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LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity.
Am J Physiol Cell Physiol. 2004 Aug; 287(2):C508-16.AJ

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 transcriptional activators of these genes that facilitates cellular protection against ethanol stress and plays a role in RA production.

Authors+Show Affiliations

Department of Ophthalmology, 985840 Nebraska Medical Center, University of Nebraska Medical Center, Omaha, NE 68198-5840, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15238362

Citation

Fatma, Nigar, et al. "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, vol. 287, no. 2, 2004, pp. C508-16.
Fatma N, Kubo E, Chylack LT, et al. LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity. Am J Physiol, Cell Physiol. 2004;287(2):C508-16.
Fatma, N., Kubo, E., Chylack, L. T., Shinohara, T., Akagi, Y., & Singh, D. P. (2004). 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, 287(2), C508-16.
Fatma N, et al. LEDGF Regulation of Alcohol and Aldehyde Dehydrogenases in Lens Epithelial Cells: Stimulation of Retinoic Acid Production and Protection From Ethanol Toxicity. Am J Physiol, Cell Physiol. 2004;287(2):C508-16. PubMed PMID: 15238362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - LEDGF regulation of alcohol and aldehyde dehydrogenases in lens epithelial cells: stimulation of retinoic acid production and protection from ethanol toxicity. AU - Fatma,Nigar, AU - Kubo,Eri, AU - Chylack,Leo T,Jr AU - Shinohara,Toshimichi, AU - Akagi,Yoshio, AU - Singh,Dhirendra P, PY - 2004/7/9/pubmed PY - 2004/8/25/medline PY - 2004/7/9/entrez SP - C508 EP - 16 JF - American journal of physiology. Cell physiology JO - Am. J. Physiol., Cell Physiol. VL - 287 IS - 2 N2 - 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 transcriptional activators of these genes that facilitates cellular protection against ethanol stress and plays a role in RA production. SN - 0363-6143 UR - https://www.unboundmedicine.com/medline/citation/15238362/LEDGF_regulation_of_alcohol_and_aldehyde_dehydrogenases_in_lens_epithelial_cells:_stimulation_of_retinoic_acid_production_and_protection_from_ethanol_toxicity_ L2 - http://www.physiology.org/doi/full/10.1152/ajpcell.00076.2004?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -