Liu Shuang, Hou Wei, Qin Hua, Wang Ying
Hubei Center for Disease Control and Prevention, Wuhan, 430079, China.
Department of Gastroenterology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
J Huazhong Univ Sci Technolog Med Sci. 2015 Apr;35(2):200-205. doi: 10.1007/s11596-015-1411-8. Epub 2015 Apr 16.
Oxidized low density lipoprotein (oxLDL) can trigger intracellular production of reactive oxygen species and lipid peroxidation (LPO), and is thought to contribute to initiation and progression of atherosclerosis. In order to understand the correlation between oxLDL and macromolecular damage, we measured levels of LPO-derived miscoding etheno-DNA adducts and LPO-modified proteins in cultured human vascular endothelial and smooth muscle cells after incubation with oxLDL for up to 48 h. A semi-quantative analysis method for 1, N6-ethenodeoxyadenosine (ɛdA) by immunohistochemistry was applied. After oxLDL stimulation, ɛdA-stained nuclei were significantly increased in both endothelial and smooth muscle cells. Similarly, 4-hydroxy-2-nonenal (4-HNE)-modified proteins, as analyzed by immunohistochemistry and Western blotting, were also 3-5 fold increased. It was concluded LPO-derived etheno-DNA adducts and LPO-modified proteins are strongly induced by oxLDL in human vascular endothelial and smooth muscle cells. This macromolecular damage may contribute to the dysfunction of arterial endothelium and the onset of atherosclerosis.
氧化型低密度脂蛋白（oxLDL）可引发细胞内活性氧的产生和脂质过氧化（LPO），并被认为与动脉粥样硬化的发生和发展有关。为了了解oxLDL与大分子损伤之间的关系，我们在培养的人血管内皮细胞和平滑肌细胞中，用oxLDL孵育长达48小时后，测量了LPO衍生的错配乙烯基-DNA加合物和LPO修饰蛋白的水平。应用免疫组织化学方法对1，N6-乙烯基脱氧腺苷（ɛdA）进行半定量分析。oxLDL刺激后，内皮细胞和平滑肌细胞中ɛdA染色的细胞核均显著增加。同样，通过免疫组织化学和蛋白质印迹分析的4-羟基-2-壬烯醛（4-HNE）修饰蛋白也增加了3-5倍。得出的结论是，oxLDL在人血管内皮细胞和平滑肌细胞中强烈诱导LPO衍生的乙烯基-DNA加合物和LPO修饰蛋白。这种大分子损伤可能导致动脉内皮功能障碍和动脉粥样硬化的发生。
