首页> 外文期刊>The Journal of Nutritional Biochemistry >Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF- alpha.
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Epigallocatechin gallate induces expression of heme oxygenase-1 in endothelial cells via p38 MAPK and Nrf-2 that suppresses proinflammatory actions of TNF- alpha.

机译:表没食子儿茶素没食子酸酯通过抑制TNF-α的促炎作用的p38 MAPK和Nrf-2在内皮细胞中诱导血红素加氧酶-1的表达。

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Epigallocatechin gallate (EGCG), the major polyphenol in green tea, acutely stimulates production of nitric oxide (NO) from vascular endothelium to reduce hypertension and improve endothelial dysfunction in spontaneously hypertensive rats. Herein, we explored additional mechanisms whereby EGCG may mediate beneficial cardiovascular actions. When compared with vehicle-treated controls, EGCG treatment (2.5 muM, 8 h) of human aortic endothelial cells (HAEC) caused a approx. equal to three-fold increase in heme oxygenase-1 (HO-1) mRNA and protein with comparable increases in HO-1 activity. This was unaffected by pretreatment of cells with wortmannin, LY294002, PD98059 or L-NAME (PI 3-kinase, MEK and NO synthase inhibitors, respectively). Pretreatment of HAEC with SB203580 (p38 MAPK inhibitor) or siRNA knockdown of p38 MAPK completely blocked EGCG-stimulated induction of HO-1. EGCG treatment also inhibited tumor-necrosis-factor- alpha-stimulated expression of vascular cell adhesion molecule (VCAM)-1 and decreased adhesion of monocytes to HAEC. siRNA knockdown of HO-1, p38 MAPK or Nrf-2 blocked these inhibitory actions of EGCG. In HAEC transiently transfected with a human HO-1 promoter luciferase reporter (or an isolated Nrf-2 responsive region), luciferase activity increased in response to EGCG. This was inhibitable by SB203580 pretreatment. EGCG-stimulated expression of HO-1 and Nrf-2 was blocked by siRNA knockdown of Nrf-2 or p38 MAPK. Finally, liver from mice chronically treated with EGCG had increased HO-1 and decreased VCAM-1 expression. Thus, in vascular endothelium, EGCG requires p38 MAPK to increase expression of Nrf-2 that drives expression of HO-1, resulting in increased HO-1 activity. Increased HO-1 expression may underlie anti-inflammatory actions of EGCG in vascular endothelium that may help mediate beneficial cardiovascular actions of green tea
机译:没食子儿茶素没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯没食子酸酯。在本文中,我们探索了EGCG可能介导有益心血管作用的其他机制。与媒介物对照相比,人主动脉内皮细胞(HAEC)的EGCG处理(2.5μM,8小时)引起了等于血红素加氧酶-1(HO-1)mRNA和蛋白质增加了三倍,而HO-1活性却相当。这不受渥曼青霉素,LY294002,PD98059或L-NAME(分别为PI 3-激酶,MEK和NO合酶抑制剂)预处理的影响。用SB203580(p38 MAPK抑制剂)预处理HAEC或p38 MAPK的siRNA敲低完全阻断了EGCG刺激的HO-1诱导。 EGCG治疗还抑制了肿瘤坏死因子-α刺激的血管细胞粘附分子(VCAM)-1的表达,并降低了单核细胞与HAEC的粘附。 HO-1,p38 MAPK或Nrf-2的siRNA敲低阻断了EGCG的这些抑制作用。在人HO-1启动子荧光素酶报道基因(或分离的Nrf-2响应区)瞬时转染的HAEC中,荧光素酶活性随EGCG的增加而增加。 SB203580预处理可以抑制这种情况。 EGCG刺激的HO-1和Nrf-2表达被Nrf-2或p38 MAPK的siRNA敲低所阻断。最后,用EGCG长期治疗的小鼠肝脏的HO-1含量增加,VCAM-1的表达降低。因此,在血管内皮中,EGCG需要p38 MAPK来增加驱动HO-1表达的Nrf-2的表达,从而提高HO-1的活性。 HO-1表达增加可能是血管内皮EGCG抗炎作用的基础,可能有助于介导绿茶有益的心血管作用

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