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        Ceramide is involved in MPP+-induced Cytotoxicity in HumanNeuroblastoma Cells

        남은주,Hye-SookLee,YoungJaeLee,Wan-SeokJoo,SunghoMaeng,임혜인,Chan-WoongPark,김용식 대한약리학회 2002 The Korean Journal of Physiology & Pharmacology Vol.6 No.6

        To understand the cytotoxic mechanism of MPP+, we examined the involvement of ceramide in MPP+ -induced cytotoxicity to human neuroblastoma SH-SY5Y cells. When SH-SY5Y cells were exposed to MPP+,MPP+ induced dose-dependent cytotoxicity accompanied by 2-fold elevation of intracellular ceramide levels in SH-SY5Y cells. Three methods were used to test the hypothesis that the elevated intracellular ceramide is related to MPP+-induced cytotoxicity: C2-ceramide was directly applied to cells, sphingomyelinase (SMase) was exogenously added, and oleoylethanolamine (OE) was used to inhibit degradation of ceramide. Furthermore, inhibition of ceramide-activated protein phosphatase (CAPP), the effector of ceramide, using okadaic acid (OA) attenuated cell death but treatment of fumonisin B1, the ceramide synthase inhibitor, did not alter the cytotoxic effect of MPP+. Based on these, we suggest that the elevation of intracellular ceramide is one of the important mediators in MPP+ -induced cell death.

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        Effects of Polycyclic Aromatic Hydrocarbons on Liver and Lung Cytochrome P450s in Mice

        JiYoungKim,SangKyuLee,ChunHwaKim,TaeWonJeon,문창규,Hye-SookLee,SunDongYoo,EungSeokLee,TaeCheonJeong 대한약학회 2003 Archives of Pharmacal Research Vol.26 No.5

        Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a,h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/ kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin- O-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs.

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        Induction of Cytochrome P450 1A and 2B by a- and b-Ionone in Sprague Dawley Rats

        HyeGwangJeong,Young-JinChun,Chul-HoYun,Chang-KiuMoon,Hye-SookLee,SangSeopHan,Eung-SeokLee,TaeCheonJeong 대한약학회 2002 Archives of Pharmacal Research Vol.25 No.3

        b-Ionone has been reported to induce the cytochrome P450 (P450) 2B1 in rats. In this study, the effects of b-ionone and an isomer, a-ionone, on liver P450 1A and 2B expression in Sprague Dawley rats were investigated. Subcutaneous administration of a- and b-ionone 72 and 48 hr prior to sacrificing the animals induced the liver microsomal P450 1A and 2B proteins. P450 2B1 induction was associated with the accumulation of its corresponding mRNA. Induction by b-ionone was much higher than that by a-ionone in both the mRNA and protein levels. When the route of administration was compared, P450 2B was induced more strongly after oral administration compared to that after subcutaneous injection. A single oral dose of 100, 300 and 600 mg/kg of a- and b-ionone for 24 h induced P450 2B1-selective pentoxyresorufin Odepentylase activity comparably in a dose-dependent manner. In addition, a- and b-ionone induced the P450 1A and 2B proteins. These results suggest that a- and b-ionone might be potent P450 2B1 inducers in rats, and that both ionones may be useful for examining the role of metabolic activation in chemical-induced toxicity where metabolic activation is required.

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