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首页> 外文期刊>Biochemistry >Chronic Cholesterol Depletion Using Statin Impairs the Function and Dynamics of Human Serotonin1A Receptors
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Chronic Cholesterol Depletion Using Statin Impairs the Function and Dynamics of Human Serotonin1A Receptors

机译:使用他汀类药物的慢性胆固醇消耗会破坏人血清素1A受体的功能和动力学。

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Statins are potent inhibitors of HMG-CoA reductase, the key rate-limiting enzyme in cholesterolnbiosynthesis, and are some of the best selling drugs globally.We have explored the effect of chronic cholesterolndepletion induced by mevastatin on the function of human serotonin1A receptors expressed in CHO cells.nAn advantage with statins is that cholesterol depletion is chronic which mimics physiological conditions. Ournresults show a significant reduction in the level of specific ligand binding and G-protein coupling to serotonin1Anreceptors upon chronic cholesterol depletion, although the membrane receptor level is not reduced at all.nInterestingly, replenishment of mevastatin-treated cells with cholesterol resulted in the recovery of specificnligand binding and G-protein coupling. Treatment of cells expressing serotonin1A receptors with mevastatinnled to a decrease in the diffusion coefficient and an increase in the mobile fraction of the receptor, as deter-nmined by fluorescence recovery after photobleaching measurements. To the best of our knowledge, thesenresults constitute the first report describing the effect of chronic cholesterol depletion on the organization andnfunction of a G-protein-coupled neuronal receptor. Our results assume significance in view of recent reportsnhighlighting the symptoms of anxiety and depression in humans upon statin administration, and the role ofnserotonin1A receptors in anxiety and depression.
机译:他汀类药物是HMG-CoA还原酶的强效抑制剂,HMG-CoA还原酶是胆固醇生物合成中的关键限速酶,并且是全球最畅销的药物。我们已经研究了美伐他汀诱导的慢性胆固醇消耗对CHO中表达的人血清素1A受体功能的影响。他汀类药物的一个优势是胆固醇的消耗是慢性的,可以模拟生理状况。我们的研究结果显示,尽管完全没有降低膜受体水平,但慢性胆固醇耗尽后特异性配体结合和G蛋白与血清素1受体的结合水平显着降低。n有趣的是,美伐他汀处理过的细胞补充了胆固醇,导致胆固醇的恢复。特异性配体结合和G蛋白偶联。用美伐他汀处理表达5-羟色胺1A受体的细胞后,扩散系数降低,受体的活动分数增加,这是通过光漂白测量后的荧光恢复来确定的。据我们所知,本研究结果首次描述了慢性胆固醇耗竭对G蛋白偶联神经元受体的组织和功能的影响。鉴于最近的报道强调了他汀类药物给药后人的焦虑和抑郁症状,以及神经素1A受体在焦虑和抑郁中的作用,我们的结果具有重要意义。

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