PC12 세포에서 MPP+로 유발된 도파민성 독성에 대한 항산화제의 영향

Other Titles
Effects of antioxidants on MPP+-induced dopaminergic toxicity in PC12 cells
Authors
황준영
Abstract
흰쥐 교감신경세포인 PC12 세포를 대상으로 MPTP와 그 대사물인 MPP^(+)를 이용하여 도파민성 독성을 유발시키고 여러 가지 항산화제를 사용하여 2 mM MPP^(+)와 MPTP로 유발된 도파민성 세포독성에 대한 보호효과를 비교해 보고자 하였다. 0.05-1 mM NAC 단독처치나 NAC과 10^(-7) M melatonin, NAC과 100 U SOD의 병합처치는 세포생존율을 향상시키지 못하였으며, NAC과 apoptosis 억제제인 1 μM cyclosporin A를 병합하였을 때 부분적인 보호효과를 나타내었다. 0.05-3 mM OTC 단독처치나 OTC와 10 μM EGCG, OTC와 10 μM minocycline의 병합처치는 유의한 보호효과를 나타내었다. 1-10 μM EGCG 단독처치나 EGCG와 2 mM OTC, EGCG와 10 μM minocycline의 병합처치는 가장 우수한 보호효과를 나타내었다. 0.1-10 μM minocycline 단독처치나 minocycline과 10 μM EGCG의 병합처치는 유의한 보호효과를 나타내었으나 minocycline과 OTC의 병합처치는 보호효과가 없었다. D-methionine, L-NAME, estrogen, melatonin은 세포생존율을 향상시키지 못하였다. 이상의 결과에서 PC12 세포에서 MPP^(+)나 MPTP에 의해 유발된 산화스트레스에 대하여 EGCG, OTC, minocycline은 유의한 보호효과를 나타내었으며, EGCG와 OTC, EGCG와 minocycline을 병합하여 전처한 경우에 다른 항산화제에 비하여 MPP^(+)나 MPTP에 의한 산화스트레스를 효과적으로 억제할 수 있을 것으로 생각된다. MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and its metabolite MPP^(+) (1-methyl-4-phenylpyridium) are dopamine-selective neurotoxins and induce parkisonism in animal models. This study was designed to evaluate the protective effects of various antioxidants on dopaminergic toxicity induced by MPP^(+) and MPTP in PC12 cells. In 0.05 ~ 1 mM N-acetylcysteine (NAC), NAC alone, NAC + 10^(-7) M melatonin and NAC + 100 U superoxide dismutase did not show protective effects against dopaminergic toxicity with 2 mM MPP^(+). NAC + 1 μM cyclosporin A, an antiapoptocic agent, slightly increased the viability of PC12 cells against the dopaminergic toxicity induced by 2 mM MPP^(+). In 0.05 ~ 3 mM L-2-oxothiazoline-4-carboxylate (OTC), OTC alone, OTC + 10 μM (-)-epigallocatechin-3-gallate (EGCG) and OTC + 10 μM minocycline showed significant protective effects on the dopaminergic toxicity induced by 2 mM MPP^(+) or MPTP. In 1 ~ 10 μM EGCG, EGCG alone, EGCG + 2 mM OTC and EGCG + 10 μM minocycline showed most protective effects on the dopaminergic toxicity induced by 2 mM MPP^(+) or MPTP. In 0.1 ~ 10 μM minocycline, minocycline alone, minocycline + 10 μM EGCG showed significant protective effects on the dopaminergic toxicity induced by 2 mM MPP^(+) or MPTP, but not minocycline + 2 mM OTC. Other antioxidants including D-methionine, L-nitro-arginine methylester (L-NAME), estrogen and melatonin, did not show any promotion in viability of PC12 cells with the dopaminergic toxicity induced by 2 mM MPTP. In conclusion, it seems that EGCG, OTC and minocycline have inhibiting effects on oxidative stress induced by 2 mM MPP^(+) and MPTP, and combination of EGCG with OTC or EGCG with minocycline will show effective protection against MPP^(+)-induced dopaminergic toxicity in PC12 cells.
URI
http://kumel.medlib.dsmc.or.kr/handle/2015.oak/11856
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3. Thesis (학위논문) > 1. School of Medicine (의과대학) > 박사
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