Possible role of cysteine-S-conjugate β-lyase in species differences in cisplatin nephrotoxicity.

Abstract

To better understand species differences in cisplatin nephrotoxicity, we focused on renal cysteine-S-conjugate β-lyase (C-S lyase), which may play a crucial role in the metabolism of platinum (Pt)-cysteine conjugates. Aminooxyacetic acid hemihydrochloride (AOAA), an inhibitor of C-S lyase, reduced renal injuries due to cisplatin in rats, suggesting involvement of C-S lyase. On day 5 following a bolus cisplatin injection, three species showed in vivo nephrotoxic potentials in the order of rats>mice=rabbits (the highest to lowest), based on body surface. The levels of renal Pt residue at the nephrotoxic dose were in order of rabbits>rats>mice. Meanwhile, the activity of endogenous (basal) mitochondrial aspartate aminotransferase (AST), one of the C-S lyases, in the renal cortex of naive animals was rats>mice=rabbits. In a qualitative Western blot analysis, expression of mitochondrial C-S lyase in the kidney was observed at approximately 37kDa in all five species used. In in vitro studies, the cytotoxicity of cisplatin was dependent on the expression level of C-S lyase mRNA in the respective renal cells. These results demonstrate that species differences in cisplatin nephrotoxicity are attributable to an interaction of renal Pt transition with C-S lyase activity.

• Authors: Rieko Katayama, Saori Nagata, Hiroko Iida, Norio Yamagishi, Tetsuro Yamashita, Kazuhisa Furuhama
• Journal: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association (Food Chem Toxicol) Vol. 49 Issue 9 Pg. 2053-9 (Sep 2011) ISSN: 1873-6351 [Electronic] England
• PMID: 21640784 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Elsevier Ltd. All rights reserved.

Chemical References

• Antineoplastic Agents
• DNA Primers
• RNA, Messenger
• Carbon-Sulfur Lyases
• cysteine-S-conjugate beta-lyase
• Cisplatin

Topics

• Animals
• Antineoplastic Agents (toxicity)
• Base Sequence
• Blotting, Western
• Carbon-Sulfur Lyases (genetics, metabolism)
• Cell Line
• Cisplatin (toxicity)
• DNA Primers
• Dogs
• Kidney (drug effects)
• Mice
• RNA, Messenger (genetics)
• Rabbits
• Rats
• Real-Time Polymerase Chain Reaction
• Species Specificity