Trougakos Ioannis P, Poulakou Maria, Stathatos Marios, Chalikia Anastasia, Melidonis Andreas, Gonos Efstathios S
Laboratory of Molecular and Cellular Ageing, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48 Vas. Constantinou Avenue, Athens 11635, Greece.
Exp Gerontol. 2002 Oct-Nov;37(10-11):1175-87. doi: 10.1016/s0531-5565(02)00139-0.
Clusterin/apolipoprotein J (hereafter ApoJ) is a conserved secreted glycoprotein expressed by a wide array of tissues and being implicated in several physiological processes. ApoJ has been shown to associate with both normal in vitro aging, namely replicative senescence, as well as with stress induced premature senescence. In vivo, the protein is up-regulated in many severe physiological disturbances that relate to advanced aging, including accumulation in the artery wall during the development of atherosclerosis. In the current report we have expanded our previous studies that focus in the biological role of ApoJ during aging by addressing two interrelated issues: (a) we have examined the potential ApoJ association with in vivo aging and (b) we have studied whether its accumulation in the artery wall during the development of atherosclerosis is combined with a measurable increase of its serum levels, as well as, whether a similar effect occurs in diseases, such as diabetes type II, known to represent major risk factors of atherosclerosis. By combining a sandwich ELISA assay and immunoblotting analysis we demonstrate a measurable increase of ApoJ serum levels with age in males and provide evidence that, as compared to healthy donors, the serum ApoJ amount increases significantly in diabetic type II patients and in patients suffering from either a developing coronary heart disease, or myocardial infarction. The highest serum ApoJ levels were found during myocardial infarction but no correlation was observed with the number of vessels with documented atherosclerotic damage. In conclusion, this report illustrates that ApoJ accumulation in serum is probably coupled to a generalized stress mediated induction mechanism that is specifically related to certain diseases; moreover these data raise the possibility that elevated ApoJ levels in serum may represent a strong indication of vascular damage.
簇集素/载脂蛋白J（以下简称ApoJ）是一种保守的分泌型糖蛋白，由多种组织表达，并参与多种生理过程。ApoJ已被证明与体外正常衰老（即复制性衰老）以及应激诱导的早衰有关。在体内，该蛋白在许多与衰老相关的严重生理紊乱中上调，包括动脉粥样硬化发展过程中在动脉壁的积聚。在本报告中，我们扩展了之前关于ApoJ在衰老过程中的生物学作用的研究，探讨了两个相互关联的问题：（a）我们研究了ApoJ与体内衰老的潜在关联；（b）我们研究了在动脉粥样硬化发展过程中其在动脉壁的积聚是否伴随着血清水平的显著升高，以及在已知为动脉粥样硬化主要危险因素的疾病（如II型糖尿病）中是否也会出现类似效应。通过结合夹心ELISA检测和免疫印迹分析，我们证明男性血清中ApoJ水平随年龄增长而显著升高，并提供证据表明，与健康供体相比，II型糖尿病患者以及患有冠心病或心肌梗死的患者血清ApoJ含量显著增加。心肌梗死期间血清ApoJ水平最高，但与有动脉粥样硬化损伤记录的血管数量无关。总之，本报告表明血清中ApoJ的积累可能与一种普遍的应激介导诱导机制相关，该机制与某些特定疾病密切相关；此外，这些数据增加了血清中ApoJ水平升高可能是血管损伤强烈指征的可能性。
