Inactivation of cytosolic aldehyde dehydrogenase via S-nitrosylation in ethanol-exposed rat liver.
Aldehyde dehydrogenase (ALDH) isozymes are critically important in the metabolism of acetaldehyde, thus preventing its accumulation after ethanol-exposure. We previously reported that mitochondrial ALDH2 could be inactivated via S-nitrosylation in ethanol-exposed rats. This study was aimed at investigating whether cytosolic ALDH1, with a relatively-low-Km value (11-18 microM) for acetaldehyde, could be also inhibited in ethanol-exposed rats. Chronic or binge ethanol-exposure significantly decreased ALDH1 activity, which was restored by addition of dithiothreitol. Immunoblot analysis with the anti-S-nitroso-Cys antibody showed one immunoreactive band in the immunoprecipitated ALDH1 only from ethanol-exposed rats, but not from pair-fed controls, suggesting S-nitrosylation of ALDH1. Therefore inactivation of ALDH1 via S-nitrosylation can result in accumulation of acetaldehyde upon ethanol-exposure.
Laboratory of Membrane Biochemistry and Biophysics, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, 9000 Rockville pike, Bethesda, MD 20892-9410, USA.
Kwan-Hoon
KH
Moon
Mohamed A
MA
Abdelmegeed
Byoung-Joon
BJ
Song
D000079:Acetaldehyde / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D002492:Central Nervous System Depressants / Q000633:toxicity*; D003600:Cytosol / Q000201:enzymology* / Q000473:pathology; D004229:Dithiothreitol / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000473:pathology; D024101:Mitochondrial Proteins / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050697:Retinal Dehydrogenase
D002492:Central Nervous System Depressants; D007527:Isoenzymes; D024101:Mitochondrial Proteins; D000431:Ethanol; D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C505112:Aldh2 protein, rat; C523119:Aldh1a1 protein, rat; D050697:Retinal Dehydrogenase; D000079:Acetaldehyde; D004229:Dithiothreitol