• Biomolecules & Therapeutics
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• 제11권2호
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• pp.112-118
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• 2003

1-Methylated $\beta$-carbolines (harmaline and harmalol) and antioxidants (N-acetylcysteine and ascorbate) reduced the loss of cell viability in differentiated PC 12 cells treated with 5 mM glutamate. $\beta$-Carbolines prevented the glutamate-induced decrease in mitochondrial membrane potential, cytochrome c release and caspase-3 activation in PC 12 cells. $\beta$-Carbolines reduced the formation of reactive oxygen species and depletion of glutathione due to glutamate in PC12 cells. $\beta$-Carbolines revealed a scavenging action on hydrogen peroxide and reduced the iron and EDTA-mediated degradation of 2-deoxy-D-ribose. The results suggest that I-methylated $\beta$-carbolines attenuate the cytotoxic effect of glutamate on PC12 cells by reducing the alteration of mitochondrial membrane permeability that seems to be mediated by oxidative stress.

• Biomolecules & Therapeutics
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• 제12권1호
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• pp.9-18
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• 2004

Opening of the mitochondrial permeability transition pore has been recognized to be involved in cell death. The present study investigated the effect of ${\beta}$-carbolines (harmaline and harmalol) and deprenyl on the dopamine-induced change in the mitochondrial membrane permeability and cell death in differentiated PC12 cells. Cell death due to 250 4{\mu}$M dopamine was inhibited by caspase inhibitors (z-IETD.fmk, z-LEHD.fmk and z-DQMD.fmk) and antioxidants (N-acetylcysteine, ascorbate, superoxide dismutase, catalase and carboxy-PTIO). ${\beta}$-Carbolines prevented the dopamine-induced cell death in PCl2 cells, while deprenyl did not inhibit cell death. ${\beta}$-Carbolines decreased the condensation and fragmentation of nuclei caused by dopamine in PC12 cells. ${\beta}$-Carbolines inhibited the decrease in mitochondrial transmembrane potential, cytochrome c release, formation of reactive oxygen species and depletion of GSH caused by dopamine in PC12 cells, whereas deprenyl did not decrease dopamine-induced mitochondrial damage. ${\beta}$-Carbolines, deprenyl and antioxidants depressed the formation of nitric oxide and melanin in dopamine-treated PC12 cells. The results suggest that cell death due to dopamine PC12 cells is mediated by caspase-8, -9 and -3. Unlike deprenyl, ${\beta}$-carbolines may attenuate the dopamineinduced cell death in PC12 cells by suppressing change in the mitochondrial membrane permeability through inhibition of the toxic action of reactive oxygen and nitrogen species.

• Biomolecules & Therapeutics
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• 제10권3호
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• pp.152-158
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• 2002

The present study elucidated the effect of $\beta$-carbolines (harmaline and harmalol) on brain mitochondlial dysfunction caused by the tyrosinase-induced oxidation of dopamine. Harmaline, harmalol and antioxidant enzymes (SOD and catalase) attenuated the dopamine-induced alteration of membrane potential, cytochrome c release and thiol oxidation in mitochondria. In contrast, antioxidant enzymes failed to reverse mitochondrial dysfunction induced by dopmnine plus tyrosinase. $\beta$-Carbolines decreased the damaging effect of dopamine plus tyrosinase against mitochondria, except no effect of harmalol on thiol oxidation. Antioxidant enzymes decreased the melanin formation from dopamine in the reaction mixture containing mitochondria but did not reduce the formation of dopamine quinone caused by tyrosinase. Both harmalol and harmaline inhibited the formation of reactive quinone and melanin. Harmalol being more effective for quinone formation and vise versa. The results indicate that compared to MAO-induced dopamine oxidation, the toxic effect of dopamine in the presence of tyrosinase against mitochondria may be accomplished by the dopamine quinone and toxic substances other than reactive oxygen species. $\beta$-Carbolines may decrease the dopamine plus tyrosinase-induced brain mitochondrial dysfunction by inhibition of the formation of reactive quinone and the change in membrane permeability.

