Photodynamic therapy mediated induction of early response genes.
Photodynamic therapy mediated induction of early response genes.
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发表时间：
1994-03
期刊：
影响因子：
11.2
通讯作者：
M. Luna;S. Wong;C. Gomer
中科院分区：
文献类型：
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作者：
M. Luna;S. Wong;C. Gomer
光动力疗法（PDT）产生活性氧物质，其引发该肿瘤治疗的细胞毒性事件。我们证明，PDT介导的氧化应激诱导的早期反应基因c-fos，c-jun，c-myc和c-myc-1在小鼠辐射诱导的纤维肉瘤细胞的瞬时增加。在黑暗中用卟啉类光敏剂孵育指数生长的细胞也诱导早期反应基因的mRNA水平增加。然而，黄嘌呤光敏剂，虎红，产生增加c-fos mRNA水平，只有在光处理。核径流实验证实，c-fos mRNA的诱导部分地在转录水平上受到控制。同样，氯霉素乙酰转移酶报告构建含有主要的c-fos转录反应元件诱导卟啉和PDT。PDT介导的c-fos激活相关的信号转导途径进行了研究，通过处理细胞与蛋白激酶抑制剂。星形孢菌素和1-（5-异喹啉磺酰基）-2-甲基哌嗪抑制PDT介导的c-fos激活，而N-（2-胍基乙基）-5-异喹啉磺酰胺则无此作用。抑制磷脂酶活性的奎纳克林可阻断PDT诱导的c-fos mRNA表达。这些结果表明，光敏剂介导的氧化应激通过蛋白激酶介导的信号转导途径激活早期反应基因。
Photodynamic therapy (PDT) generates reactive oxygen species which initiate the cytotoxic events of this tumor treatment. We demonstrate that PDT mediated oxidative stress induced a transient increase in the early response genes c-fos, c-jun, c-myc, and egr-1 in murine radiation-induced fibrosarcoma cells. Incubation of exponentially growing cells with porphyrin based photosensitizers in the dark also induced an increase in mRNA levels of early response genes. However, the xanthine photosensitizer, rose bengal, produced increased c-fos mRNA levels only following light treatment. Nuclear runoff experiments confirmed that the induction of c-fos mRNA is controlled in part at the level of transcription. Likewise, a chloramphenicol acetyltransferase reporter construct containing the major c-fos transcriptional response elements was inducible by porphyrin and PDT. Signal transduction pathways associated with PDT mediated c-fos activation were examined by treating cells with protein kinase inhibitors. Staurosporine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine inhibited PDT mediated c-fos activation while N-(2-guanidinoethyl)-5-isoquinoline-sulfonamide had no effect. In addition, quinacrine, which can inhibit phospholipase activity, blocked PDT induced c-fos mRNA expression. These results suggest that photosensitizer mediated oxidative stress acts through protein kinase-mediated signal transduction pathway(s) to activate early response genes.