Expression and Localization of Cytosolic Sulfotransferase (SULT) 1A1 and SULT1A3 in Normal Human Brain
Expression and Localization of Cytosolic Sulfotransferase (SULT) 1A1 and SULT1A3 in Normal Human Brain
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DOI：
10.1124/dmd.108.025767
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发表时间：
2009-04-01
影响因子：
3.9
通讯作者：
Falany, Charles N.
中科院分区：
文献类型：
--
作者：
Salman, Emily D.;Kadlubar, Susan A.;Falany, Charles N.
胞质磺基转移酶 (SULT) 是 II 期药物代谢酶家族，可催化磺酸基从 3'-磷酸腺苷 5'-磷酸硫酸盐转移到内源性和异生化合物。已在人脑中检测到多种 SULT 同工型信息；然而，蛋白质表达模式尚未得到表征。使用从正常成人大脑的颞上回、海马、小脑、枕极、额极和颞极区域分离的胞质组分对 SULT1A1 和 1A3 亚型进行免疫印迹分析。 SULT1A1 表达在小脑、枕叶和额叶分离的细胞质部分中最高，而 SULT1A3 表达在颞上回、海马和颞叶的细胞质中最高。通过免疫组织化学分析，在所有研究的大脑区域中都发现了神经元和神经胶质细胞中的 SULT1A1 和 SULT1A3 免疫反应性。 SULT1A1 已知可催化小酚的代谢，而 SULT1A3 可硫酸化儿茶酚胺神经递质。由于 SULT1A1 和 1A3 具有不同的底物特异性，SULT1A 亚型的表达模式和细胞定位的差异可能与其选择性底物在不同脑区域的分布和功能有关。
Cytosolic sulfotransferases (SULTs) are a family of Phase II drug-metabolizing enzymes that catalyze the transfer of a sulfonate group from 3'-phosphoadenosine 5'-phosphosulfate to endogenous and xenobiotic compounds. Several SULT isoform messages have been detected in the human brain; however, protein expression patterns have not been characterized. Immunoblot analysis of the SULT1A1 and 1A3 isoforms was carried out with cytosolic fractions isolated from superior temporal gyrus, hippocampus, cerebellum, occipital pole, frontal pole, and temporal pole regions of normal adult human brains. SULT1A1 expression was highest in cytosolic fractions isolated from cerebellum, occipital, and frontal lobes, whereas, SULT1A3 expression was highest in cytosol from superior temporal gyrus, hippocampus, and temporal lobe. SULT1A1 and SULT1A3 immunoreactivities were found in both neurons and glial cells by immunohistochemical analysis in all brain regions studied. SULT1A1 is known to catalyze the metabolism of small phenols, whereas SULT1A3 sulfates catecholamine neurotransmitters. Because SULT1A1 and 1A3 have distinct substrate specificities, the differences in expression pattern and cellular localization of the SULT1A isoforms are probably associated with the distribution and function of their selective substrates in the different brain regions.