Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency.
Choline-deficiency causes liver cells to die by apoptosis, and it has not been clear whether the effects of choline-deficiency are mediated by methyl-deficiency or by lack of choline moieties. SV40 immortalized CWSV-1 hepatocytes were cultivated in media that were choline-sufficient, choline-deficient, choline-deficient with methyl-donors (betaine or methionine), or choline-deficient with extra folate/vitamin B12. Choline-deficient CWSV-1 hepatocytes were not methyl-deficient as they had increased intracellular S-adenosylmethionine concentrations (132% of control; P < 0.01). Despite increased phosphatidylcholine synthesis via sequential methylation of phosphatidylethanol-amine, choline-deficient hepatocytes had significantly decreased (P < 0.01) intracellular concentrations of choline (20% of control), phosphocholine (6% of control), glycerophosphocholine (15% of control), and phosphatidylcholine (55% of control). Methyl-supplementation in choline-deficiency enhanced intracellular methyl-group availability, but did not correct choline-deficiency induced abnormalities in either choline metabolite or phospholipid content in hepatocytes. Methyl-supplemented, choline-deficient cells died by apoptosis. In a rat study, 2 weeks of a choline deficient diet supplemented with betaine did not prevent the occurrence of fatty liver and the increased DNA strand breakage induced by choline-deficiency. Though dietary supplementation with betaine restored hepatic betaine concentration and increased hepatic S-adenosylmethionine/S-adenosylhomocysteine ratio, it did not correct depleted choline (15% of control), phosphocholine (6% control), or phosphatidylcholine (48% of control) concentrations in deficient livers. These data show that decreased intracellular choline and/or choline metabolite concentrations, and not methyl deficiency, are associated with apoptotic death of hepatocytes.
Shin
O H
OH
Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill 27599-7400, USA.
Mar
M H
MH
Albright
C D
CD
Citarella
M T
MT
da Costa
K A
KA
Zeisel
S H
SH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001622:Betaine / Q000378:metabolism; D002460:Cell Line; D002796:Choline Deficiency / Q000473:pathology*; D003470:Culture Media; D005492:Folic Acid / Q000008:administration & dosage; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008297:Male; D008745:Methylation; D051381:Rats; D011916:Rats, Inbred F344; D014805:Vitamin B 12 / Q000008:administration & dosage
D003470:Culture Media; D001622:Betaine; D005492:Folic Acid; D014805:Vitamin B 12