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首页> 美国卫生研究院文献>Molecules >Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria
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Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria

机译：商业氨基糖苷类抑制细菌表达的人类连接蛋白半通道。

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摘要

In addition to gap junctional channels that mediate cell-to-cell communication, connexins form hemichannels that are present at the plasma membrane. Since hemichannels are permeable to small hydrophilic compounds, including metabolites and signaling molecules, their abnormal opening can cause or contribute to cell damage in disorders such as cardiac infarct, stroke, deafness, skin diseases, and cataracts. Therefore, hemichannels are potential pharmacological targets. A few aminoglycosides, well-known broad-spectrum antibiotics, have been shown to inhibit hemichannels. Here, we tested several commercially available aminoglycosides for inhibition of human connexin hemichannels using a cell-based bacterial growth complementation assay that we developed recently. We found that kanamycin A, kanamycin B, geneticin, neomycin, and paromomycin are effective inhibitors of hemichannels formed by connexins 26, 43, and 46 (Cx26, Cx43, and Cx46). Because of the >70 years of clinical experience with aminoglycosides and the fact that several of the aminoglycosides tested here have been used in humans, they are promising starting points for the development of effective connexin hemichannel inhibitors.
机译：除了介导细胞间通讯的间隙连接通道外，连接蛋白还形成存在于质膜上的半通道。由于半通道可渗透小的亲水性化合物（包括代谢物和信号分子），因此它们的异常开放会导致或导致诸如心梗，中风，耳聋，皮肤病和白内障等疾病的细胞损伤。因此，半通道是潜在的药理靶标。一些氨基糖苷类，众所周知的广谱抗生素，已显示出抑制半通道的作用。在这里，我们使用了我们最近开发的基于细胞的细菌生长互补测定法，测试了几种可商购的氨基糖苷类化合物对人连接蛋白半通道的抑制作用。我们发现卡那霉素A，卡那霉素B，遗传霉素，新霉素和巴龙霉素是由连接蛋白26、43和46（Cx26，Cx43和Cx46）形成的半通道的有效抑制剂。由于在氨基糖苷方面已有70多年的临床经验，而且这里所测试的几种氨基糖苷已在人体中使用，因此它们是开发有效的连接蛋白半通道抑制剂的有希望的起点。

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