氧化固醇作为胆固醇动态平衡的非基因组调节剂。
Oxysterols as non-genomic regulators of cholesterol homeostasis.
机构信息
Diabetic Cardiovascular Disease Center, Washington University School of Medicine, St Louis, MO 63110, USA.
出版信息
Trends Endocrinol Metab. 2012 Mar;23(3):99-106. doi: 10.1016/j.tem.2011.12.002. Epub 2012 Jan 11.
Abstract
Tight regulation of cellular and plasma cholesterol is crucial to proper cellular functioning because excess free cholesterol is toxic to cells and is associated with atherosclerosis and heart disease. Cellular cholesterol homeostasis is regulated by enzymatically formed oxygenated cholesterol derivatives termed oxysterols. Although the effects of oxysterols on transcriptional pathways are well described, the non-transcriptional mechanisms through which oxysterols acutely modulate cellular cholesterol levels are less well understood. We present emerging evidence suggesting that the membrane biophysical properties of oxysterols underlie their acute cholesterol-regulatory functions and discuss the relevance of these acute effects to cholesterol overload in physiological and pathophysiological states.
摘要
细胞和血浆胆固醇的严格调节对细胞的正常功能至关重要，因为过量的游离胆固醇对细胞有毒，并且与动脉粥样硬化和心脏病有关。细胞胆固醇稳态由酶形成的含氧胆固醇衍生物（称为氧化固醇）调节。尽管氧化固醇对转录途径的影响已得到很好的描述，但氧化固醇急性调节细胞胆固醇水平的非转录机制还不太清楚。我们提出了一些新的证据，表明氧化固醇的膜生物物理特性是其急性胆固醇调节功能的基础，并讨论了这些急性效应与生理和病理状态下胆固醇过载的相关性。
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