The CTP: Phosphocholine cytidylyltransferase inhibitor 1-o-octadecyl-2-methyl-rac-glycero-3-phosphocholine induces apoptosis in cwsv1 hepatocytes

A. S. Vrablic, C. D. Albright, O. K. Shin, S. H. Zeisel

Research output: Contribution to journalArticle

Abstract

Choline deficiency (CD) causes apoptotic cell death in rat hepatocytes. The role of the CDP-choline pathway for phosphatidylcholine synthesis in the response of S V40 immortalized, p53 inactivated, CWSV-1 rat hepatocytes to CD in vitro was investigated. CWSV-1 hepatocytes were plated in choline sufficient (CS) (70 |aM) serum-free medium for 4 days, then treated with l-O-octadecyl-2-methylrac-glycero-3-phosphocholine (18-GPC) (40-50 nM for 6 hours), an inhibitor of CTP: phosphocholine cytidylyltransferase. 18-GPC treated cells had more DNA strand breaks (TUNEL method), exhibited classical morphological features of apoptosis, and detached from the plate at higher rates than controls. Internucleosomal DNA cleavage was assessed using agarose gel electrophoresis. Flow cytometry after bromodeoxyuridine/ propidium iodide labeling were used to measure the effects of 18-GPC on the cell cycle. CS cells progressed through the cell cycle. 18-GPC treated cells showed a decrease in the number of cells in S phase (5 percent vs 24 percent) and an increase of cells in G2 phase (12 percent vs 4 percent) compared to CS cells. These data suggest that pharmacologie inhibition of CTP: phosphocholine cytidylyltransferase induces cell cycle arrest and apoptosis via p53 independent pathway.

Original languageEnglish
JournalFASEB Journal
Volume10
Issue number3
StatePublished - 1996
Externally publishedYes

Fingerprint

Choline-Phosphate Cytidylyltransferase
Phosphorylcholine
choline
Choline
hepatocytes
Hepatocytes
apoptosis
Cells
Apoptosis
Choline Deficiency
cells
Rats
Cell Cycle
interphase
Cytidine Diphosphate Choline
cell cycle
DNA Cleavage
DNA Breaks
Flow cytometry
Agar Gel Electrophoresis

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

The CTP : Phosphocholine cytidylyltransferase inhibitor 1-o-octadecyl-2-methyl-rac-glycero-3-phosphocholine induces apoptosis in cwsv1 hepatocytes. / Vrablic, A. S.; Albright, C. D.; Shin, O. K.; Zeisel, S. H.

In: FASEB Journal, Vol. 10, No. 3, 1996.

Research output: Contribution to journalArticle

@article{b0c7eb2de3b6471088d60cf7099ac3bc,
title = "The CTP: Phosphocholine cytidylyltransferase inhibitor 1-o-octadecyl-2-methyl-rac-glycero-3-phosphocholine induces apoptosis in cwsv1 hepatocytes",
abstract = "Choline deficiency (CD) causes apoptotic cell death in rat hepatocytes. The role of the CDP-choline pathway for phosphatidylcholine synthesis in the response of S V40 immortalized, p53 inactivated, CWSV-1 rat hepatocytes to CD in vitro was investigated. CWSV-1 hepatocytes were plated in choline sufficient (CS) (70 |aM) serum-free medium for 4 days, then treated with l-O-octadecyl-2-methylrac-glycero-3-phosphocholine (18-GPC) (40-50 nM for 6 hours), an inhibitor of CTP: phosphocholine cytidylyltransferase. 18-GPC treated cells had more DNA strand breaks (TUNEL method), exhibited classical morphological features of apoptosis, and detached from the plate at higher rates than controls. Internucleosomal DNA cleavage was assessed using agarose gel electrophoresis. Flow cytometry after bromodeoxyuridine/ propidium iodide labeling were used to measure the effects of 18-GPC on the cell cycle. CS cells progressed through the cell cycle. 18-GPC treated cells showed a decrease in the number of cells in S phase (5 percent vs 24 percent) and an increase of cells in G2 phase (12 percent vs 4 percent) compared to CS cells. These data suggest that pharmacologie inhibition of CTP: phosphocholine cytidylyltransferase induces cell cycle arrest and apoptosis via p53 independent pathway.",
author = "Vrablic, {A. S.} and Albright, {C. D.} and Shin, {O. K.} and Zeisel, {S. H.}",
year = "1996",
language = "English",
volume = "10",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "3",

}

TY - JOUR

T1 - The CTP

T2 - Phosphocholine cytidylyltransferase inhibitor 1-o-octadecyl-2-methyl-rac-glycero-3-phosphocholine induces apoptosis in cwsv1 hepatocytes

AU - Vrablic, A. S.

AU - Albright, C. D.

AU - Shin, O. K.

AU - Zeisel, S. H.

PY - 1996

Y1 - 1996

N2 - Choline deficiency (CD) causes apoptotic cell death in rat hepatocytes. The role of the CDP-choline pathway for phosphatidylcholine synthesis in the response of S V40 immortalized, p53 inactivated, CWSV-1 rat hepatocytes to CD in vitro was investigated. CWSV-1 hepatocytes were plated in choline sufficient (CS) (70 |aM) serum-free medium for 4 days, then treated with l-O-octadecyl-2-methylrac-glycero-3-phosphocholine (18-GPC) (40-50 nM for 6 hours), an inhibitor of CTP: phosphocholine cytidylyltransferase. 18-GPC treated cells had more DNA strand breaks (TUNEL method), exhibited classical morphological features of apoptosis, and detached from the plate at higher rates than controls. Internucleosomal DNA cleavage was assessed using agarose gel electrophoresis. Flow cytometry after bromodeoxyuridine/ propidium iodide labeling were used to measure the effects of 18-GPC on the cell cycle. CS cells progressed through the cell cycle. 18-GPC treated cells showed a decrease in the number of cells in S phase (5 percent vs 24 percent) and an increase of cells in G2 phase (12 percent vs 4 percent) compared to CS cells. These data suggest that pharmacologie inhibition of CTP: phosphocholine cytidylyltransferase induces cell cycle arrest and apoptosis via p53 independent pathway.

AB - Choline deficiency (CD) causes apoptotic cell death in rat hepatocytes. The role of the CDP-choline pathway for phosphatidylcholine synthesis in the response of S V40 immortalized, p53 inactivated, CWSV-1 rat hepatocytes to CD in vitro was investigated. CWSV-1 hepatocytes were plated in choline sufficient (CS) (70 |aM) serum-free medium for 4 days, then treated with l-O-octadecyl-2-methylrac-glycero-3-phosphocholine (18-GPC) (40-50 nM for 6 hours), an inhibitor of CTP: phosphocholine cytidylyltransferase. 18-GPC treated cells had more DNA strand breaks (TUNEL method), exhibited classical morphological features of apoptosis, and detached from the plate at higher rates than controls. Internucleosomal DNA cleavage was assessed using agarose gel electrophoresis. Flow cytometry after bromodeoxyuridine/ propidium iodide labeling were used to measure the effects of 18-GPC on the cell cycle. CS cells progressed through the cell cycle. 18-GPC treated cells showed a decrease in the number of cells in S phase (5 percent vs 24 percent) and an increase of cells in G2 phase (12 percent vs 4 percent) compared to CS cells. These data suggest that pharmacologie inhibition of CTP: phosphocholine cytidylyltransferase induces cell cycle arrest and apoptosis via p53 independent pathway.

UR - http://www.scopus.com/inward/record.url?scp=33749108584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33749108584&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33749108584

VL - 10

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 3

ER -