The Molecular Mechanisms of Apoptosis Induced by Heavy Metals

Abstract: Apotosis induced by heavy metals is a complex process， in which apoptotic effects and molecular mechanisms vary with different ions or different electrovalence of same ions. Recent researches indicated that DNA damage by adduction of DNA and ions may play an important role in apoptosis. Many heavy metal ions can activate the calcium channels on endoplasmic reticulum and mitochondria to release calcium into cytosol where calcium act as a second message to trigger the apoptotic cascades and induce apoptosis. Meantime， heavy metal ions 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 activated to promote apoptosis. Expousure of cells to heavy metals also may trigger numerous expression of genes and proteins invovled in apoptosis， which include the pro-apoptotic members such as Src-family tyrosine kinase， bax， fas， p53 and the anti-apoptotic members like Sp1 zinc-finger transcription factor， bcl-2， c-myc. Some heavy metals like cadium and zinc were of dual effects of both inducing apoptosis by activating caspase-3 and antagonizing apoptosis synergized by free calcium.

CSTR: 32200.14.cjcb.2004.03.0006