Physiological role for zinc in prevention of apoptosis (gene-directed death).
Chronic lymphatic leukaemia (CLL) cells were used to study regulation of apoptosis by Zn2+. Apoptosis occurred spontaneously in a proportion of the cells during culture for 18h and in most of the cells exposed to colchicine. Spontaneous and colchicine-induced DNA fragmentation and cell death were completely inhibited in the presence of physiological concentrations of Zn2+ with Zn2+ ionophores. Chelation of intracellular Zn2+ induced DNA fragmentation and morphological changes of apoptosis in most CLL cells within 5hr, but not in a population of CLL cells which were resistant to other apoptotic stimuli. Phorbol esters inhibited apoptosis induced by colchicine and other stimuli, but had no effect on apoptosis induced by chelation of intracellular Zn2+. We propose that an intracellular pool of chelatable Zn2+ blocks apoptosis and that this pool is increased by uptake from the medium.
Zalewski
P D
PD
Department of Medicine, University of Adelaide, Queen Elizabeth Hospital, Woodville, South Australia.
Forbes
I J
IJ
Giannakis
C
C
D002413:Cations, Divalent / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D002850:Chromatography, Gel; D003078:Colchicine / Q000494:pharmacology; D004247:DNA / Q000187:drug effects*; D005029:Ethylenediamines / Q000494:pharmacology; D015451:Leukemia, Lymphocytic, Chronic, B-Cell; D008858:Microscopy, Phase-Contrast; D010618:Phenanthrolines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D013431:Sulfates / Q000494:pharmacology; D013871:Thiones; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology / Q000502:physiology*; D019287:Zinc Sulfate
D002413:Cations, Divalent; D002614:Chelating Agents; D005029:Ethylenediamines; D010618:Phenanthrolines; D010703:Phorbol Esters; D011725:Pyridines; D013431:Sulfates; D013871:Thiones; C008704:pyrithione; D019287:Zinc Sulfate; D004247:DNA; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine; D003078:Colchicine; C025205:1,10-phenanthroline