• 대한약학회:학술대회논문집
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• 대한약학회 2003년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2-2
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• pp.85.2-85.2
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• 2003

In vivo aromatic ${\beta}$-carbolines, such as harman and norharman, may easily be formed by cyclization of indoleamines with e.g. aldehydes. Because of the structural similarity to MPTP, ${\beta}$-carbolines have been proposed as endogenous toxins. In this study, we have investigated the effects of harman and norharman on dopamine biosynthesis and L-DOPA-induced cytotoxicity in PC12 cells. Treatment of PC12 cells with harman and norharman showed 48.8% and 49.5% inhibition of dopamine content at a concentration of 20 ${\mu}$M and 100 ${\mu}$M for 48h. (omitted)

• Bulletin of the Korean Chemical Society
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• 제7권6호
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• pp.478-479
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• 1986

• Bulletin of the Korean Chemical Society
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• 제7권3호
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• pp.253-254
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• 1986

• 한국응용과학기술학회지
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• 제36권2호
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• pp.676-684
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• 2019

자연에서도 생합성이 되는 테트라하이드로-${\beta}$-카볼린 화합물은 Pictet-Spengler반응을 통해서 화학적으로도 합성된다. 본 연구에서는 ${\beta}$-카볼린 화합물을 쉽고 효과적으로 합성할 수 있는 친환경 합성법을 개발하여 유기용매가 아닌 물을 사용하여 합성하였다. 이 화합물은 투명한 결정형의 생성물로 얻어지므로 복잡한 분리과정이 필요하지 않다. 합성된 화합물은 NMR 및 UPLC/MS를 이용하여 구조를 확인하였다. 화합물 1의 이론적 분자량($C_{17}H_{17}N_2$ 249.1392), 화합물 2 ($C_{17}H_{23}N_2$ 255.1861), 화합물 3($C_{19}H_{21}N_2O_3$ 325.1552), 화합물 4($C_{19}H_{19}N_2O$ 279.1497)과 측정된 화합물들의 질량과 비교하였다. 그 결과 측정된 화합물 1의 분자량 ($[M+H]^+m/z$ detected 249.1315), 2 (detected 255.1789), 3 (detected 325.1460) 그리고 4 (detected 279.1364)와 거의 일치함으로써 생성된 화합물이 1~4의 구조를 가지고 있음을 확인하였다. 합성된 화합물들을 그람 음성균인 E. coli $DH5{\alpha}$를 대상으로 항균효과를 조사한 결과 강한 저해효과를 확인할 수 있었다.

• 대한약리학회지
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• 제31권3호
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• pp.345-353
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• 1995

Harmaline을 포함한 ${\beta}-Carboline$ 알카로이드들은 마이크로조움의 효소성 또는 비효소성 지질 과산화를 억제한다고 제시되고 있으나, 이들의 항산화 작용기전은 분명하지 않다. 본 연구에서는 $Fe^{2+}$와 $H_2O_2$에 의한 hyaluronic acid, 지질과 콜라젠의 산화성 손상에 있어 harmaline과 harmalol의 항산화 능력을 관찰하였다. 또한 반응성 산소대사물에 대한 이들의 제거작용을 조사하였다. Harmaline, harmalol, superoxide dismutase, catalase와 DMSO는 $Fe^{2+}$와 $H_2O_2$에 의한 hyaluronic acid의 변성과 $Fe^{2+}$에 의한 지질 과산화를 억제하였다. 이들 반응에서 DABCO는 hyaluronic acid의 변성을 억제하였으나 지질 과산화에 영향을 나타내지 않았다. ${\beta}-Carboline$은 $Fe^{2+}$, $H_2O_2$와 ascorbic acid에 의한 cartilage collagen의 변성을 억제하였다. Superoxide dismutase에 의하여 억제되는 $Fe^{2+}$의 자가산화에 따른 ferricytochrome c의 환원은 harmaline과 harmalol의 영향을 받지 않았다. 또한 이들은 $H_2O_2$에 대하여 분해작용을 나타내지 않았다. $Fe^{2+}$와 $H_2O_2$의 존재하에서 OH 생성은 harmaline, harmalol과 DMSO에 의하여 억제되었다. Harmaline과 harmalol은 반응성 산소대사물인 OH 과 아마도 철이온-산소 복합체에 대한 제거작용으로써 $Fe^{2+}$와 $H_2O_2$에 의한 hyaluronic acid, 지질과 콜라젠의 산화성 손상을 억제하고, 항산화 능력을 나타낼 것으로 추정된다.