title: Proteomics reveal a concerted upregulation of methionine metabolic pathway enzymes, and downregulation of carbonic anhydrase-III, in betaine supplemented ethanol-fed rats.
abstract: We employed a proteomic profiling strategy to examine the effects of ethanol and betaine diet supplementation on major liver protein level changes. Male Wistar rats were fed control, ethanol or betaine supplemented diets for 4 weeks. Livers were removed and liver cytosolic proteins resolved by one-dimensional and two-dimensional separation techniques. Significant upregulation of betaine homocysteine methyltransferase-1, methionine adenosyl transferase-1, and glycine N-methyltransferase were the most visually prominent protein changes observed in livers of rats fed the betaine supplemented ethanol diet. We hypothesise that this concerted upregulation of these methionine metabolic pathway enzymes is the protective mechanism by which betaine restores a normal metabolic ratio of liver S-adenosylmethionine to S-adenosylhomocysteine. Ethanol also induced significant downregulation of carbonic anhydrase-III protein levels which was not restored by betaine supplementation. Carbonic anhydrase-III can function to resist oxidative stress, and we therefore hypothesise that carbonic anhydrase-III protein levels compromised by ethanol consumption, contribute to ethanol-induced redox stress.
authors.affiliation: Department of Veterans Affairs Medical Centre, Omaha, NE 68105, USA.
authors.forename: Kusum K
authors.initials: KK
authors.lastname: Kharbanda
authors.forename: Vasanthy
authors.initials: V
authors.lastname: Vigneswara
authors.forename: Benita L
authors.initials: BL
authors.lastname: McVicker
authors.forename: Anna U
authors.initials: AU
authors.lastname: Newlaczyl
authors.forename: Kevin
authors.initials: K
authors.lastname: Bailey
authors.forename: Dean
authors.initials: D
authors.lastname: Tuma
authors.forename: David E
authors.initials: DE
authors.lastname: Ray
authors.forename: Wayne G
authors.initials: WG
authors.lastname: Carter
mesh_terms: D000818:Animals; D001622:Betaine / Q000008:administration & dosage*; D024403:Carbonic Anhydrase III / Q000378:metabolism; D015536:Down-Regulation; D000431:Ethanol / Q000037:antagonists & inhibitors / Q000633:toxicity*; D050938:Glycine N-Methyltransferase / Q000378:metabolism; D050904:Homocysteine S-Methyltransferase / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D008716:Methionine Adenosyltransferase / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation
chemical_list: D000431:Ethanol; D001622:Betaine; D008715:Methionine; D050904:Homocysteine S-Methyltransferase; D050938:Glycine N-Methyltransferase; D008716:Methionine Adenosyltransferase; D024403:Carbonic Anhydrase III