N-메철-4-페날퍼러디니움 및 6-허드록시도파민으로 유도된 도파민계 신경세포 사멸 기작의 규명

• 영문명: Characterization of Dopaminergic Neuronal Cell Death Induced by either N-Methyl-4-phenylpyridinium or 6-hydroxydopamine
• 발행기관: 대한약학회
• 저자명: 오영준(Yong J Oh) 최원석(WorrSeok Choi)
• 간행물 정보: 『약학회지』제41권 제1호 (1997년), 86~93쪽, 전체 8쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 1997.01.31

영문 초록

Even though both N-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine have been widely used to establish the experimental model for dopaminergic neuronal cell death. mechanisms underlying this phenomenon have not been firmly explored. To investigate how these dopaminergic neurotoxins induce neuronal cell death, murine dopaminergic neuronal cell line, MN9D cells were treated with various concentration of either 6-hydroxydopamine or active form of MPTP, N methyl-4-phenylpyridinium (MPP+). Treatment of cells with 5-100uM 6-hydroxydopamine resulted in apoptotic cell death whereas cell death induced by 5~50uM MPP+ was not demonstrated typical apoptotic characteristics such as cell shrinkage, apoptotic body and nuclear condensation. Cell death induced by 6-hydroxydopamine was partially blocked in the presence of antioxidants including soluble form of vitamin E or desferrioxamine suggesting that generation of oxidative stress may be associated with 6-hydroxydopamine-induced cell death in MN9D cells. In contrast, MPP+-induced cell death was not blocked by treatment with any of antioxidants tested. As previously demonstrated that MPP+ caused metabolic alterations such as glucose metabolism, removal of glucose from the medium partially inhibited MPP+-induced cell death suggesting excessive cycles of glycolysis may be associated with MPP+-induced cell death. Taken together, these studies demonstrate that two types of dopaminergic neurotoxins recruit distinct neuronal cell death pathways.