Rising zinc: a significant cause of ischemic neuronal death in the CA1 region of rat hippocampus.
There is a rising intracellular Zn2+ transient during neuronal ischemic hypoxia (oxygen-glucose deprivation and reoxygenation, OGD/R). The results of our recent works suggest that the OGD/R-induced Zn2+ transient can readily be mistaken for a Ca2+ transient. The aim of this study was to examine the respective functions of Zn2+ and Ca2+ in OGD/R-induced neuronal injury. We showed that [Zn2+]i accumulation was consistently met with the induction of OGD/R-induced cell injury. Ca2+ accumulation induced with high [K+] (to open voltage-gated calcium channels) or ionomycin (a Ca2+ ionophore) caused a moderate neuronal injury that was reduced significantly by the application of the Zn2+ chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN). In comparison, Zn2+ accumulation, induced with the Zn2+ ionophore pyrithione, resulted in significantly greater injury. The application of nimodipine and MK801 was shown to attenuate neuronal injury only from a mild (10 mins) OGD insult. Neuronal injury from more severe (30 mins) OGD was not mitigated by the ion channel antagonists, whereas treatment with the Zn2+ chelator TPEN did afford significant protection from cell injury. These results indicate Zn2+-mediated damage to be of greater consequence than Ca2+-mediated damage, and collectively support the suggestion that Zn2+ accumulation may be a more significant causal factor of OGD/R-induced neuronal injury.
Stork
Christian J
CJ
Molecular and Cellular Biology Program, Ohio University, Athens, Ohio 45701, USA.
Li
Yang V
YV
D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D005947:Glucose / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009924:Organ Culture Techniques; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000378:metabolism*
D005947:Glucose; D015032:Zinc; D010100:Oxygen; D002118:Calcium