Age-related effects of methionine-enriched diet on plasma homocysteine concentration and methylation of hepatic DNA in rats.
In the present study we determined the age-related effect of methionine-enriched diet, a model of hyperhomocysteinemia, on the level of plasma homocysteine and hepatic global DNA methylation in rats. Feeding methionine diet to middle-aged rats for only 14 days resulted in a significant increase in plasma homocysteine level and DNA hypomethylation. In contrast, feeding the methionine-containing diet for 2 weeks to juvenile or post-pubertal animals did not alter the level of plasma homocysteine or hepatic DNA methylation. Supplementation of the methionine-enriched diet with vitamins B6, B12 and folic acid prevented both hepatic DNA hypomethylation and an increase of plasma homocysteine concentration in the middle-aged rats. These findings indicate that the elevated level of plasma homocysteine may be indicative of much broader and deeper alterations in intracellular methylation dysfunction, and suggest that dietary enrichment with B-vitamins is essential for the metabolism of homocysteine, especially in adult animals.
Division of Biochemical Toxicology, National Center for Toxicological Research, Jefferson, USA. ipogribny@nctr.fda.gov
I P
IP
Pogribny
T V
TV
Prizimirska
G I
GI
Kulik
M B
MB
Lutsiuk
O O
OO
Pentiuk
K P
KP
Postovitenko
M A
MA
Artemchuk
L A
LA
Poirier
V F
VF
Chekhun
D000375:Aging / Q000097:blood* / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000032:analysis; D019175:DNA Methylation / Q000187:drug effects*; D004032:Diet; D006710:Homocysteine / Q000097:blood*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D006710:Homocysteine; D004247:DNA; D008715:Methionine