Overexpression of phospholipase C-γ1 suppresses UVC-induced apoptosis through inhibition of c-fos accumulation and c-Jun N-terminal kinase activation in PC12 cells

Young Han Lee, Seong Yong Kim, Jae Ryong Kim, Ki Young Kim, Myung Jong Kim, Sung Ho Ryu, Pann Ghill Suh, Jung Hye Kim

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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-γ1 (PLC-γ1) 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-γ1 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-γ1 was tyrosine phosphorylated within 2.5 min after UVC irradiation. To investigate the role of UVC-induced tyrosine phosphorylation of PLC-γ1, we compared the effect of UVC between PLC-γ1 overexpressing cells and empty vector transfected cells. Overexpression of PLC-γ1 inhibited UVC-induced sub-diploid peak and DNA fragmentation. Northern blot analysis revealed that UVC-induced c-fos mRNA accumulation was inhibited in PLC-γ1 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-γ1 overexpressing cells. These results suggest that PLC-γ1 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. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)235-243
Number of pages9
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1440
Issue number2-3
DOIs
StatePublished - Sep 22 1999

Keywords

  • Apoptosis
  • Phospholipase C-γ1
  • Ultraviolet-C
  • c-Jun N-terminal kinase

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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