論文

査読有り
2013年4月

Protective Effects of Apomorphine against Zinc-Induced Neurotoxicity in Cultured Cortical Neurons

BIOLOGICAL & PHARMACEUTICAL BULLETIN
  • Hirokazu Hara
  • ,
  • Asuka Maeda
  • ,
  • Tetsuro Kamiya
  • ,
  • Tetsuo Adachi

36
4
開始ページ
585
終了ページ
591
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1248/bpb.b12-00962
出版者・発行元
PHARMACEUTICAL SOC JAPAN

There is evidence that excessive zinc (Zn2+) release from presynaptic terminals following brain injuries such as ischemia and severe epileptic seizures induces neuronal cell death. Apomorphine (Apo), a dopamine receptor agonist, has been shown to have pleiotropic biological functions. In this study, we investigated whether Apo protects cultured cortical neurons from neurotoxicity provoked by excessive Zn2+ exposure. Pretreatment with Apo dose- and time-dependently ameliorated Zn2+ neurotoxicity. In addition, pretreatment with Apo prevented intracellular nicotinamide adenine dinucleotide (NAD(+)) and ATP depletion caused by Zn2+ exposure. Dopamine receptor antagonists did not influence Apo protection against Zn2+ neurotoxicity. Apo is shown to be autoxidized to produce oxidized products such as reactive oxygen species and quinones. N-Acetylcysteine, a thiol compound, partially reduced Apo protection. Entry of Zn2+ into neurons is thought to be a critical step of Zn2+ neurotoxicity. Interestingly, we found that pretreatment with Apo decreased elevation of intracellular Zn2+ levels after Zn2+ exposure and induced mRNA expression of the zinc transporter ZnT1, which transports intracellular Zn2+ out of cells, and metallothionein. Taken together, these results suggest that the protective effects of Apo are regulated, at least in part, by its oxidized products, and preventing intracellular accumulation of Zn2+ contributes to Apo protection against Zn2+ neurotoxicity.

Web of Science ® 被引用回数 : 7

リンク情報
DOI
https://doi.org/10.1248/bpb.b12-00962
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/23546293
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000316832500012&DestApp=WOS_CPL