Cholesterol Sulfate (sodium salt) was first isolated from human plasma in 1965 and found to be present in a concentration of 300 μg/100 ml [1]. The apparent validity of this initial value was soon confirmed by reports of plasma cholesterol sulfate levels involving a limited number of subjects that ranged from 174 to 328 μg/100 ml [2,3].
Cholesterol Sulfate (sodium salt) has the ability to trigger the intrinsic blood coagulation system by activating Factor XII, an action that is not shared by other steroid sulfates or by unconjugated cholesterol. Cholesterol sulfate activates prekallikrein in the presence of Factor XII [4]. Cholesterol sulfate activates multiple epidermal protein kinase C isozymes, especially the ε, Η, and ζ isoforms [5].In vitro, cholesterol sulfate is a novel activator of the Η isoform of protein kinase C, and in so doing is more potent than phosphatidylserine plus phorbol ester [6]. Thrombin and plasmin, serine proteases that play essential roles in blood clotting and fibrinolysis, respectively, are potently inhibited by cholesterol sulfate [7].
Cholesterol Sulfate (sodium salt) (100 μM 2 h) pretreatment resulted in substantially attenuated anti-CD3-induced CD3ζ phosphorylation, Cholesterol Sulfate specifically interacts with the TCR to inhibit transmembrane signaling without interfering with downstream components of the signaling pathway [8]. A strong reduction in the (T cell antigen receptor) TCR nanoclusters extracted from Cholesterol Sulfate-treated 5C.C7 T cells [8]. Increasing the amount of Cholesterol Sulfate (20 μl 25 mM) in the thymus of mice by intrathymic injection led to a decrease in the number of total thymocytes [8].
References:
[1]. Drayer NM, Lieberman S. Isolation of cholesterol sulfate from human blood and gallstones. Biochemical and biophysical research communications. 1965 Jan 4;18(1):126-30.
[2]. Gurpide E, Roberts KD, Welch MT, Bandy L, Lieberman S. Studies on the metabolism of blood-borne cholesterol sulfate. Biochemistry. 1966 Oct 1;5(10):3352-62.
[3]. Winter JS, Bongiovanni AM. Identification of cholesterol sulfate in urine and plasma of normal and hypercholesterolemic subjects. The Journal of Clinical Endocrinology & Metabolism. 1968 Jun 1;28(6):927-30.
[4]. Shimada T, Kato H, Iwanaga S, Iwamori M, Nagai Y. Activation of factor XII and prekallikrein with cholesterol sulfate. Thrombosis research. 1985 Apr 1;38(1):21-31.
[5]. Denning MF, Kazanietz MG, Blumberg PM, Yuspa SH. Cholesterol sulfate activates multiple protein kinase C isoenzymes and induces granular cell differentiation in cultured murine keratinocytes. Cell Growth and Differentiation-Publication American Association for Cancer Research. 1995 Dec 1;6(12):1619-26.
[6]. Ikuta T, Chida K, Tajima O, Matsuura Y, Iwamori M, Ueda Y, Mizuno K, Ohno S, Kuroki T. Cholesterol sulfate, a novel activator for the eta isoform of protein kinase C. Cell Growth & Differentiation: the Molecular Biology Journal of the American Association for Cancer Research. 1994 Sep 1;5(9):943-7.
[7]. Iwamori M, Iwamori Y, Ito N. Regulation of the activities of thrombin and plasmin by cholesterol sulfate as a physiological inhibitor in human plasma. The Journal of Biochemistry. 1999 Mar 1;125(3):594-601.
[8]. Wang F, Beck-García K, Zorzin C, et al. Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol[J]. Nature immunology, 2016, 17(7): 844-850.
硫酸胆固醇（Cholesterol Sulfate (sodium salt)）于 1965 年首次从人体血浆中分离出来，浓度为 300 μg/100 ml [1]。涉及有限数量受试者的血浆胆固醇硫酸盐水平范围为 174 至 328 μg/100 ml 的报告很快证实了该初始值的明显有效性[2,3]。
硫酸胆固醇（Cholesterol Sulfate (sodium salt)）能够通过激活因子 XII 触发内在血液凝固系统，这是其他类固醇硫酸盐或未结合的胆固醇所不具有的作用。硫酸胆固醇在因子 XII [4] 存在的情况下激活前激肽释放酶。硫酸胆固醇激活多种表皮蛋白激酶 C 同工酶，尤其是 ε、Ｈ 和 ζ 同工酶[5]。在体外，硫酸胆固醇是蛋白激酶 C 的 Ｈ 同工酶的新型激活剂，并且在这样做比磷脂酰丝氨酸加佛波酯更有效 [6]。凝血酶和纤溶酶以及分别在血液凝固和纤维蛋白溶解中发挥重要作用的丝氨酸蛋白酶，受到硫酸胆固醇的强烈抑制[7]。
硫酸胆固醇（Cholesterol Sulfate (sodium salt))（100 μM 2 小时）预处理导致抗 CD3 诱导的 CD3ζ 磷酸化显着减弱，胆固醇硫酸盐特异性地与 TCR 相互作用以抑制跨膜信号传导，而不干扰信号通路的下游组分 <sup >[8]。从胆固醇硫酸盐处理的 5C.C7 T 细胞中提取的（T 细胞抗原受体）TCR 纳米团簇显着减少 [8]。通过胸腺内注射增加小鼠胸腺中硫酸胆固醇 (20 μl 25 mM) 的量导致总胸腺细胞数量减少[8]。