钙和内质网通路参与对氧磷诱导的el4细胞凋亡生物学动物学专业论文.docxVIP

兰州大学博I：学位论文：钙确l内质I叫通路参与对氧磷诱导的EL4细胞凋上从而抑制钙离子从内质网的释放。 兰州大学博I：学位论文：钙确l内质I叫通路参与对氧磷诱导的EL4细胞凋上 从而抑制钙离子从内质网的释放。 本研究的实验结果表明，对氧磷在浓度范用1．J0 nM时处理EL4细胞16 h后，能以浓 度依赖的模式诱导细胞凋亡率显著上升。1．10 nM对氧磷还以浓度依赖的模式诱导EL4细胞 内钙信号在凋亡的甲．期(O-2 h)增强。分别用EGTA、且I：素和普鲁卡冈对EL4细胞进行预处理 可以部分地抑制对氧磷诱导的EL4细胞内钙信号增强和细胞凋亡。此外，对氧磷还可以以 浓度依赖的模式上调caspase-12的表达量。分别用EGTA、骨I：素和普鲁卡冈埘EL4细胞进行 预处理能显著抑制对氧磷诱导的caspase一12表达量上升现象。 这些实验结果显示，对氧磷可以在EL4细胞巾诱导钙信号的上升，此种上升发牛在对 氧磷诱导的EL4细胞凋产过程的．早期(0-2 h)。钙信号的上升来源于细胞外钙离子的内流和 内质网存储的钙离子的释放，内质网存储的钙离子丰要是通过IP3受体相关的钙通道和兰尼 定受体相关的钙通道释放。本研究首次证明钙信号是对氧磷诱导的EIA细胞凋产过程中重 要的上游信号，内质网通路也参与了该凋亡过程的信号传递。 关键词xC-氧e,；EL4细胞：凋亡二；钙信号；内质网；IP3受体相关的钙通道： 兰尼定受体相关的钙通道；Caspase-12激光扫描共聚焦显微技术 -2． 兰州人学博士学化论文：钙和内质嘲通路参与对氧磷诱导的EL4细胞硐LAbstract 兰州人学博士学化论文：钙和内质嘲通路参与对氧磷诱导的EL4细胞硐L Abstract Organophosphorus compounds(OPCs)are frequently utilized in agriculture，industry and medicine all the world．Because of their wide uses，OPCs also widespread environmental pollutants and potent toxicants to many kinds of organisms，including human beings．Therefore， until the present time，toxic effects and toxicological mechanisms of OPCs have been attended to and been studied in vitro in vivo by many researchers．In recent years，more and more studies have indicated that induction of apoptosis is new toxic effect of OPCs，in vitro in vivo，and that apoptotic cell death may play important role in OPC-mediated impairing effects．It is necessary to elucidate molecular mechanisms involved in OPC—induced apoptosis，and some researchers have investigated signaling pathways in apoptosis induced by OPCs． According to results obmined now,intracellular calcium signaling has been strongly implicated in induction of apoptosis and regulation of the apoptotic signaling pathways and the endoplasmic reticulum(ER)一associated pathway is of the three major apoptotic pathways which have been found to date．Until the present time，no has investigated whether intracellular calcium signals were involved in OPC-induced apoptosis at the early stage of apoptotic process，and whether the ER-