Nitric Oxide-Mediated Cytotoxicity of Manganese in Basal Ganglia Neuronal Cells

대뇌 기저핵 신경세포에서 Nitric Oxide를 매개로 한 망간의 세포독성

  • Jung, Yong-Wook (Department of Anatomy, School of Medicine, Dongguk University) ;
  • Bae, Jae-Hoon (Department of Physiology, School of Medicine, Keimyung University) ;
  • Song, Dae-Kyu (Department of Physiology, School of Medicine, Keimyung University) ;
  • Park, Won-Kyun (Department of Physiology, School of Medicine, Keimyung University) ;
  • Ko, Bok-Hyun (Department of Anatomy, School of Medicine, Dongguk University) ;
  • Kim, Doo-Hie (Preventive Medicine, School of Medicine, Dongguk University) ;
  • Shin, Dong-Hoon (Department of Preventive Medicine, School of Medicine, Keimyung University)
  • 정용욱 (동국대학교 의과대학 해부학교실) ;
  • 배재훈 (계명대학교 의과대학 생리학교실) ;
  • 송대규 (계명대학교 의과대학 생리학교실) ;
  • 박원균 (계명대학교 의과대학 생리학교실) ;
  • 고복현 (동국대학교 의과대학 해부학교실) ;
  • 김두희 (동국대학교 의과대학 예방의학교실) ;
  • 신동훈 (계명대학교 의과대학 예방의학교실)
  • Published : 1999.12.01

Abstract

Objectives:eurotoxicity is mediated by nitric oxide(NO) in the rat primary neuronal cultures and assess the effect of $Mn^{2+}$ on the N-methyl-D aspartate(NMDA) receptors. Methods: We have used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)assay to examine the effect of cytotoxicity of $MnCl_2$ in neuronal cells , NO production was determined by measuring nirites, a stable oxidation product of NO. The neurons in the rat that contains neuronal nitric oxide synthase(nNOS) were examined by immunofluorescence and confocal microscopy. The effects of $Mn^{2+}$ on the NMDA receptors was assesed by the whole cell voltage clamp technique. Results: We showed that the NO release and NOS expression was increased with 500uM $MnCl_2$ treatment and an NOS inhibitors, $N^G-nitro-L-arginine$, prevented neurotoxicity elicited by manganese. In the electrophysiological study, $Mn^{2+}$ does not block or activate the NMDA receptors and not pass through the NMDA receptors in a neurons of basal ganglia. Conclusions: It is concluded that manganese neurotoxicity in basal ganglia was partially mediated by nitric oxide in the cell culture model.

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