4-hydroxy-2,3-trans-nonenal induces transcription and expression of aldose reductase.

Treatment of A7r5 rat vascular smooth muscle cells with 4-hydroxy-2,3-trans-nonenal (HNE) resulted in increased aldose reductase mRNA transcription. Induction was time dependent, reaching a maximum (2,3-fold) after 7 hours. An enzymatically active aldose reductase analysed by Western blotting and enzyme assays was expressed. Sorbinil, an aldose reductase inhibitor, induced a significant enhancement of HNE cytotoxicity, indicating a protective role of aldose reductase against HNE-induced A7r5 cell death. These data indicate that induction of aldose reductase by HNE may represent an important cellular defence mechanism against oxidative injury.