High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors.
High glucose-induced apoptosis in human coronary artery endothelial cells involves up-regulation of death receptors.
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DOI：
10.1186/1475-2840-10-73
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发表时间：
2011-08-04
影响因子：
9.3
通讯作者：
Hattori Y
中科院分区：
文献类型：
--
作者：
Kageyama S;Yokoo H;Tomita K;Kageyama-Yahara N;Uchimido R;Matsuda N;Yamamoto S;Hattori Y
高糖可诱导血管内皮细胞凋亡，这可能是糖尿病血管并发症发生的原因之一。我们评价了死亡受体通路在高糖诱导的人冠状动脉内皮细胞(HCAECs)凋亡中的作用。用含5.6mM、11.1mM和16.7mM葡萄糖的培养液处理HCAEC 24 h，同时加入或不加入肿瘤坏死因子-α。细胞凋亡检测采用DNA片段化方法。用聚合酶链式反应和流式细胞术分析HCAEC死亡受体的表达。此外，利用免疫组织化学技术，对链脲佐菌素-烟酰胺诱导的2型糖尿病小鼠死亡受体的冠状表达进行了评估。HCAECs暴露于高糖后，其肿瘤坏死因子-R1和Fas的表达较正常葡萄糖显著增加。高糖促进HCAEC产生肿瘤坏死因子-α，外源性肿瘤坏死因子-α上调血管内皮细胞肿瘤坏死因子-R1和Fas的表达。高糖诱导的肿瘤坏死因子-R_1和Fas的表达在肿瘤坏死因子-α存在时不能被检测到。用肿瘤坏死因子-1中和肽治疗可显著抑制高糖诱导的内皮细胞凋亡。2型糖尿病小鼠冠状动脉有明显的肿瘤坏死因子-R1和Fas的表达。随着肿瘤坏死因子-α水平的升高，死亡受体肿瘤坏死因子-R1和Fas在高糖环境下内皮细胞表达上调，进而在高糖诱导内皮细胞凋亡中发挥作用。
High glucose can induce apoptosis in vascular endothelial cells, which may contribute to the development of vascular complications in diabetes. We evaluated the role of the death receptor pathway of apoptotic signaling in high glucose-induced apoptosis in human coronary artery endothelial cells (HCAECs). HCAECs were treated with media containing 5.6, 11.1, and 16.7 mM of glucose for 24 h in the presence or absence of tumor necrosis factor (TNF)-α. For detection of apoptosis, DNA fragmentation assay was used. HCAEC expression of death receptors were analyzed by the PCR and flow cytometry methods. Also, using immunohistochemical techniques, coronary expression of death receptors was assessed in streptozotocin-nicotinamide-induced type 2 diabetic mice. Exposure of HCAECs to high glucose resulted in a significant increase in TNF-R1 and Fas expression, compared with normal glucose. High glucose increased TNF-α production by HCAECs and exogenous TNF-α up-regulated TNF-R1 and Fas expression in HCAECs. High glucose-induced up-regulation of TNF-R1 and Fas expression was undetectable in the presence of TNF-α. Treatment with TNF-R1 neutralizing peptides significantly inhibited high glucose-induced endothelial cell apoptosis. Type 2 diabetic mice displayed appreciable expression of TNF-R1 and Fas in coronary vessels. In association with increased TNF-α levels, the death receptors, TNF-R1 and Fas, are up-regulated in HCAECs under high glucose conditions, which could in turn play a role in high glucose-induced endothelial cell apoptosis.
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影响因子：
37.8
作者：
Ho, FM;Liu, SH;Lin-Shiau, SY
通讯作者：
Lin-Shiau, SY
影响因子：
9.3
作者：
El-Seweidy, MM;El-Swefy, SE;Hashem, RM
通讯作者：
Hashem, RM
影响因子：
7.7
作者：
LORENZI, M;NORDBERG, JA;TOLEDO, S
通讯作者：
TOLEDO, S
影响因子：
8.3
作者：
Kobayashi, T;Taguchi, K;Kamata, K
通讯作者：
Kamata, K
影响因子：
7.7
作者：
Dudek, Nadine L.;Thomas, Helen E.;Kay, Thomas W. H.
通讯作者：
Kay, Thomas W. H.