Diurnal pineal 3-O-sulphotransferase 2 expression controlled by β-adrenergic repression

Diurnal pineal 3-O-sulphotransferase 2 expression controlled by β-adrenergic repression
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DOI:
10.1074/jbc.m300828200
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发表时间:
2003-05-02
影响因子:
4.8
通讯作者:
Wang, MM
Wang, MM
中科院分区:
生物学2区
文献类型:
--
作者:
Borjigin, J;Deng, J;Wang, MM

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3-O-磺基转移酶(3OSTs)催化硫酸乙酰肝素蛋白多糖中氨基3-羟基的加成,是多种生物学功能的重要介体。我们证明了3OST2亚型在大鼠松果体中的高水平表达,特别是在白天。3OST2戏剧性的昼夜节律由颈上神经节的中枢时钟控制的活动调节,持续在持续的黑暗中,并在夜间受到光的诱导。重要的是,3OST2转录被激活松果体褪黑素形成的β-肾上腺素能激动剂阻断,并由β-肾上腺素能拮抗剂诱导,后者阻止体内褪黑素的产生。由于3OST2与松果体中控制褪黑激素节律的血清素N-乙酰转移酶的表达和调控模式相反,我们测试了3OST2在夜间被迫表达对N-乙酰基转移酶基因表达和褪黑素产生的影响,结果发现,令人惊讶的是,3OST2在夜间的表达并没有干扰褪黑激素的合成。这些数据表明,3OST2可能在松果体中发挥着一种独特的功能,可能不依赖于褪黑素的形成。
The 3-O-sulfotransferases (3OSTs) catalyze the addition of sulfate groups at the 3-OH site of glucosamine in heparan sulfate proteoglycans, which serve as critical mediators of various biological functions. We demonstrate that the 3OST2 isoform is expressed at high levels in the rat pineal specifically during the daylight hours. The dramatic diurnal rhythm of 3OST2 is regulated by central clock-controlled activities of the superior cervical ganglion, persists in constant darkness, and is inducible by light at nighttime. Importantly, 3OST2 transcription is blocked by beta-adrenergic agonists that activate the pineal melatonin formation and is induced by beta-adrenergic antagonists, which block melatonin production in vivo. Because of the inverse expression and regulation patterns of 3OST2 with serotortin N-acetyltransferase, the enzyme controlling the melatonin rhythm in the pineal, we tested the effects of forced expression of 3OST2 in the night pineals on N-acetyltransferase gene expression and melatonin production and found that, surprisingly, 3OST2 expression at night fails to interfere with melatonin synthesis. These data suggest 3OST2 may serve a unique function in the pineal that may be independent of melatonin formation.