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Aldose reductase induction: a novel response to oxidative stress of smooth muscle cells
Author(s) -
Spycher Stefan E.,
TabatabaVakili Shirin,
O'Donnell Valerie B.,
Palomba Letizia,
Azzi Angelo
Publication year - 1997
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.11.2.9039961
Subject(s) - aldose reductase , sorbinil , aldose reductase inhibitor , aldehyde reductase , oxidative stress , biochemistry , chemistry , catalase , reductase , lipid peroxidation , enzyme
Hydrogen peroxide (H 2 O 2 ) or 4‐hy‐droxy‐2,3‐ trans ‐nonenal (HNE) treatment of rat vascular smooth muscle cells (A7r5) caused induction of aldose reductase mRNA. Induction was dose (10‐100 μM H 2 O 2 , 1‐10 μM HNE) and time dependent, reaching a maximum (three‐ to fourfold) after 7‐12 h. Treatment of cells with actinomycin D confirmed de novo synthesis of aldose reductase mRNA. H 2 O 2 ‐induced expression was prevented by catalase but unaffected by Desferal, indicating that metal catalyzed degradation of peroxide was not involved. Induction of enzymatic ally active aldose reductase by H 2 O 2 and HNE was confirmed using Western blotting and enzyme assays. Aldose reductase can metabolize several aldehyde compounds including HNE, a major toxic product of lipid peroxidation. Inclusion of Sorbinil, an aldose reductase inhibitor, in toxicity assays resulted in a significant (twofold) enhancement of HNE‐mediated killing of A7r5 cells, suggesting a protective role of aldose reductase against HNE‐induced cell death. These data indicate that the induction of aldose reductase during oxidative stress might represent an important cellular antioxidant defense mecha‐nism.—Spycher, S. E., Tabataba‐Vakili, S., O'Don‐nell, V. B., Palomba, L., and Azzi, A. Aldose reductase induction: a novel response to oxidative stress of smooth muscle cells. FASEB J. 11, 181‐188 (1997)