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Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide‐mediated S ‐nitrosylation
Author(s) -
Moon Kwan-Hoon,
Kim Bong-Jo,
Song Byoung J.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.09.082
Subject(s) - aldh2 , peroxynitrite , nitrite , nitric oxide , chemistry , aldehyde dehydrogenase , s nitrosoglutathione , s nitrosylation , acetaldehyde , glutathione , biochemistry , nitrosylation , microbiology and biotechnology , enzyme , cysteine , biology , superoxide , nitrate , organic chemistry , ethanol
Mitochondrial aldehyde dehydrogenase (ALDH2) is responsible for the metabolism of acetaldehyde and other toxic lipid aldehydes. Despite many reports about the inhibition of ALDH2 by toxic chemicals, it is unknown whether nitric oxide (NO) can alter the ALDH2 activity in intact cells or in vivo animals. The aim of this study was to investigate the effects of NO on ALDH2 activity in H4IIE‐C3 rat hepatoma cells. NO donors such as S ‐nitrosoglutathione (GSNO), S ‐nitroso‐ N ‐acetylpenicillamine, and 3‐morpholinosydnonimine significantly increased the nitrite concentration while they inhibited the ALDH2 activity. Addition of GSH‐ethylester (GSH‐EE) completely blocked the GSNO‐mediated ALDH2 inhibition and increased nitrite concentration. To directly demonstrate the NO‐mediated S ‐nitrosylation and inactivation, ALDH2 was immunopurified from control or GSNO‐treated cells and subjected to immunoblot analysis. The anti‐nitrosocysteine antibody recognized the immunopurified ALDH2 only from the GSNO‐treated samples. All these results indicate that S ‐nitrosylation of ALDH2 in intact cells leads to reversible inhibition of ALDH2 activity.