Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria.
Inhibition by Commercial Aminoglycosides of Human Connexin Hemichannels Expressed in Bacteria.
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DOI：
10.3390/molecules22122063
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发表时间：
2017-11-25
期刊：
影响因子：
--
通讯作者：
Altenberg GA
中科院分区：
文献类型：
--
作者：
Fiori MC;Krishnan S;Kjellgren A;Cuello LG;Altenberg GA
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。由于半通道对于小的亲水性化合物（包括代谢物和信号传导分子）是可渗透的，因此它们的异常打开可导致或促成诸如心肌梗塞、中风、耳聋、皮肤病和白内障的病症中的细胞损伤。因此，半通道是潜在的药理学靶点。一些氨基糖苷类，众所周知的广谱抗生素，已被证明可以抑制半通道。在这里，我们测试了几种市售的氨基糖苷类抑制人类连接蛋白半通道使用细胞为基础的细菌生长互补试验，我们最近开发的。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。由于氨基糖苷类药物有超过70年的临床经验，并且这里测试的几种氨基糖苷类药物已用于人类，因此它们是开发有效连接蛋白半通道抑制剂的有希望的起点。
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.
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影响因子：
4
作者：
Fiori MC;Reuss L;Cuello LG;Altenberg GA
通讯作者：
Altenberg GA
DOI：
10.1152/ajpheart.00022.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Shintani-Ishida, Kaori;Uemura, Koichi;Yoshida, Ken-Ichi
通讯作者：
Yoshida, Ken-Ichi
影响因子：
3.1
作者：
Krishnan, Srinivasan;Fiori, Mariana C.;Cuello, Luis G.
通讯作者：
Cuello, Luis G.
影响因子：
4
作者：
Beyer EC;Berthoud VM
通讯作者：
Berthoud VM
影响因子：
3.7
作者：
Paulis LE;Klein AM;Ghanem A;Geelen T;Coolen BF;Breitbach M;Zimmermann K;Nicolay K;Fleischmann BK;Roell W;Strijkers GJ
通讯作者：
Strijkers GJ