Larsson Hanna, Böttiger Ylva, Iuliano Luigi, Diczfalusy Ulf
Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Huddinge, SE-141 86 Stockholm, Sweden.
Free Radic Biol Med. 2007 Sep 1;43(5):695-701. doi: 10.1016/j.freeradbiomed.2007.04.033. Epub 2007 May 10.
The oxysterols 7beta-hydroxycholesterol and 7-ketocholesterol are cholesterol autoxidation products. These two oxysterols are formed as a result of low density lipoprotein oxidation and in a study on biomarkers for oxidative stress in patients with atherosclerosis, 7beta-hydroxycholesterol was found to be the strongest predictor of progression of carotid atherosclerosis. Interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol in vitro has been reported recently, using recombinant 11beta-hydroxysteroid dehydrogenase or rodent liver microsomes. In this study deuterium-labeled 7beta-hydroxycholesterol or 7-ketocholesterol was administered intravenously to two healthy volunteers and blood samples were collected at different time points. The mean half-life for elimination of 7beta-hydroxycholesterol from the circulation was estimated to be 1.9 h. The corresponding half-life for 7-ketocholesterol was estimated to be 1.5 h. Infusion of deuterium-labeled 7-ketocholesterol resulted in labeling of 7beta-hydroxycholesterol and vice versa. In addition, the biological within-day and between-day variations of the two oxysterols were determined. In summary, the present investigation clearly shows an interconversion of 7beta-hydroxycholesterol and 7-ketocholesterol in humans.
氧化甾醇7β-羟基胆固醇和7-酮胆固醇是胆固醇的自氧化产物。这两种氧化甾醇是低密度脂蛋白氧化的结果，并且在一项关于动脉粥样硬化患者氧化应激生物标志物的研究中，发现7β-羟基胆固醇是颈动脉粥样硬化进展的最强预测指标。最近有报道称，利用重组11β-羟基类固醇脱氢酶或啮齿动物肝脏微粒体，7β-羟基胆固醇和7-酮胆固醇在体外可以相互转化。在本研究中，给两名健康志愿者静脉注射氘标记的7β-羟基胆固醇或7-酮胆固醇，并在不同时间点采集血样。循环中7β-羟基胆固醇消除的平均半衰期估计为1.9小时。7-酮胆固醇的相应半衰期估计为1.5小时。注入氘标记的7-酮胆固醇会导致7β-羟基胆固醇被标记，反之亦然。此外，还测定了这两种氧化甾醇在日内和日间的生物学变异。总之，本研究清楚地表明了7β-羟基胆固醇和7-酮胆固醇在人体内可以相互转化。
