Zinc induces apoptosis that can be suppressed by lanthanum in C6 rat glioma cells

Zinc ions have both essential and toxic effects on mammalian cells. Here we report the ability of zinc to act as an inducer of apoptosis in C6 rat gli oma cells. Incubation with 150 to 300 pm ZnCl2 caused cell death that was c haracterized as apoptotic by internucleosomal DNA fragmentation, formation of apoptotic bodies, nuclear fragmentation and breakdown of the mitochondri al membrane potential. On the other hand, zinc deprivation by the membrane permeable chelator TPEN [N,N,N ' ,N ',-tetrakis (2-pyridyl-methyl)ethylened iamine] also induced programmed death in this cell line, indicating the exi stence of intracellular zinc levels below and above which apoptosis is indu ced. Zinc-induced apoptosis in C6 cells was independent of major signaling pathways (protein kinase C, mitogen activated protein kinase and guanylate cyclase) and protein synthesis, but was increased by facilitating zinc upta ke with the ionophore pyrithione. Lanthanum(III) chloride was also able to increase the net zinc uptake, but nevertheless apoptotic features and zinc toxicity were reduced. Remarkably, lanthanum suppressed the zinc-induced br eakdown of the mitochondrial membrane potential. We conclude that in C6 cel ls lanthanum acts in two different ways, as a promoter of net zinc uptake a nd as a suppressor of zinc-induced apoptosis.