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.
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.
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DOI：
10.1016/s1388-1981(99)00128-6
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发表时间：
1999-09
期刊：
影响因子：
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通讯作者：
Y. Lee;S. Kim;J. Kim;K. Young Kim;M. Kim;S. Ryu;P. Suh
中科院分区：
文献类型：
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作者：
Y. Lee;S. Kim;J. Kim;K. Young Kim;M. Kim;S. Ryu;P. Suh
紫外线C（UVC）照射诱导DNA损伤，并且经UVC照射的细胞经历细胞生长停滞以修复受损的DNA或诱导凋亡以防止肿瘤转化的风险。磷脂酶C-γ1（PLC-γ1）是生长因子诱导的信号级联反应的介导者，催化4，5-二磷酸磷脂酰水解生成第二信使甘油二酯和1，4，5-三磷酸肌醇（IP 3）。PLC-γ1在生长因子占据细胞表面受体后通过酪氨酸残基的磷酸化而被激活，并且在控制细胞增殖和分化中起重要作用。在本研究中，我们发现PLC-γ1在UVC照射后2.5分钟内被酪氨酸磷酸化。为探讨紫外线（UVC）诱导PLC-γ1酪氨酸磷酸化的作用，我们比较了UVC对PLC-γ1过表达细胞和空载体转染细胞的影响。过表达PLC-γ1可抑制紫外线诱导的亚二倍体峰和DNA片段化。北方印迹分析显示，在PLC-γ1过表达的细胞中，UV C诱导的c-fos mRNA的积累受到抑制，而c-jun的表达不受影响。另外，在PLC-γ1过表达细胞中，UV-C诱导的c-Jun N-末端激酶（JNK）的激活被显著抑制。这些结果提示，PLC-γ1可能通过抑制c-fos mRNA的积累和JNK激酶的活性，对UV-C诱导的细胞死亡进程起到保护作用。
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.