title: Aldose reductase prevents aldehyde toxicity in cultured human lens epithelial cells.
abstract: Aldehydes are widespread environmental and industrial compounds, which cause cytotoxicity, tissue damage, mutagenicity, and carcinogenicity leading to various disease conditions such as cardiovascular, bronchial, and visual complications. We have shown earlier that aldose reductase (AR) besides reducing glucose to sorbitol, efficiently reduces various toxic lipid-derived aldehydes, generated under oxidative stress, with K(m) in the physiological range. We have identified the role of AR in the prevention of various lipid aldehyde-induced cytotoxic signals leading to apoptosis in human lens epithelial cells (HLEC). HLEC were cultured without or with AR inhibitors followed by addition of various saturated and unsaturated lipid aldehydes with a carbon chain length varying from C3 to C10. The cell viability was assessed by cell counts and MTT assay, and apoptosis was measured by evaluating nucleosomal degradation and caspase-3 activation using specific ELISA kits. Although all the aldehydes caused apoptosis of HLEC, the unsaturated aldehydes were more toxic than saturated aldehydes. Inhibition of AR by sorbinil potentiated while the over-expression of AR prevented the apoptosis induced by various lipid aldehydes. AR over-expression also prevented the lipid aldehyde-induced activation of caspase-3, MAPK, JNK and the expression of Bcl-2 family of proteins in HLEC. The results indicate that the lipid aldehydes generated under oxidative stress are cytotoxic to HLEC leading to apoptosis and that the reduction of lipid aldehydes by AR would prevent it.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, 301 University Blvd., 6.644 Basic Science Bldg., Galveston, TX 77555-0647, USA.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Pladzyk
authors.forename: Kota V
authors.initials: KV
authors.lastname: Ramana
authors.forename: Naseem H
authors.initials: NH
authors.lastname: Ansari
authors.forename: Satish K
authors.initials: SK
authors.lastname: Srivastava
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000447:Aldehydes / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000633:toxicity*; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D048289:Imidazolidines / Q000494:pharmacology; D007908:Lens, Crystalline / Q000201:enzymology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018384:Oxidative Stress; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D000447:Aldehydes; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D048289:Imidazolidines; D019253:Proto-Oncogene Proteins c-bcl-2; D000449:Aldehyde Reductase; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; C026411:sorbinil