Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency

Ok Ho Shin, Mei Heng Mar, Craig D. Albright, Maria T. Citarella, Kerry Ann Da Costa, Steven H. Zeisel

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

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 phosphatidylethanolamine, 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.

Original languageEnglish (US)
Pages (from-to)196-208
Number of pages13
JournalJournal of Cellular Biochemistry
Volume64
Issue number2
DOIs
StatePublished - Feb 1997
Externally publishedYes

Fingerprint

Choline Deficiency
Choline
Rats
Hepatocytes
Betaine
Phosphatidylcholines
S-Adenosylmethionine
Phosphorylcholine
Liver
Metabolites
S-Adenosylhomocysteine
Apoptosis

Keywords

  • apoptosis
  • betaine
  • choline
  • methionine
  • phosphatidylcholine

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency. / Shin, Ok Ho; Mar, Mei Heng; Albright, Craig D.; Citarella, Maria T.; Da Costa, Kerry Ann; Zeisel, Steven H.

In: Journal of Cellular Biochemistry, Vol. 64, No. 2, 02.1997, p. 196-208.

Research output: Contribution to journalArticle

Shin, Ok Ho ; Mar, Mei Heng ; Albright, Craig D. ; Citarella, Maria T. ; Da Costa, Kerry Ann ; Zeisel, Steven H. / Methyl-group donors cannot prevent apoptotic death of rat hepatocytes induced by choline-deficiency. In: Journal of Cellular Biochemistry. 1997 ; Vol. 64, No. 2. pp. 196-208.
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