Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.
Garlic extract diallyl sulfide (DAS) activates nuclear receptor CAR to induce the Sult1e1 gene in mouse liver.
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DOI：
10.1371/journal.pone.0021229
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Negishi M
中科院分区：
文献类型：
--
作者：
Sueyoshi T;Green WD;Vinal K;Woodrum TS;Moore R;Negishi M
已知大蒜提取物中的化学成分可诱导啮齿动物肝脏中的I相和II相酶。在这里，我们利用Car +/+和Car −/−小鼠证明，核异生素受体CAR调节二烯丙基硫醚（DAS）处理小鼠肝脏中雌激素磺基转移酶Sult 1 e1基因的诱导。DAS处理导致CAR在细胞核中积累，导致Car +/+雌性小鼠肝脏中的SULT 1 E1 mRNA（3，200倍）和蛋白质显著增加，但Car −/−雌性小鼠没有。DAS还诱导了其他CAR调节基因，如Cyp 2b 10、Cyp 3a 11和Gadd 45 β。与DAS处理后6小时开始的这些mRNA水平的快速增加相比，SULT 1 E1 mRNA水平在24小时后开始增加。这种对DAS的缓慢反应表明CAR需要额外的因子来激活Sult 1 e1基因，或者这种激活是间接的。尽管SULT 1 E1的显著诱导，但DAS处理的小鼠中内源性E2的血清水平没有降低或硫酸雌酮的增加，而外源性给药的E2的清除加速。
Constituent chemicals in garlic extract are known to induce phase I and phase II enzymes in rodent livers. Here we have utilized Car +/+ and Car −/− mice to demonstrate that the nuclear xenobiotic receptor CAR regulated the induction of the estrogen sulfotransferase Sult1e1 gene by diallyl sulfide (DAS) treatment in mouse liver. DAS treatment caused CAR accumulation in the nucleus, resulting in a remarkable increase of SULT1E1 mRNA (3,200 fold) and protein in the livers of Car +/+ females but not of Car −/− female mice. DAS also induced other CAR-regulated genes such as Cyp2b10, Cyp3a11 and Gadd45β. Compared with the rapid increase of these mRNA levels, which began as early as 6 hourrs after DAS treatment, the levels of SULT1E1 mRNA began increasing after 24 hours. This slow response to DAS suggested that CAR required an additional factor to activate the Sult1e1 gene or that this activation was indirect. Despite the remarkable induction of SULT1E1, there was no decrease in the serum levels of endogenous E2 or increase of estrone sulfate while the clearance of exogenously administrated E2 was accelerated in DAS treated mice.
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DOI：
10.1016/j.jsbmb.2009.02.009
发表时间：
2009-03
影响因子：
4.1
作者：
Falany, Charles N.;He, Dongning;Li, Li;Falany, Josie L.;Wilborn, Teresa W.;Kocarek, Thomas A.;Runge-Morris, Melissa
通讯作者：
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作者：
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影响因子：
4.2
作者：
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通讯作者：
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影响因子：
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通讯作者：
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