Disease relevance of CHOLESTEROL-SULFATE

• Recessive x-linked ichthyosis: role of cholesterol-sulfate accumulation in the barrier abnormality [1].
• Treatment of experimental invasive aspergillosis with novel amphotericin B/cholesterol-sulfate complexes [2].
• To elucidate the functional significance of sulfated lipids in the digestive tract, we determined the effect of CS and I3SO3-GalCer on the activities of pancreatic and Pseudomonas aeruginosa elastases and found that both characteristically inhibited the pancreatic elastase but not the P. aeruginosa elastase [3].

High impact information on CHOLESTEROL-SULFATE

• Thus, LXR and PPAR activators regulate the expression of SULT2B1b, the key enzyme in the synthesis of CS, which is a potent regulator of epidermal differentiation and corneocyte desquamation [4].
• Cholesterol sulfotransferase type 2B isoform 1b (SULT2B1b) is a key enzyme in the synthesis of cholesterol sulfate (CS), a critical regulator of keratinocyte differentiation and desquamation, as well as a mediator of barrier homeostasis [4].
• The acute LD50 of amphotericin B-deoxycholate was 5.1 mg/kg versus 20 mg/kg for the amphotericin/cholesterol-sulfate complexes [2].
• However, 3-hr incubation with HBCD plus ChS or with 1 mM ChS alone decreased the percentage of sperm undergoing the induced acrosome reaction without significantly affecting viability when compared to the control [5].
• Biochemical characterization of cholesterol-3-sulfate as the sole effector for the phosphorylation of HMG1 by casein kinase I in vitro [6].

Biological context of CHOLESTEROL-SULFATE

• In contrast, further supplement of HBCD with cholesterol-3-sulfate (a cholesterol analogue) resulted in a decrease in all the aforementioned criteria, suggesting that the ability of HBCD to protect spermatozoa from cold shock injury is blocked by saturating the cholesterol binding sites of HBCD [7].
• Reflected by the increase in activity, CS was detected in fetal skin at day 15, and the concentration in epidermis significantly increased during the gestation period, reaching maximum level at day 17 [8].
• The effects of cholesterol-3-sulfate (CH-3S) on the phosphorylation of human C3a (hC3a) in vitro and on the ability of hC3a to induce vascular permeability in rats [9].

Anatomical context of CHOLESTEROL-SULFATE

• Spermatozoa were exposed to MBCD or a combination of MBCD and cholesterol-3-sulfate over a period of 3 hours while being cooled slowly from 25 degrees C to 5 degrees C, and were subsequently cryopreserved by the pellet method [10].
• We also present evidence that the recognition of sulfatides, cholesterol-3-sulfate, or other cross-reactive sulfated macromolecules by region II may be required during sporozoite invasion of liver cells [11].
• Thus, CS and I3SO3-GalCer in the digestive tracts of mammals were shown to function as epithelial inhibitors of pancreatic elastase [3].
• RESULTS: Human gastric epithelium contained both sulfatide and cholesterol sulfate (CS) as sulfolipids, which were also detected in gastric fluid, showing their stable natures in the gastric fluid [12].
• Here, we show such a novel function of the most abundant sulfated sterol in human blood, cholesterol sulfate (CS), to suppress LT production in human polymorphonuclear leukocytes (PMNL) and Mono Mac6 cells [13].

Gene context of CHOLESTEROL-SULFATE

• Although the insoluble CS sulfatase in the microsomal fraction remained at a relatively constant level, the soluble CST in the cytosol fraction showed a 6-fold increase from day 14 to day 16, and the activity decreased continuously in the following period, reaching one forty-sixth of the maximum level at 4-months-old mice [8].
• Activation of C-kinase eta through its cholesterol-3-sulfate-dependent phosphorylation by casein kinase I in vitro [14].
• Cholesterol increased the effect of CS on 5-LO product synthesis [13].
• The system is based on making cells dependent on cholesterol-sulfate as the sole source of cholesterol, allowing only STS+ cells to grow [15].

References