Harris Robert, Turan Nahid, Kirk Christopher, Ramsden David, Waring Rosemary
School of Biosciences, The University of Birmingham, Edgbaston, Birmingham, United Kingdom.
Environ Health Perspect. 2007 Dec;115 Suppl 1(Suppl 1):51-4. doi: 10.1289/ehp.9365.
Sulfation plays an important role both in detoxification and in the control of steroid activity. Studies in rodents have shown that the conversion of dehydroepiandrosterone (DHEA) to DHEA-sulfate is involved in learning and the memory process.
The effects of a range of plasticizers and related compounds commonly encountered in the environment were evaluated kinetically against human DHEA sulfotransferase (SULT 2A1) and by reverse transcriptase-polymerase chain reaction (RT-PCR) against several enzymes involved in the synthesis of the sulfotransferase cofactor adenosine 3'-phosphate 5'-phosphosulfate (PAPS).
We found that several of the chemicals acted as competitive inhibitors of SULT 2A1 (K(i) for 4-tert-octylphenol is 2.8 microM). Additionally, after treatment of TE 671 cells with 0.005-0.5 microM 4-n-octylphenol, bis(2-ethylhexyl)phthalate, and diisodecyl phthalate, real-time RT-PCR showed dose-dependent decreases in the steady-state mRNA levels of cysteine dioxygenase type I, sulfite oxidase, and 3'-phosphate 5'-phosphosulfate synthase I.
These data suggest that environmental contaminants may exert effects on neuronal function both by direct inhibition of sulfotransferase enzymes and by interrupting the supply of PAPS, which has wider implications for endocrine disruption and xenobiotic metabolism.
硫酸化在解毒及甾体活性控制方面均发挥着重要作用。对啮齿动物的研究表明，脱氢表雄酮（DHEA）向硫酸脱氢表雄酮的转化参与学习及记忆过程。
对环境中常见的一系列增塑剂及相关化合物针对人DHEA硫酸转移酶（SULT 2A1）进行动力学评估，并通过逆转录聚合酶链反应（RT-PCR）针对参与硫酸转移酶辅因子3'-磷酸腺苷5'-磷酸硫酸酯（PAPS）合成的几种酶进行评估。
我们发现几种化学物质可作为SULT 2A1的竞争性抑制剂（4-叔辛基苯酚的K(i)为2.8 microM）。此外，用0.005 - 0.5 microM的4-正辛基苯酚、邻苯二甲酸二（2-乙基己基）酯和邻苯二甲酸二异癸酯处理TE 671细胞后，实时RT-PCR显示I型半胱氨酸双加氧酶、亚硫酸盐氧化酶和3'-磷酸5'-磷酸硫酸酯合酶I的稳态mRNA水平呈剂量依赖性下降。
这些数据表明，环境污染物可能通过直接抑制硫酸转移酶及中断PAPS的供应对神经元功能产生影响，这对内分泌干扰和外源性物质代谢具有更广泛的意义。
