Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 30, Issue 9, Pages 992-999Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0891-5849(01)00491-9
Keywords
3-hydroxy-2-nonenal; pyruvate dehydrogenase complex; alpha-ketoglutarate dehydrogenase complex; branched-chain alpha-keto acid dehydrogenase complex; lipoyl compounds; lipoic acid plus; cysteine; glutathione; HepG2 cells; free radicals
Funding
- NIDDK NIH HHS [DK42885, DK20478, DK50430] Funding Source: Medline
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In the present study, the effects of 1-hydroxy-2-nonenal (HNE) on highly purified pyruvate dehydrogenase complex (PDC) and its catalytic components in vitro and on PDC, alpha -hetoglutarate dehydrogenase complex (KGDC), and the branched-chain alpha -keto acid dehydrogenase complex (BCKDC) activities in cultured human HepG2 cells were investigated. Among the PDC components, the activity of the dihydrolipoamide acetyltransferase-E3-binding protein subcomplex (E2-E3BP) only was decreased by HNE. Dihydrolipoamide dehydrogenase (E3) protected the E3-E3BP subcomplex from HNE inactivation in the absence of the substrates. In the presence of E3 and NADH, when lipoyl groups were reduced, higher inactivation of the E2-E3BP subcomplex by HNE was observed. Purified PDC was protected from HNE-induced inactivation by several thiol compounds including lipoic acid plus [LA-plus: 2-(N,N-dimethylamine)ethylamidolipoate HCl]. Treatment of cultured HepG2 cella with HNE resulted in a significant reduction of PDC and KGDC activities, whereas BCKDC activity decreased to a lesser extent. Lipoyl compounds afforded protection from HNE-induced inhibition of PDC. This protection was higher in the presence of cysteine and reduced glutathione. Cysteine was able to restore PDC activity to some extent after HNE treatment, These findings show that thiols, including lipoic acid, provide protection against HNE-induced inactivation of lipoyl-containing complexes; in the mitochondria. (C) 2001 Elsevier Science Inc.
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