Impaired phosphatidylcholine biosynthesis does not attenuate liver regeneration after 70% partial hepatectomy in hepatic CTP:phosphocholine cytidylyltransferase-α deficient mice.
Phosphatidylcholine (PC) is the major component of mammalian membranes, and the induction of PC biosynthesis has been shown to be an essential step in cell proliferation in various cell lines. Cytidine triphosphate (CTP):phosphocholine cytidylyltransferase α (CTα) regulates the primary pathway of PC biosynthesis in the liver. The targeted disruption of CTα in murine liver (LCTα(-/-) mice) decreases hepatic PC mass and the number of cells in the liver, suggesting CTα as an important factor for hepatocyte proliferation. To elucidate the role of CTα in hepatic cell division in vivo, we monitored liver regeneration after 70% partial hepatectomy in LCTα(-/-) and loxP flanked (floxed) LCTα  (control) mice. To our surprise, liver re-growth, DNA synthesis, and PC mass after surgery were not impaired in LCTα(-/-) mice, despite reduced total PC synthesis. Furthermore, PC synthesis in the control mice was not induced after 70% partial hepatectomy. We conclude that CTα is not essential for proliferation of hepatocytes in vivo, and that basal hepatic PC biosynthesis is sufficient to sustain regeneration after 70% partial hepatectomy.
Group on the Molecular and Cell Biology of Lipids, University of Alberta, Edmonton, AB T6G 2S2, Canada.
Ji
J
Ling
Lin Fu
LF
Zhu
Dennis E
DE
Vance
René L
RL
Jacobs
D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D019916:Choline-Phosphate Cytidylyltransferase / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D059305:Diet, High-Fat / Q000009:adverse effects; D006498:Hepatectomy / Q000009:adverse effects; D006529:Hepatomegaly / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D050356:Lipid Metabolism; D008099:Liver / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008115:Liver Regeneration; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010713:Phosphatidylcholines / Q000096:biosynthesis*; D010714:Phosphatidylethanolamines / Q000096:biosynthesis; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D014280:Triglycerides / Q000096:biosynthesis
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D018809:Proliferating Cell Nuclear Antigen; D014280:Triglycerides; C483858:phosphatidylethanolamine; D004247:DNA; D019916:Choline-Phosphate Cytidylyltransferase; C500611:Pcyt1a protein, mouse