Metabolic regulation of aldose reductase activity by nitric oxide donors

Bharat L. Dixit, Kota V. Ramana, Deepak Chandra, Elias B. Jackson, Sanjay Srivastava, Aruni Bhatnagar, Satish K. Srivastava

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Regulation of aldose reductase (AR), a member of the aldo-keto reductase superfamily, by nitric oxide (NO) donors was examined. Incubation of human recombinant AR with S-nitrosoglutathione (GSNO) led to inactivation of the enzyme and the formation of an AR-glutathione adduct. In contrast, incubation with S-nitroso-N-acetyl penicillamine (SNAP) or N-(β-D-glucopyranosyl)-SNAP (GlycoSNAP) led to an increase in enzyme activity which was accompanied by the direct nitrosation of the enzyme and the formation of a mixed disulfide with the NO-donor. To examine in vivo modification, red blood cells (RBC) and rat aortic vascular smooth muscle cells (VSMC) were incubated with 1 mM GSNO or SNAP. Exposure of VSMC to SNAP and GSNO for 2 h at 37°C led to ∼71% decrease in the enzyme activity with DL-glyceraldehyde as the substrate. Similarly, exposure of RBC in 5 mM glucose to NO-donors for 30 min at room temperature, followed by increasing the glucose concentration to 40 mM, resulted in >75% decrease in the formation of sorbitol. These investigations indicate that NO and/or its bioactive metabolites can regulate cellular AR, leading to either activation (by nitrosation) or inactivation (by S-thiolation).

Original languageEnglish (US)
Pages (from-to)573-581
Number of pages9
JournalChemico-Biological Interactions
Volume130-132
DOIs
StatePublished - Jan 30 2001

Keywords

  • Aldose reductase
  • Nitric oxide
  • Red blood cells
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Toxicology

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    Dixit, B. L., Ramana, K. V., Chandra, D., Jackson, E. B., Srivastava, S., Bhatnagar, A., & Srivastava, S. K. (2001). Metabolic regulation of aldose reductase activity by nitric oxide donors. Chemico-Biological Interactions, 130-132, 573-581. https://doi.org/10.1016/S0009-2797(00)00300-8