Involvement of Nuclear Phosphatidylinositol-Dependent Phospholipases C in Cell Cycle Progression during Rat Liver Regeneration

Nuclear lipid metabolism is involved in the regulation of cell proliferation. Modulation of the expression and activity of nuclear PI-phospholipase C (PI-PLC) has been reported during liver regeneration after partial hepatectomy, although it has not been determined whether different PLC isoforms play specific roles in the regulation of cell cycle progression. Here, we report evidence that the increased activity of nuclear PLCs in regenerating rat liver occurs before the peak of DNA replication and involves the enzyme activity associated to the chromatin and not that associated to the nuclear membrane. Immunocytochemical analyses indicate that PI-PLC β₁ isoform is exclusively localized at the chromatin level, PI-PLC β ₁ colocalizes with DNA replication sites much more than PI-PLC γ₁, which is also present at the nuclear envelope. These findings and the increased amount of PI-PLC γ₁ occurring after the peak of DNA replication suggest that PI-PLC β₁, and γ₁ play different roles in cell cycle progression during regenerating liver. The increased activity of PI-PLC β₁, constitutively present within the hepatocyte nucleus, should trigger DNA replication, whereas PI-PLC γ₁ should be involved in G2/M phase transition through lamin phosphorylation.