARS accumulation. Superimposition of hypoxia during tBMP exposure reduced TBARS accumulation and restored cytoprotective activity to glycine. Thus, in contrast to its consistently strong cyloprotection against a number of other insults, glycine is only variably cytoprotective against oxidant lesions in freshly isolated proximal tubules. Extensive oxidative crosslinking of proteins is compatible with maintenance of glycine cytoprotection against lethal membrane damage. Fe-induced injury to proximal tubules associated with lipid peroxidation as manifested by TBARS formation is a relatively glycine-insensitive insult.
- Subjects
GLYCINE; KIDNEY tubules; OXIDIZING agents; AMINO acid neurotransmitters; HYDROXYQUINOLINE; DEFEROXAMINE; MICROBIAL metabolites; CYTOSKELETAL proteins
- Publication
Kidney International, 1996, Vol 50, Issue 3, p845
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1996.384