Magnesium tanshinoate B protects endothelial cells against oxidized lipoprotein-induced apoptosis
Magnesium tanshinoate B protects endothelial cells against oxidized lipoprotein-induced apoptosis
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DOI：
10.1139/y07-096
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发表时间：
2007-11-01
影响因子：
2.1
通讯作者：
Siow, Yaw L.
中科院分区：
文献类型：
--
作者：
Au-Yeung, Kathy K. W.;Karmin, O.;Siow, Yaw L.
c-Jun氨基末端激酶（JNK）信号通路的激活在诱导细胞凋亡中起重要作用。我们之前报道过，从中草药丹参中纯化的化合物丹参酸镁B（MT B）可以抑制缺血/再灌注诱导的心脏心肌细胞凋亡。本研究的目的是调查MTB是否可以防止氧化脂蛋白诱导的内皮细胞凋亡。将人脐静脉内皮细胞（HUVECs）与铜氧化极低密度脂蛋白（Cu-OxVLDL）或铜氧化低密度脂蛋白（Cu-OxLDL）共同孵育。用Cu-OxVLDL或Cu-OxLDL处理细胞导致JNK活性增加3倍。Cu-OxVLDL或Cu-OxLDL处理后细胞色素c释放量和caspase-3活性均显著升高，提示细胞凋亡的发生。MTB的存在能够消除Cu-OxVLDL或Cu-OxLDL诱导的JNK激活、细胞色素c释放和caspase-3激活，从而显着减少内皮细胞的凋亡。这项研究的数据表明，氧化脂蛋白诱导内皮细胞凋亡。我们推测MTB对JNK信号通路的抑制是保护这些细胞免受氧化脂蛋白诱导的凋亡的关键机制。
The activation of c-Jun N-terminal kinase (JNK) signaling pathway plays an important role in the induction of cell apoptosis. We previously reported that magnesium tanshinoate B (MTB), a compound purified from a Chinese herb danshen (Salvia miltiorrhiza), could inhibit ischemia/reperfusion-induced myocyte apoptosis in the heart. The objective of the present study was to investigate whether MTB can prevent oxidized lipoprotein-induced apoptosis in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were incubated with copper-oxidized very low density lipoprotein (Cu-OxVLDL) or copper-oxidized low density lipoprotein (Cu-OxLDL). Treatment of cells with Cu-OxVLDL or Cu-OxLDL resulted in a 3-fold increase in the JNK activity. The amount of cytochrome c released and the activity of caspase-3 in cells treated with Cu-OxVLDL or Cu-OxLDL were significantly elevated, indicating the occurrence of apoptosis. The presence of MTB was able to abolish the JNK activation, cytochrome c release, and caspase-3 activation induced by Cu-OxVLDL or Cu-OxLDL, resulting in a marked reduction in apoptosis in endothelial cells. The data from this study indicate that oxidized lipoproteins induce apoptosis in endothelial cells. We postulate that the inhibition of the JNK signaling pathway by MTB is a key mechanism that protects these cells from oxidized lipoprotein-induced apoptosis.