Blockade of calcium entry accelerates arsenite-mediated apoptosis in rat cerebellar granule cells.
Arsenical exposure can cause defects in the central nervous system, yet the underlying cellular and molecular mechanisms are largely unknown. We have recently demonstrated that sodium arsenite induces apoptosis of cultured cortical and cerebellar neurons, suggesting that arsenite-induced neuronal apoptosis may contribute to at least some of its neurotoxic effects. Here we investigated the effect of Ca2+ on arsenite-mediated cerebellar granule neuron death. Sodium arsenite induced apoptosis in cerebellar neurons which were maintained in the presence of serum and depolarizing concentrations of potassium chloride (25 mM KCI). Under these conditions, inhibition of calcium entry by N-methyl-D-aspartate (NMDA) receptor blocker DL-aminophosphonovalerate (APV) or calcium channel antagonist nifedipine increased arsenite-induced apoptosis, while APV or nifedipine alone had little effect on cell viability. In cortical neurons or cerebellar neurons maintained at low potassium (5 mM), arsenite also induced apoptosis. However, the addition of APV or nifedipine did not alter levels of arsenite-induced apoptosis. These data suggest that arsenite-mediated apoptosis is regulated by intracellular calcium levels.
Namgung
Uk
U
Department of Environmental Health and Pharmacology, University of Washington, Seattle, WA 98195-7234, USA.
Kim
Dong-Hee
DH
Lim
Seok-Rhin
SR
Xia
Zhengui
Z
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018053:Arsenites / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009543:Nifedipine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D051381:Rats; D014665:Vasodilator Agents / Q000494:pharmacology
D018053:Arsenites; D014665:Vasodilator Agents; D009543:Nifedipine; C015001:arsenite; D011188:Potassium; D002118:Calcium