Detoxification of lipid peroxidation product, 4-hydroxynonenal by aldose reductase

S. Srivastava, A. Chandra, Naseem Ansari, A. Bhatnagar, Satish Srivastava

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Abstract

β-scission of alkoxy radicals leads to the formation of oxocompounds such as 4-hydroxynonenal (HNE), which could act as "toxic second messenger" and potentiate cellular injury, under oxidative stress. HNE, conjugates with GSH spontaneously or catalyzed by glutathione-Stransferases. We have demonstrated that homogenous preparation of heart and lens aldose reductase (AR) efficiently reduces HNE and HNE-GS in the presence of NADPH (Km HNE approximately 8 μM and Km HNE-GS approximately 30 μM). In the absence of NADPH, HNE causes a time and concentration-dependent inactivation of AR and more than 10 fold increase in Km HNE along with increase in IC50 from 2 μM to 1000 nM. The HNE modified enzyme also loses the sensitivity to sulfate. Amino acid sequence analysis showed that with incubations of reduced AR with 4-3H-HNE resulted in covalent modification of Cys-187 and Cys-298. Since aldehyde reductase, alcohol dehydrogenase, and aldehyde oxidases are poorly expressed in the heart, detoxification of alkenals and their conjugates with GSH by AR may represent an important secondary antioxidative defense mechanism of cardio protection against oxidative stress.

Original languageEnglish (US)
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Srivastava, S., Chandra, A., Ansari, N., Bhatnagar, A., & Srivastava, S. (1996). Detoxification of lipid peroxidation product, 4-hydroxynonenal by aldose reductase. FASEB Journal, 10(3).