Generation of aldehyde-derived protein modifications in ethanol-exposed heart.
BACKGROUND
Although excessive ethanol consumption is known to lead to a variety of adverse effects in the heart, the molecular mechanisms of such effects have remained poorly defined. We hypothesized that posttranslational covalent binding of reactive molecular species to proteins occurs in the heart in response to acute ethanol exposure.


METHODS
The generation of protein adducts with several aldehydic species was examined by using monospecific antibodies against adducts with malondialdehyde (MDA), acetaldehyde (AA), MDA-AA hybrids, and hydroxyethyl radicals. Specimens of heart tissue were obtained from rats after intraperitoneal injections with alcohol (75 mmol/kg body weight) with or without pretreatment with cyanamide (0.05 mmol/kg body weight), an aldehyde dehydrogenase inhibitor.


RESULTS
The amounts of MDA and unreduced AA adducts were found to be significantly increased in the heart of the rats treated with ethanol, cyanamide, or both, whereas no other adducts were detected in statistically significant quantities. Immunohistochemical studies for characterization of adduct distribution revealed sarcolemmal adducts of both MDA and AA in the rats treated with ethanol and cyanamide in addition to intracellular adducts, which were also present in the group treated with ethanol alone.


CONCLUSIONS
These findings support the role of enhanced lipid peroxidation and the generation of protein-aldehyde condensates in vivo as a result of excessive ethanol intake. These findings may have implications in the molecular mechanisms of cardiac dysfunction in alcoholics.
Niemelä
Onni
O
Etela-Pohjanmaa Central Hospital Laboratory, Department of Clinical Chemistry and Institute of Medical Technology, University of Tampere, Finland. onni.niemela@epshp.fi
Parkkila
Seppo
S
Worrall
Simon
S
Emery
Peter W
PW
Preedy
Victor R
VR
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; D000431:Ethanol