Overexpression of phospholipase C-gamma1 suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells.
Ultraviolet-C (UVC) irradiation induces DNA damage and UVC-irradiated cells undergo cell growth arrest to repair the damaged DNA or the induction of apoptosis to prevent the risk of neoplastic transformation. Phospholipase C-gamma1 (PLC-gamma1) is a mediator of growth factor induced-signal cascade, catalyzing the hydrolysis of phosphatidyl 4,5-bisphosphate to generate second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (IP(3)). PLC-gamma1 is activated by phosphorylation of tyrosine residues upon occupation of cell surface receptors by growth factors and plays an important role in controlling cellular proliferation and differentiation. In this study, we found that PLC-gamma1 was tyrosine phosphorylated within 2.5 min after UVC irradiation. To investigate the role of UVC-induced tyrosine phosphorylation of PLC-gamma1, we compared the effect of UVC between PLC-gamma1 overexpressing cells and empty vector transfected cells. Overexpression of PLC-gamma1 inhibited UVC-induced sub-diploid peak and DNA fragmentation. Northern blot analysis revealed that UVC-induced c-fos mRNA accumulation was inhibited in PLC-gamma1 overexpressing cells, while c-jun expression was not affected. In addition, UVC-induced activation of c-Jun N-terminal kinase (JNK) was significantly suppressed in PLC-gamma1 overexpressing cells. These results suggest that PLC-gamma1 may associate with the protective function against the UVC-induced cell death progression via the inhibition of accumulation of c-fos mRNA and the inhibition of JNK kinase activity.
Lee
Y H
YH
Department of Biochemistry, College of Medicine, Yeungnam University, Taegu, South Korea.
Kim
S
S
Kim
J
J
Young Kim
K
K
Kim
M J
MJ
Ryu
S H
SH
Suh
P
P
D000818:Animals; D017209:Apoptosis; D015536:Down-Regulation; D004789:Enzyme Activation; D016762:Genes, fos; D016758:Genes, jun; D007527:Isoenzymes / Q000096:biosynthesis*; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis / Q000037:antagonists & inhibitors*; D016716:PC12 Cells / Q000201:enzymology / Q000528:radiation effects*; D051966:Phospholipase C gamma; D051381:Rats; D014158:Transcription, Genetic / Q000528:radiation effects; D014162:Transfection; D010738:Type C Phospholipases / Q000096:biosynthesis*; D014466:Ultraviolet Rays
D007527:Isoenzymes; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D010738:Type C Phospholipases; D051966:Phospholipase C gamma