Acidosis and 5-(N-ethyl-N-isopropyl)amiloride (EIPA) attenuate zinc/kainate toxicity in cultured cerebellar granule neurons

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• 作者：E. V. Stelmashook ; S. V. Novikova ; G. A. Amelkina ; E. G. Ivashkin…
• 关键词：zinc ; calcium ; kainate ; cerebellar granule neurons ; acidosis ; EIPA
• 刊名：Biochemistry (Moscow)
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：80
• 期：8
• 页码：1065-1072
• 全文大小：1,381 KB
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• 作者单位：E. V. Stelmashook (1)
  S. V. Novikova (1)
  G. A. Amelkina (2)
  E. G. Ivashkin (1)
  E. E. Genrikhs (1)
  L. G. Khaspekov (1)
  N. K. Isaev (1) (2)
  
  1. Research Center of Neurology, Russian Academy of Medical Sciences, 125367, Moscow, Russia
  2. Lomonosov Moscow State University, Belozersky Institute of Physico-Chemical Biology, 119991, Moscow, Russia
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Life Sciences
  Biochemistry
  Bioorganic Chemistry
  Microbiology
  Biomedicine
  Russian Library of Science
  
• 出版者：MAIK Nauka/Interperiodica distributed exclusively by Springer Science+Business Media LLC.
• ISSN：1608-3040

文摘

Cultured cerebellar granule neurons (CGNs) are resistant to the toxic effect of ZnCl2 (0.005 mM, 3 h) and slightly sensitive to the effect of kainate (0.1 mM, 3 h). Simultaneous treatment of CGNs with kainate and ZnCl2 caused intensive neuronal death, which was attenuated by external acidosis (pH 6.5) or 5-(N-ethyl-N-isopropyl)amiloride (EIPA, Na+/H+ exchange blocker, 0.03 mM). Intracellular zinc and calcium ion concentrations ([Zn2+]i and [Ca2+]i) were increased under the toxic action of kainate + ZnCl2, this effect being significantly decreased on external acidosis and increased in case of EIPA addition. Neuronal Zn2+ imaging demonstrated that EIPA increases the cytosolic concentration of free Zn2+ on incubation in Zn2+-containing solution. These data imply that acidosis reduces ZnCl2/kainate toxic effects by decreasing Zn2+ entry into neurons, and EIPA prevents zinc stores from being overloaded with zinc.