LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity

American Journal of Physiology. Cell Physiology
Nigar FatmaDhirendra P Singh

Abstract

Retinoic acid (RA) is required for the normal growth and maintenance of many cell types, including lens epithelial cells (LECs). Alcohol (ADH) and aldehyde (ALDH) dehydrogenases are implicated in cellular detoxification and conversion of vitamin A to RA. Lens epithelium-derived growth factor (LEDGF) provides cellular protection against stress by transactivating stress-associated genes. Here we show evidence that LEDGF binds and transactivates heat shock (nGAAn) and stress response (A/TGGGGA/T) elements in the promoters of ADH1, ADH4, and retinaldehyde 2 (RALDH2) genes. Electrophoretic mobility and supershift assays disclosed specific binding of LEDGF to nGAAn and A/TGGGGA/T elements in these gene promoters. Transfection experiments in LECs with promoters linked to a chloramphenicol acetyltransferase (CAT) reporter gene along with LEDGF cDNA revealed higher CAT activity. RT-PCR results confirmed that LECs overexpressing LEDGF contained increased levels of ADH1, ADH4, and RALDH2 mRNA. Notably, LECs displayed higher LEDGF mRNA and protein expression during ethanol stress. Cells overexpressing LEDGF typically exhibited elevated RA levels and survived well during ethanol stress. The present findings indicate that LEDGF is one of the...Continue Reading

References

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Citations

Aug 19, 2008·Molecular Cancer Research : MCR·Terry A Brown-BryanCarlos A Casiano
Jun 30, 2012·EMBO Molecular Medicine·Anya Rudnicki, Karen B Avraham
Jul 10, 2008·Expert Opinion on Drug Metabolism & Toxicology·Satori A MarchittiVasilis Vasiliou
Oct 24, 2006·Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society·Aurea Navarro-SabatéRamon Bartrons
Jan 13, 2006·American Journal of Physiology. Cell Physiology·Yoshihiro TakamuraDhirendra P Singh

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