Inactivation of cytosolic aldehyde dehydrogenase viaS‐nitrosylation in ethanol‐exposed rat liver

Abstract
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 viaS‐nitrosylation in ethanol‐exposed rats. This study was aimed at investigating whether cytosolic ALDH1, with a relatively‐low‐Kmvalue (11–18 μM) 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, suggestingS‐nitrosylation of ALDH1. Therefore inactivation of ALDH1 viaS‐nitrosylation can result in accumulation of acetaldehyde upon ethanol‐exposure.