Zinc Induces Apoptosis That Can Be Suppressed by Lanthanum in C6 Rat Glioma Cells

Biological Chemistry - Tập 382 Số 8 - Trang 1227-1234 - 2001
Hajo Haase1, Wim Wätjen, Detmar Beyersmann
1Fachbereich Biologie/Chemie, Universität Bremen, Germany.

Tóm tắt

AbstractZinc 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 glioma cells. Incubation with 150 to 300 M ZnCl2 caused cell death that was characterized as apoptotic by internucleosomal DNA fragmentation, formation of apoptotic bodies, nuclear fragmentation and breakdown of the mitochondrial membrane potential. On the other hand, zinc deprivation by the membrane permeable chelator TPEN [N,N,N,N,tetrakis (2-pyridylmethyl)ethylenediamine] also induced programmed death in this cell line, indicating the existence of intracellular zinc levels below and above which apoptosis is induced. Zincinduced 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 uptake 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 zincinduced breakdown of the mitochondrial membrane potential. We conclude that in C6 cells lanthanum acts in two different ways, as a promoter of net zinc uptake and as a suppressor of zincinduced apoptosis.

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Biological Chemistry

Tập 382 Số 8

1227-1234

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