title: Disruption of phospholipase Cdelta4 gene modulates the liver regeneration in cooperation with nuclear protein kinase C.
abstract: Phospholipase Cdelta4 (PLC delta4) gene has been cloned from the cDNA library of regenerating rat liver. Using PLC delta4 gene-disrupted mice (PLC delta4(-/-)), we studied a role of PLC delta4 during liver regeneration after partial hepatectomy (PH). In PLC delta4(-/-), liver regeneration occurred in an apparently normal way. However, BrdU-indices indicated that PLC delta4 gene disruption delayed the onset of DNA synthesis by 2 h. Noticeably, the BrdU-indices in PLC delta4(+/+) remained rather constant throughout S phase, 25-35%, whereas in PLC delta4(-/-), it fluctuated drastically from 25% at 34 h to 65% at late S, 42 h after PH. This fact showed that PLC delta4 gene disruption caused a higher synchronization of cell proliferation. The mRNA for PLC delta4 in PLC delta4(+/+) appeared at late G1, and the expression continued throughout S phase. PLC activity increased transiently in chromatin at the late G1 and S phases in only PLC delta4(+/+), but not in PLC delta4(-/-). The specific increases in PLC activity well correlated with the transient increases of protein kinase C (PKC) alpha in chromatin of PLC delta4(+/+). PKC epsilon also increased transiently in chromatin from PLC delta4(+/+) at late S. It is concluded that PLC delta4 regulates the liver regeneration in cooperation with nuclear PKC alpha and epsilon.
authors.affiliation: Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Akutagawa
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Fukami
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Banno
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
authors.forename: Reiji
authors.initials: R
authors.lastname: Kannagi
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yokoyama
authors.forename: Koji
authors.initials: K
authors.lastname: Oda
authors.forename: Masato
authors.initials: M
authors.lastname: Nagino
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nimura
authors.forename: Shonen
authors.initials: S
authors.lastname: Yoshida
authors.forename: Keiko
authors.initials: K
authors.lastname: Tamiya-Koizumi
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology; D004261:DNA Replication; D007527:Isoenzymes / Q000172:deficiency / Q000235:genetics*; D008115:Liver Regeneration / Q000235:genetics / Q000502:physiology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054803:Phospholipase C delta; D011493:Protein Kinase C / Q000502:physiology*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D051744:Protein Kinase C-epsilon / Q000378:metabolism; D010738:Type C Phospholipases / Q000172:deficiency / Q000235:genetics*
chemical_list: D007527:Isoenzymes; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051744:Protein Kinase C-epsilon; D010738:Type C Phospholipases; D054803:Phospholipase C delta; C518031:Plcd4 protein, mouse; C518032:Plcd4 protein, rat