Korean J Physiol Pharmacol.  2001 Jun;5(3):271-278.

Effects of oxidative stress on the expression of aldose reductase in vascular smooth muscle cells

• Kim HJ
• Chang KC
• Seo HG

Abstract

Oxidative stress and methylglyoxal (MG), a reactive dicarbonyl metabolites produced by enzymatic and non-enzymatic reaction of normal metabolism, induced aldose reductase (AR) expression in rat aortic smooth muscle cells (SMC). AR expression was induced in a time-dependent manner and reached at a maximum of 4.5-fold in 12 h of MG treatment. This effect of MG was completely abolished by cyclohemide and actinomycin D treatment suggesting AR was synthesized by de novo pathway. Pretreatment of the SMC with N-acetyl-L-cysteine significantly down-regulated the MG-induced AR mRNA. Furthermore, DL-Buthionine-(S,R)-sulfoximine, a reagent which depletes intracellular glutathione levels, increased the levels of MG-induced AR mRNA. These results indicated that MG induces AR mRNA by increasing the intracellular peroxide levels. Aminoguanidine, a scanvenger of dicarbonyl, significantly down-regulated the MG-induced AR mRNA. In addition, the inhibition of AR activities with statil, an AR inhibitor, enhanced the cytotoxic effect of MG on SMC under normal glucose, suggesting a protective role of AR against MG-induced cell damages. These results imply that the induction of AR by MG may contribute to an important cellular detoxification of reactive aldehyde compounds generated under oxidative stress in extrahepatic tissues.

MeSH Terms

Acetylcysteine
Aldehyde Reductase*
Animals
Dactinomycin
Glucose
Glutathione
Metabolism
Muscle, Smooth, Vascular*
Myocytes, Smooth Muscle
Oxidative Stress*
Pyruvaldehyde
Rats
RNA, Messenger
Acetylcysteine
Aldehyde Reductase
Dactinomycin
Glucose
Glutathione
Pyruvaldehyde
RNA, Messenger