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葡萄籽原花青素 B2 通过调控 GSK3β 磷酸化抑制糖基化终产物诱导的内皮细胞凋亡。

Grape seed procyanidin B2 inhibits advanced glycation end product-induced endothelial cell apoptosis through regulating GSK3β phosphorylation.

机构信息

Key Laboratory of Cardiovascular Proteomics of Shandong Province, Department of Geriatrics, QiLu Hospital of Shandong University, Jinan, Shandong Province, Peoples Republic of China.

出版信息

Cell Biol Int. 2011 Jul;35(7):663-9. doi: 10.1042/CBI20100656.

Abstract

To investigate the effects of GSPB2 (grape seed procyanidin B2) on the apoptosis of HUVECs (human umbilical endothelial cells) induced by AGEs (advanced glycation end products), HUVECs were treated with AGEs (200 μg/ml) in the presence or absence of GSPB2 (2.5, 5.0 and 10.0 μmol/l). Our findings showed that (i) AGEs induced HUVEC apoptosis and up-regulated the expression of caspase-3 activation and lactadherin and reduced the phosphorylation of GSK3β (glycogen synthase kinase 3β) at baseline. (ii) Treatment of HUVEC with GSPB2 significantly inhibited the cell apoptosis and the expression of caspase-3 activation and lactadherin induced by AGEs. Moreover, GSPB2 inhibited intracellular reactive oxygen species in a dose-dependent manner in AGEs-treated cells as determined by flow cytometry. (iii) GSPB2 increased the phosphorylation of GSK3β of HUVEC in response to AGEs. These findings suggest that the signalling pathway involving phosphorylation of GSK3β and lactadherin might play a key role in the endothelial apoptosis. GSPB2 therapy could become an effective approach to battling AGEs-induced endothelial apoptosis.

摘要

为了研究 GSPB2(葡萄籽原花青素 B2)对 AGEs(晚期糖基化终产物)诱导的 HUVECs(人脐静脉内皮细胞)凋亡的影响,将 HUVECs 用 AGEs(200μg/ml)处理,同时存在或不存在 GSPB2(2.5、5.0 和 10.0μmol/l)。我们的研究结果表明:(i)AGEs 诱导 HUVEC 凋亡,并上调 caspase-3 激活和乳粘素的表达,降低 GSK3β(糖原合酶激酶 3β)在基线时的磷酸化。(ii)用 GSPB2 处理 HUVEC 可显著抑制 AGEs 诱导的细胞凋亡和 caspase-3 激活及乳粘素的表达。此外,流式细胞术测定,GSPB2 可抑制 AGEs 处理细胞中活性氧的产生,呈剂量依赖性。(iii)GSPB2 增加了 HUVEC 对 AGEs 反应的 GSK3β磷酸化。这些发现表明,涉及 GSK3β和乳粘素磷酸化的信号通路可能在血管内皮细胞凋亡中起关键作用。GSPB2 治疗可能成为对抗 AGEs 诱导的内皮细胞凋亡的有效方法。

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