Metabolic regulation of aldose reductase activity by nitric oxide donors.
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-(beta-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 degrees C led to approximately 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).
Dixit
B L
BL
Departments of Human Biological Chemistry and Genetics, University of Texas Medical Branch, 619 Basic Science Building, 77555-0647, Galveston, TX, USA.
Ramana
K V
KV
Chandra
D
D
Jackson
E B
EB
Srivastava
S
S
Bhatnagar
A
A
Srivastava
S K
SK
D000449:Aldehyde Reductase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009603:Nitroso Compounds / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D026422:S-Nitrosoglutathione; D021241:Spectrometry, Mass, Electrospray Ionization
D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011994:Recombinant Proteins; C110881:S-nitro-N-acetylpenicillamine; D026422:S-Nitrosoglutathione; D000449:Aldehyde Reductase; D005978:Glutathione; D010396:Penicillamine