title: Changes of nuclear PI-PLC gamma1 during rat liver regeneration.
abstract: We have previously demonstrated that rat liver nuclei contain PI-PLC beta1 and gamma1 in the inner nuclear matrix and lamina associated with specific phosphodiesterase activity (Bertagnolo et al., 1995, Cell Signall. 7, 669-678). Since compensatory hepatic growth is an informative and well characterized model for natural cell proliferation, the presence of specific PI-PLC isoforms and their activity as well as PIP2 recovery were studied at various regenerating times, ranging from 3 to 22 h after partial hepatectomy. Three PI-PLC isoforms (beta1, gamma1, delta1) were examined in control and regenerating liver cells by using specific antibodies. By means of in situ immunocytochemistry and confocal microscopy, PI-PLC beta1 was found mainly in the nucleoplasm and this pattern was not modified after hepatectomy. On the contrary, the nuclear gamma1 isoform showed a marked decrease at 3 and 16 h after hepatectomy, but a clear increase at 22 h covering with bright intensity the whole nucleus. The PI-PLC delta1 isoform, which is exclusively cytoplasmic, was not altered during rat liver regeneration. By western blotting analysis on whole cell homogenates, none of the PI-PLC isozymes under study showed proliferation-linked modification. However, analyses of isolated nuclei identified changes in the nucleus associated PI-PLC gamma1 that paralleled the in situ observation whereas the beta1 isoform was unmodified at all the times examined. Nuclear phosphodiesterase activity on PIP2 was lower at 3 and 16 h, in comparison with sham operated rats, increased at 6 h and reached the highest value after 22 h. Consistently, the recovery of PIP2, obtained in conditions that optimise PIP-kinase activity, showed a marked decrease at 3 h and an increase up to 16 h of liver regeneration, followed by a further decrease at 22 h. These data are consistent with a close relationship between cell proliferation and the nuclear inositide cycle, depending, in rat liver, predominantly on the modulation of the gamma1 isoform of PI-PLC.
authors.affiliation: Laboratory of Cell Biology, Institute of Human Anatomy, University of Ferrara, Italy.
authors.forename: L M
authors.initials: LM
authors.lastname: Neri
authors.forename: D
authors.initials: D
authors.lastname: Ricci
authors.forename: C
authors.initials: C
authors.lastname: Carini
authors.forename: M
authors.initials: M
authors.lastname: Marchisio
authors.forename: S
authors.initials: S
authors.lastname: Capitani
authors.forename: V
authors.initials: V
authors.lastname: Bertagnolo
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002455:Cell Division; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007527:Isoenzymes; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008115:Liver Regeneration / Q000502:physiology*; D018613:Microscopy, Confocal; D009687:Nuclear Proteins / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D054801:Phosphoinositide Phospholipase C; D010766:Phosphorylation; D051381:Rats; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D009687:Nuclear Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase