Improvement of vascular dysfunction by argirein through inhibiting endothelial cell apoptosis associated with ET-1/Nox4 signal pathway in diabetic rats.
Improvement of vascular dysfunction by argirein through inhibiting endothelial cell apoptosis associated with ET-1/Nox4 signal pathway in diabetic rats.
复制标题
argirein通过抑制与ET-1/Nox4信号通路相关的内皮细胞凋亡来改善糖尿病大鼠的血管功能障碍。
DOI：
10.1038/s41598-018-30386-w
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发表时间：
2018-08-22
影响因子：
4.6
通讯作者：
Xu M
中科院分区：
文献类型：
--
作者：
Su J;An XR;Li Q;Li XX;Cong XD;Xu M
内皮细胞凋亡在2型糖尿病（T2DM）血管并发症的病理生理机制中起重要作用。阿吉林，一种新的合成化合物被证明可以灭活NADPH氧化酶，以减轻2型糖尿病患者的心功能障碍。在这里，我们研究了argirin药物是否通过抑制与NADPH氧化酶相关的内皮细胞凋亡来减轻T2DM患者的血管功能障碍。将大鼠主动脉内皮细胞（RAECs）与葡萄糖（30 mM）体外培养48小时。结果表明，高糖显著提高raec中BAX （Bcl-2相关X蛋白）和Caspase-3蛋白的表达，降低Bcl2 （b细胞白血病/淋巴瘤2）蛋白的表达，并通过argiin药物使其正常化。精氨酸可显著抑制膜联蛋白V-FITC结合细胞百分比和琼脂糖电泳DNA片段，证实精氨酸在raec中的抗凋亡作用。此外，我们发现精氨酸阻断了内皮素(ET)-1/Nox4信号依赖性超氧化物（O2−.）的产生，而这一信号依赖性超氧化物（O2−.）调节raec中内皮细胞的凋亡。在体内，精氨酸干预可缓解高脂饲料（HFD）大鼠注射链脲佐菌素（STZ）后对乙酰胆碱的血管舒张反应，恢复主动脉内皮中Nox4和BAX的表达。我们首次证明了argirein可以抑制血管内皮细胞凋亡，这是由于阻断了raec中ET-1/Nox4信号依赖性的O2−生成。本研究揭示了精豆素通过抑制内皮细胞凋亡来预防T2DM血管并发症的治疗作用，这与精豆素的抗氧化特性有关。
Endothelial cell apoptosis plays an important role in the pathophysiological mechanism of vascular complications in type 2 diabetes mellitus (T2DM). Argirein, a new synthetic compound was demonstrated to inactivate NADPH oxidase to alleviate cardiac dysfunction in T2DM. Here, we investigated whether argirein medication attenuated the vascular dysfunction in T2DM by inhibiting endothelial cell apoptosis which was associated with NADPH oxidase. The rat aortic endothelial cells (RAECs) were incubated with glucose (30 mM) for 48 hour in vitro. It was shown that high glucose significantly increased the protein expression of BAX (Bcl-2 Associated X protein) and Caspase-3 and decreased Bcl2 (B-Cell Leukemia/Lymphoma 2) protein level in RAECs, which was normalized by argirein medication. The annexin V-FITC bound cell percentage and DNA fragments in agarose electrophoresis were markedly suppressed by argirein to confirm the anti-apoptotic property of argirein in RAECs. Furthermore, we found that argirein blocked the endothelin (ET)-1/Nox4 signal-dependent superoxide (O2−.) generation, which regulated endothelial cell apoptosis in RAECs. In vivo, argirein intervention relieved the vasodilatory response to acetylcholine and restored the expressions of Nox4 and BAX in the aorta endothelium of high-fat diet (HFD)-fed rats following streptozocin (STZ) injection. For the first time, we demonstrated that argirein could inhibit vascular endothelial cell apoptosis, which was attributed to blocking ET-1/Nox4 signal-dependent O2− generation in RAECs. This current study revealed the therapeutic effects of argirein to prevent the vascular complication in T2DM through inhibiting endothelial cell apoptosis which was associated with the anti-oxidative property of argirein.
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DOI：
10.1073/pnas.1600511113
发表时间：
2016-02-23
影响因子：
11.1
作者：
Hathaway, Catherine K.;Chang, Albert S.;Kakoki, Masao
通讯作者：
Kakoki, Masao
DOI：
10.1111/j.1440-1681.2008.05055.x
发表时间：
2008-11-01
影响因子：
2.9
作者：
Selemidis, Stavros
通讯作者：
Selemidis, Stavros
糖尿病心脏内质网应激和细胞凋亡引起的钙处理蛋白抑制可被阿甘油减弱
影响因子：
3.6
作者：
Shi, F. H.;Cheng, Y. S.;Dai, Y.
通讯作者：
Dai, Y.
内皮素 1 激活内皮素 A 受体/NADPH 氧化酶途径和减少的抗氧化剂对盐敏感性高血压中的内皮祖细胞减少和功能障碍有重要影响
DOI：
10.1161/hypertensionaha.111.183368
发表时间：
2012-05
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Chen DD;Dong YG;Yuan H;Chen AF
通讯作者：
Chen AF
影响因子：
2.4
作者：
Prakash, Kiran;Chandran, Dinu S.;Deepak, Kishore K.
通讯作者：
Deepak, Kishore K.