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Interferon-γ and high glucose-induced opening of Cx43 hemichannels causes endothelial cell dysfunction and damage.
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2020-04-14 , DOI: 10.1016/j.bbamcr.2020.118720
Juan C Sáez 1 , Susana Contreras-Duarte 2 , Valeria C Labra 3 , Cristian A Santibañez 3 , Luis A Mellado 3 , Carla A Inostroza 3 , Tanhia F Alvear 3 , Mauricio A Retamal 4 , Victoria Velarde 5 , Juan A Orellana 3
Affiliation  

Both IFN-γ or high glucose have been linked to systemic inflammatory imbalance with serious repercussions not only for endothelial function but also for the formation of the atherosclerotic plaque. Although the uncontrolled opening of connexin hemichannels underpins the progression of various diseases, whether they are implicated in endothelial cell dysfunction and damage evoked by IFN-γ plus high glucose remains to be fully elucidated. In this study, by using live cell imaging and biochemical approaches, we demonstrate that IFN-γ plus high glucose augment endothelial connexin43 hemichannel activity, resulting in the increase of ATP release, ATP-mediated Ca2+ dynamics and production of nitric oxide and superoxide anion, as well as impaired insulin-mediated uptake and intercellular diffusion of glucose and cell survival. Based on our results, we propose that connexin 43 hemichannel inhibition could serve as a new approach for tackling the activation of detrimental signaling resulting in endothelial cell dysfunction and death caused by inflammatory mediators during atherosclerosis secondary to diabetes mellitus.

中文翻译:

干扰素-γ和高葡萄糖诱导的Cx43半通道的开放导致内皮细胞功能障碍和损害。

IFN-γ或高葡萄糖都与全身性炎症失衡有关,不仅对内皮功能而且对动脉粥样硬化斑块的形成都有严重影响。尽管连接蛋白半通道的不受控制的开放支持了各种疾病的进展,但是它们是否与内皮细胞功能障碍和IFN-γ加高葡萄糖引起的损害有关,仍有待充分阐明。在这项研究中,通过使用活细胞成像和生化方法,我们证明了IFN-γ加高葡萄糖可增加内皮连接蛋白43半通道活性,从而导致ATP释放增加,ATP介导的Ca2 +动力学增加以及一氧化氮和超氧阴离子的产生,以及胰岛素介导的摄取和葡萄糖在细胞内的扩散以及细胞存活的受损。根据我们的结果,
更新日期:2020-04-20
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