【摘要】 重金属诱导的细胞凋亡是一个十分复杂的过程,不同种类的重金属以及同类重金属离子的不同价态所诱导的凋亡效应及其分子机制不尽相同。目前的研究表明,重金属与DNA形成加合物而导致DNA损伤可能是引发细胞凋亡的重要步骤:多种重金属能通过激活内质网、线粒体钙通道,使Ca²⁺释放进入细胞质而引发凋亡;重金属还能使细胞中ROS升高,在直接导致DNA损伤的同时,启动与线粒体相关的细胞凋亡信号通路。此外,ROS还能通过MAPKs增强JNK介导的FasL和Fas表达,最终使caspase-3和caspase-7激活,从而促进凋亡的发生。重金属诱导细胞凋亡还涉及一系列重要基因和蛋白质的参与,包括促进凋亡的Src家族酪氨酸激酶、bax、fas和p53等基因及相关蛋白,抑制凋亡的Sp1锌指转录因子、bcl-2和myc等基因及相关蛋白。部分重金属如镉、锌等对细胞凋亡具有诱导和拮抗双重效应,其中拮抗效应主要是通过与自由钙离子协同进行的,而诱导效应则可能是通过调节caspase-3活性而实现的。更多还原

【Abstract】 Apotosis induced by heavy metals is a complex process, in which apoptotic effects and molecularmechanisms vary with different ions or different electrovalence of same ions. Recent researches indicated thatDNA damage by adduction of DNA and ions may play an important role in apoptosis. Many heavy metal ions canactivate the calcium channels on endoplasmic reticulum and mitochondria to release calcium into cytosol wherecalcium act as a second message to trigger the apoptotic cascades and induce apoptosis. Meantime, heavy metalions can elevate the level of ROS to activate relevant apoptotic pathway in cells, as a result the expression of JNK-mediated FasL and Fas through MAPKs were upregulated, and eventually caspase-3 and caspase-7 were activatedto promote apoptosis. Expousure of cells to heavy metals also may trigger numerous expression of genes andproteins invovled in apoptosis, which include the pro-apoptotic members such as Src-family tyrosine kinase, bax,fas, p53 and the anti-apoptotic members like Spl zinc-finger tfanscription factor, bcl-2, c-myc. Some heavy metalslike cadium and zinc were of dual effects of both inducing apoptosis by activating caspase-3 and antagonizingapoptosis synergized by free calcium.更多还原