Cholesterol and oxysterol sulfates: Pathophysiological roles and analytical challenges

Abstract

Cholesterol and oxysterol sulfates are important regulators of lipid metabolism, inflammation, cell apoptosis, and cell survival. Among the sulfate-based lipids, cholesterol sulfate (CS) is the most studied lipid both quantitatively and functionally. Despite the importance, very few studies have analysed and linked the actions of oxysterol sulfates to their physiological and pathophysiological roles. Overexpression of sulfotransferases confirmed the formation of a range of oxysterol sulfates and their antagonistic effects on liver X receptors (LXRs) prompting further investigations how are the changes to oxysterol/oxysterol sulfate homeostasis can contribute to LXR activity in the physiological milieu. Here, we aim to bring together for novel roles of oxysterol sulfates, the available techniques and the challenges associated with their analysis. Understanding the oxysterol/oxysterol sulfate levels and their pathophysiological mechanisms could lead to new therapeutic targets for metabolic diseases.

The search for disease-modifying agents in decompensated cirrhosis: From drug repurposing to drug discovery

“…They decrease lipid biosynthesis, suppress inflammatory responses, and promote cell survival by acting through epigenetic modification. 130,131 The intravenous administration of one of these oxysterol sulfates, DUR-928, has been evaluated in a pivotal, phase IIA, open-label study enrolling 19 patients with moderate-severe acute alcoholic hepatitis. Based on promising safety and efficacy signals, 132,133 phase IIB studies have now been planned (ClinicalTrials.gov identifiers: NCT03917407 and NCT04563026).…”

Multiple Roles of 25-Hydroxycholesterol in Lipid Metabolism, Antivirus Process, Inflammatory Response, and Cell Survival

“…Cholesterol is a member of the sterol family that plays essential roles in a variety of biological processes [ 1 ]. Under physiological state, cholesterol is mainly metabolized into bile acids and steroid hormones such as estrogens and androgens.…”

Cholesterol Metabolites 25-Hydroxycholesterol and 25-Hydroxycholesterol 3-Sulfate Are Potent Paired Regulators: From Discovery to Clinical Usage

“…can be further sulfated by sulfotransferase 2A1 (SULT2A1) to be oxysterol disulfates [20][21][22]. The most eminent oxysterol sulfate is 25-hydroxycholesterol 3-sulfate (25HC3S), which can be further sulfated by SULT2A1 to 5-cholesten-3β, 25-diol-disulfate (25HCDS).…”

“…Oxysterols can be sulfated by sulfotransferase 2B1b (SULT2B1b) at the 3 position of ring A of cholesterol to be oxysterol 3-sulfates, including 25HC3S, 24HC3S, 27HC3S, as well as Xol3S (cholesterol 3-sulfate) [ 17 , 18 , 19 ], as shown in Figure 1 . Oxysterol sulfate can be further sulfated by sulfotransferase 2A1 (SULT2A1) to be oxysterol disulfates [ 20 , 21 , 22 ]. The most eminent oxysterol sulfate is 25-hydroxycholesterol 3-sulfate (25HC3S), which can be further sulfated by SULT2A1 to 5-cholesten-3β, 25-diol-disulfate (25HCDS).…”