Strott Charles A, Higashi Yuko
Section on Steroid Regulation, Endocrinology and Reproduction Research Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892-4510, USA.
J Lipid Res. 2003 Jul;44(7):1268-78. doi: 10.1194/jlr.R300005-JLR200. Epub 2003 May 1.
Cholesterol sulfate is quantitatively the most important known sterol sulfate in human plasma, where it is present in a concentration that overlaps that of the other abundant circulating steroid sulfate, dehydroepiandrosterone (DHEA) sulfate. Although these sulfolipids have similar production and metabolic clearance rates, they arise from distinct sources and are metabolized by different pathways. While the function of DHEA sulfate remains an enigma, cholesterol sulfate has emerged as an important regulatory molecule. Cholesterol sulfate is a component of cell membranes where it has a stabilizing role, e.g., protecting erythrocytes from osmotic lysis and regulating sperm capacitation. It is present in platelet membranes where it supports platelet adhesion. Cholesterol sulfate can regulate the activity of serine proteases, e.g., those involved in blood clotting, fibrinolysis, and epidermal cell adhesion. As a result of its ability to regulate the activity of selective protein kinase C isoforms and modulate the specificity of phosphatidylinositol 3-kinase, cholesterol sulfate is involved in signal transduction. Cholesterol sulfate functions in keratinocyte differentiation, inducing genes that encode for key components involved in development of the barrier. The accumulating evidence demonstrating a regulatory function for cholesterol sulfate appears solid; the challenge now is to work out the molecular mechanisms whereby this interesting molecule carries out its various roles.
硫酸胆固醇在人体血浆中是已知数量上最重要的甾醇硫酸盐，其在血浆中的浓度与另一种丰富的循环类固醇硫酸盐硫酸脱氢表雄酮（DHEA）的浓度重叠。虽然这些硫脂具有相似的产生和代谢清除率，但它们来源于不同的途径并通过不同的代谢途径进行代谢。虽然硫酸脱氢表雄酮的功能仍然是个谜，但硫酸胆固醇已成为一种重要的调节分子。硫酸胆固醇是细胞膜的组成成分，在其中具有稳定作用，例如保护红细胞免受渗透性裂解并调节精子获能。它存在于血小板膜中，在那里支持血小板黏附。硫酸胆固醇可以调节丝氨酸蛋白酶的活性，例如参与血液凝固、纤维蛋白溶解和表皮细胞黏附的那些丝氨酸蛋白酶。由于其具有调节选择性蛋白激酶C亚型活性和调节磷脂酰肌醇3激酶特异性的能力，硫酸胆固醇参与信号转导。硫酸胆固醇在角质形成细胞分化中起作用，诱导编码参与屏障形成关键成分的基因。越来越多的证据表明硫酸胆固醇具有调节功能，这一点似乎确凿无疑；现在面临的挑战是弄清楚这个有趣的分子发挥其各种作用的分子机制。
