Detection and localization of protein-acetaldehyde adducts in rat brain after chronic ethanol treatment.
BACKGROUND
Ethanol is metabolized to acetaldehyde in the cell, which is potentially deleterious because it can react with cellular proteins and form protein-acetaldehyde adducts, which can interfere with normal cellular function. Because the primary site of ethanol action is the brain, the present study was carried out to determine whether protein-acetaldehyde adducts are formed in rat brain after chronic ethanol administration.


METHODS
Rats were treated with ethanol for 1 year, and the formation of protein-acetaldehyde adducts was examined by immunoblot analysis and localized in brain by immunohistochemical analysis by using affinity purified antibody to acetaldehyde-hemocyanin adduct.


RESULTS
In the brain of rats administered ethanol for up to 1 year, protein-acetaldehyde adducts were detectable by immunoblot analysis. In brain, mitochondria was the primary site of adduct formation, unlike the liver, where the major protein-acetaldehyde adduct has been detected in the cytosol. Immunohistochemical localization of protein-acetaldehyde adducts in chronic ethanol-treated rat brain demonstrated the selective presence of adducts in cortical neurons, granule cell layer of dentate gyrus, neurons in the midbrain, and granular cell layers of cerebellum.


CONCLUSIONS
These results demonstrate the significant formation of protein-acetaldehyde adducts in rat brain after ethanol ingestion. The modification of mitochondrial proteins in brain by protein-acetaldehyde adduct formation is significant because mitochondrial dysfunction has been implicated in neurodegeneration.
Upadhya
Sudarshan C
SC
Department of Neurochemistry, National Institute of Mental Health and Neurosciences, Bangalore, India.
Ravindranath
Vijayalakshmi
V
D000079:Acetaldehyde / Q000032:analysis* / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D011506:Proteins / Q000032:analysis* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000737:chemistry / Q000378:metabolism
D011506:Proteins; D000431:Ethanol; D000079:Acetaldehyde