Proteomics reveal a concerted upregulation of methionine metabolic pathway enzymes, and downregulation of carbonic anhydrase-III, in betaine supplemented ethanol-fed rats.
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.
Kharbanda
Kusum K
KK
Department of Veterans Affairs Medical Centre, Omaha, NE 68105, USA.
Vigneswara
Vasanthy
V
McVicker
Benita L
BL
Newlaczyl
Anna U
AU
Bailey
Kevin
K
Tuma
Dean
D
Ray
David E
DE
Carter
Wayne G
WG
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
D000431:Ethanol; D001622:Betaine; D008715:Methionine; D050904:Homocysteine S-Methyltransferase; D050938:Glycine N-Methyltransferase; D008716:Methionine Adenosyltransferase; D024403:Carbonic Anhydrase III