title: Immunoproteomic identification of biotransformed self-proteins from the livers of female Balb/c mice following chronic ethanol administration.
abstract: Chronic alcohol consumption culminates in alcoholic hepatitis which is characterized by ballooning degeneration of hepatocytes and perivenous inflammation. The aldehydes produced by ethanol oxidation and lipid peroxidation form adducts with the hepatic proteins rendering them immunogenic and initiating an autoimmune response. The present study was designed to identify these immunoreactive hepatic proteins in ethanol-treated Balb/c mice. Liver cytosolic, mitochondrial, and microsomal proteins from the ethanol-treated and control female Balb/c mice were size fractionated on SDS-PAGE and immunoblotted with the sera from the individual animal. The immunoreactive proteins were identified using antimouse IgG antibody and characterized by MALDI-TOF. It is the first report demonstrating that 15 hepatic proteins show immunoreactivity following alcohol administration. The identified autoreactive proteins ranged in function from metabolism to cytoskeletal support. Remarkably, three key enzymes of ethanol metabolism, namely alcohol dehydrogenase, aldehyde dehydrogenase I and III as well as important antioxidant enzyme glutathione S-transferase were found to be autoreactive upon ethanol treatment. We conclude that ethanol treatment induces biotransformation of host proteins from almost every compartment of the cell, especially the enzymes involved in the detoxification of ethanolic insult being the major target for biotransformation. Hence, we propose that these proteins can be the potential candidates for the biomarker studies.
authors.affiliation: Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India.
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Kaur
authors.forename: Anju
authors.initials: A
authors.lastname: Katyal
mesh_terms: D019342:Acetic Acid / Q000378:metabolism; D000818:Animals; D003600:Cytosol / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006519:Hepatitis, Alcoholic / Q000276:immunology / Q000378:metabolism*; D006651:Histocytochemistry; D015151:Immunoblotting; D008099:Liver / Q000737:chemistry* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008862:Microsomes, Liver / Q000737:chemistry / Q000201:enzymology; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D020543:Proteome / Q000032:analysis* / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D020543:Proteome; D000431:Ethanol; D008315:Malondialdehyde; D005978:Glutathione; D019342:Acetic Acid