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.
