Miyoshi Noriyuki
Laboratory of Biochemistry, Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan.
J Clin Biochem Nutr. 2018 Mar;62(2):107-114. doi: 10.3164/jcbn.17-109. Epub 2018 Feb 7.
Elevated levels of cholesterol aldehyde, 3β-hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A, also called 5,6-secosterol), and its aldolization product (secosterol-B) have been detected in human atherosclerotic plaques and tissues samples of brains affected by neurodegeneration, such as Alzheimer's disease and Lewy body dementia suggesting that increased formation of these compounds may be associated with inflammation-related diseases. Secosterol-A and secosterol-B, and also further oxidized products seco-A-COOH and seco-B-COOH induce several pro-inflammatory activities . Accumulating evidences demonstrate that the covalent bindings of these secosterols to target proteins seem to be critical to trigger their pro-inflammatory activities. One of the molecular mechanisms of protein adduct formations is that aldehydic function of secosterol-A and secosterol-B is reactive and form Schiff bases with ε- or N-terminal amino groups of proteins. In other cases, it is recently suggested that Michael acceptor moiety formed by the dehydration of not only secosterol-A and secosterol-B but also seco-A-COOH may react with nucleophilic site on target proteins. In this review, I summarize and provide an overview of formation mechanism of secosterols in and , patho- or physiological concentrations in biological and clinical samples, and molecular mechanisms of pro-inflammatory activities of secosterols.
在人类动脉粥样硬化斑块以及受神经退行性疾病影响的脑组织样本（如阿尔茨海默病和路易体痴呆）中，已检测到胆固醇醛、3β - 羟基 - 5 - 氧代 - 5,6 - 开环胆甾烷 - 6 - 醛（开环甾醇 - A，也称为5,6 - 开环甾醇）及其羟醛缩合产物（开环甾醇 - B）水平升高，这表明这些化合物生成增加可能与炎症相关疾病有关。开环甾醇 - A和开环甾醇 - B，以及进一步氧化的产物开环 - A - 羧酸和开环 - B - 羧酸可诱导多种促炎活性。越来越多的证据表明，这些开环甾醇与靶蛋白的共价结合似乎是触发其促炎活性的关键。蛋白质加合物形成的分子机制之一是开环甾醇 - A和开环甾醇 - B的醛基具有反应性，可与蛋白质的ε - 或N - 末端氨基形成席夫碱。在其他情况下，最近有人提出，不仅开环甾醇 - A和开环甾醇 - B，而且开环 - A - 羧酸脱水形成的迈克尔受体部分可能与靶蛋白上的亲核位点发生反应。在这篇综述中，我总结并概述了开环甾醇在[具体内容缺失]中的形成机制、生物和临床样本中的病理或生理浓度以及开环甾醇促炎活性分子机制。
