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Overexpression of phospholipase C-gamma 1 suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells

Title
Overexpression of phospholipase C-gamma 1 suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells
Authors
Lee, YHKim, SYKim, JRKim, KYKim, MJRyu, SHSuh, PGKim, JH
POSTECH Authors
Ryu, SH
Date Issued
Jan-1999
Publisher
ELSEVIER SCIENCE BV
Abstract
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-gamma 1 (PLC-gamma 1) 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 (IP3) PLC-gamma 1 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-gamma 1 was tyrosine phosphorylated within 2.5 min after UVC irradiation. To investigate the role of UVC-induced tyrosine phosphorylation of PLC-gamma 1, we compared the effect of UVC between PLC-gamma 1 overexpressing cells and empty vector transfected cells. Overexpression of PLC-gamma 1 inhibited UVC-induced sub-diploid peak and DNA fragmentation. Northern blot analysis revealed that UVC-induced c-fos mRNA accumulation was inhibited in PLC-gamma 1 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-gamma 1 overexpressing cells. These results suggest that PLC gamma 1 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. (C) 1999 Elsevier Science B.V. All rights reserved.
Keywords
ultraviolet-C; phospholipase C-gamma 1; apoptosis; c-Jun N-terminal kinase; SIGNAL-TRANSDUCTION; PROTEIN-KINASE; TYROSINE KINASE; THYMOCYTE APOPTOSIS; GENE-EXPRESSION; HA-RAS; RECEPTOR; DEATH; PHOSPHORYLATION; RADIATION
URI
http://oasis.postech.ac.kr/handle/2014.oak/20266
ISSN
1388-1981
Article Type
Article
Citation
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, vol. 1440, no. 2-3, page. 235 - 243, 1999-01
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 RYU, SUNG HO
Dept of Life Sciences
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