Isoflavone genistein protects human vascular endothelial cells against tumor necrosis factor-alpha-induced apoptosis through the p38beta mitogen-activated protein kinase.
Isoflavone genistein protects human vascular endothelial cells against tumor necrosis factor-alpha-induced apoptosis through the p38beta mitogen-activated protein kinase.
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异黄酮染料木黄酮通过p38beta促丝分裂原激活的蛋白激酶保护人血管内皮细胞免受肿瘤坏死因子 - α诱导的凋亡。
DOI：
10.1007/s10495-008-0283-9
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发表时间：
2009-01
期刊：
影响因子：
7.2
通讯作者：
Liu, Dongmin
中科院分区：
文献类型：
--
作者：
Si, Hongwei;Liu, Dongmin
异黄酮染料木黄酮可能对血管功能有有益作用，但其机制尚不清楚。本研究探讨染料木黄酮对肿瘤坏死因子-α（TNF-α）诱导的血管内皮细胞凋亡的保护作用。通过caspase-3激活、7-氨基放线菌素D染色、原位凋亡细胞检测和DNA梯状条带分析，我们发现染料木黄酮显著抑制TNF-α诱导的人主动脉内皮细胞（HAECs）凋亡。染料木黄酮的抗凋亡作用与Bcl-2蛋白表达及其启动子活性的增强有关。细胞外信号调节激酶1/2，蛋白激酶A，或雌激素受体的抑制对染料木黄酮的细胞保护作用没有影响。然而，抑制p38丝裂原活化蛋白激酶（p38）完全取消了这种染料木黄酮的效果。因此，用染料木黄酮刺激HAEC导致p38β而不是p38α的快速活化。这些结果提供了证据，染料木黄酮作为一种存活因子的血管内皮细胞，以保护细胞免受凋亡通过激活p38β。保护内皮细胞单层的功能完整性可能是金雀异黄素发挥其血管保护作用的一个重要机制。
Isoflavone genistein may have beneficial effects on vascular function, but the mechanism is unclear. Here, we investigated whether genistein protects vascular endothelial cells (ECs) against apoptosis induced by tumor necrosis factor-α (TNF-α). We show that genistein significantly inhibited TNF-α-induced apoptosis in human aortic endothelial cells (HAECs) as determined by caspase-3 activation, 7-amino actinomycin D staining, in situ apoptotic cell detection and DNA laddering. The anti-apoptotic effect of genistein was associated with an enhanced expression of Bcl-2 protein and its promoter activity. Inhibition of extracellular signal-regulated kinase 1/2, protein kinase A, or estrogen receptors had no effect on the cytoprotective effect of genistein. However, inhibition of p38 mitogen activated protein kinase (p38) completely abolished this genistein effect. Accordingly, stimulation of HAECs with genistein resulted in rapid activation of p38β, but not p38α. These findings provide the evidence that genistein acts as a survival factor for vascular ECs to protect cells against apoptosis via activation of p38β. Preservation of the functional integrity of the endothelial monolayer may represent an important mechanism by which genistein exerts its vasculoprotective effect.
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影响因子：
4.2
作者：
Goodman-Gruen, D;Kritz-Silverstein, D
通讯作者：
Kritz-Silverstein, D
DOI：
10.1258/136218006777525776
发表时间：
2006-06-01
期刊：
The journal of the British Menopause Society
影响因子：
--
作者：
Cassidy, Aedin;Hooper, Lee
通讯作者：
Hooper, Lee
影响因子：
15.9
作者：
Badrichani, AZ;Stroka, DM;Ferran, C
通讯作者：
Ferran, C
影响因子：
3.2
作者：
Chodon, Dechen;Ramamurty, Nalini;Sakthisekaran, D.
通讯作者：
Sakthisekaran, D.
影响因子：
6.7
作者：
Honore, EK;Williams, JK;Clarkson, TB
通讯作者：
Clarkson, TB