van Reyk David M, Brown Andrew J, Hult'en Lillemor Mattsson, Dean Roger T, Jessup Wendy
Department of Medical and Molecular Biosciences, University of Technology, Sydney, Australia.
Redox Rep. 2006;11(6):255-62. doi: 10.1179/135100006X155003.
Oxysterols are the 27-carbon products of cholesterol oxidation by both enzymic and non-enzymic mechanisms. Their roles in cholesterol homeostasis, as well as in diseases in which oxidative damage and lipid peroxidation are implicated (e.g. atherosclerosis), have been investigated extensively. However, there are a number of important considerations regarding the physiological/pathophysiological functions and activities of the different oxysterols. First, in both normal and diseased tissues, the levels of oxysterols are very low when compared to the native sterol. Also, when assessing studies that have measured the levels of oxysterols in biological samples, there must be careful consideration as to the method of sample isolation, storage and sampling. This is because of the potential generation or loss of oxysterols during these procedures. Additionally, the relevance of in vitro studies which examine the effects of oxysterols upon cell function should be judged as to cellular oxysterol content (both in terms of the levels of oxysterol and the degree of esterification) resulting from the oxysterol treatment. We present evidence that the means by which oxysterol is delivered in vitro determines whether the oxysterol content reflects what has been found in vivo. Studies identifying the specific cellular targets of oxysterol indicate that several oxysterols may be regulators of cellular lipid metabolism via control of gene transcription.
氧化甾醇是胆固醇通过酶促和非酶促机制氧化生成的含27个碳原子的产物。它们在胆固醇稳态以及与氧化损伤和脂质过氧化有关的疾病（如动脉粥样硬化）中的作用已得到广泛研究。然而，关于不同氧化甾醇的生理/病理生理功能和活性，有一些重要的考虑因素。首先，在正常组织和患病组织中，与天然甾醇相比，氧化甾醇的水平都非常低。此外，在评估测量生物样品中氧化甾醇水平的研究时，必须仔细考虑样品的分离、储存和取样方法。这是因为在这些过程中氧化甾醇可能会产生或损失。另外，对于研究氧化甾醇对细胞功能影响的体外研究，其相关性应根据氧化甾醇处理导致的细胞氧化甾醇含量（包括氧化甾醇水平和酯化程度）来判断。我们提供的证据表明，体外递送氧化甾醇的方式决定了氧化甾醇含量是否反映体内所发现的情况。确定氧化甾醇特定细胞靶点的研究表明，几种氧化甾醇可能通过控制基因转录来调节细胞脂质代谢。
