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논문 기본 정보

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학술저널
저자정보
이지형 (제주대학교) Khulan Amarsanaa (제주대학교) 우진지 (제주대학교) 전상찬 (제주대학교) 추연지 (제주대학교) 정성철 (제주대학교) 박덕배 (제주대학교) 김세재 (제주대학교) 한상헌 (제주대학교) 김현욱 (고려대학교) 류임주 (고려대학교) 은수용 (제주대학교)
저널정보
대한약리학회 The Korean Journal of Physiology & Pharmacology The Korean Journal of Physiology & Pharmacology 제22권 제3호
발행연도
2018.5
수록면
311 - 319 (9page)
DOI
https://doi.org/10.4196/kjpp.2018.22.3.311

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Mitochondrial calcium overload is a crucial event in determining the fate of neuronal cell survival and death, implicated in pathogenesis of neurodegenerative diseases. One of the driving forces of calcium influx into mitochondria is mitochondria membrane potential (ΔΨm). Therefore, pharmacological manipulation of ΔΨm can be a promising strategy to prevent neuronal cell death against brain insults. Based on these issues, we investigated here whether nobiletin, a Citrus polymethoxylated flavone, prevents neurotoxic neuronal calcium overload and cell death via regulating basal ΔΨm against neuronal insult in primary cortical neurons and pure brain mitochondria isolated from rat cortices. Results demonstrated that nobiletin treatment significantly increased cell viability against glutamate toxicity (100 μM, 20 min) in primary cortical neurons. Real-time imaging-based fluorometry data reveal that nobiletin evokes partial mitochondrial depolarization in these neurons. Nobiletin markedly attenuated mitochondrial calcium overload and reactive oxygen species (ROS) generation in glutamate (100 μM)-stimulated cortical neurons and isolated pure mitochondria exposed to high concentration of Ca2+ (5 μM). Nobiletininduced partial mitochondrial depolarization in intact neurons was confirmed in isolated brain mitochondria using a fluorescence microplate reader. Nobiletin effects on basal ΔΨm were completely abolished in K+-free medium on pure isolated mitochondria. Taken together, results demonstrate that K+ influx into mitochondria is critically involved in partial mitochondrial depolarization?related neuroprotective effect of nobiletin. Nobiletin-induced mitochondrial K+ influx is probably mediated, at least in part, by activation of mitochondrial K+ channels. However, further detailed studies should be conducted to determine exact molecular targets of nobiletin in mitochondria.

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