5-cholesten-3, 25-diol 3-sulfate Has Potential to Serve as New Medication for Therapy of Inflammator

来源 :中国上海第七届国际新药发明科技年会 | 被引量 : 0次 | 上传用户:clond
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  Disordered lipid metabolism is always closely linked to inflammation.However,mechanisms of coordinate regulation of lipid metabolism and inflammation are unknown.Oxygenated cholesterols,oxysterols,appear to be the key regulatory molecules involved in lipid metabolism and inflammation.When cholesterol delivered to mitochondria was increased by overexpression of the transporter StarD1 in hepatocytes,oxysterols,a novel regulatory oxysterol,5-cholesten-3,25-diol 3-sulfate (25HC3S),were accumulated in the nuclei.Addition of 25HC3S to hepatocytes and macrophages in culture markedly decreased nuclear liver oxysterol receptor (LXR) protein levels but increased nuclear peroxisome proliferator-activated receptor gamma (PPARg) levels,followed by dose-and time-dependent decreases in nuclear sterol response element binding protein-1 (SREBP-1) protein and its mRNA levels.25HC3S also led to a decrease in the expression of SREBP-1 responsive genes including acetyl CoA carboxylase-1 (ACC-1) and fatty acid synthase (FAS),key enzymes involved in fatty acid synthesis with a subsequent decrease in intracellular lipid levels.
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