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 glioma cells. Incubation with 150 to 300 microM 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-pyridyl-methyl)-ethylenediamine] also induced programmed death in this cell line, indicating the existence of intracellular zinc levels below and above which apoptosis is induced. 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 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 zinc-induced 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 zinc-induced apoptosis.
Haase
H
H
Fachbereich Biologie/Chemie, Universität Bremen, Germany.
Wätjen
W
W
Beyersmann
D
D
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D003513:Cycloheximide / Q000494:pharmacology; D053938:DNA Fragmentation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007811:Lanthanum / Q000494:pharmacology*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D014176:Protein Biosynthesis; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D015032:Zinc / Q000494:pharmacology*
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D005419:Flavonoids; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D017382:Reactive Oxygen Species; D007811:Lanthanum; C041715:6-anilino-5,8-quinolinedione; D003513:Cycloheximide; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D006162:Guanylate Cyclase; D015032:Zinc; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one