論文

査読有り 国際誌
2016年10月

Connexin43 hemichannels contributes to the disassembly of cell junctions through modulation of intracellular oxidative status.

Redox biology
  • Yuan Chi
  • ,
  • Xiling Zhang
  • ,
  • Zhen Zhang
  • ,
  • Takahiko Mitsui
  • ,
  • Manabu Kamiyama
  • ,
  • Masayuki Takeda
  • ,
  • Jian Yao

9
開始ページ
198
終了ページ
209
記述言語
英語
掲載種別
DOI
10.1016/j.redox.2016.08.008

Connexin (Cx) hemichannels regulate many cellular processes with little information available regarding their mechanisms. Given that many pathological factors that activate hemichannels also disrupts the integrity of cellular junctions, we speculated a potential participation of hemichannels in the regulation of cell junctions. Here we tested this hypothesis. Exposure of renal tubular epithelial cells to Ca2+-free medium led to disassembly of tight and adherens junctions, as indicated by the reduced level of ZO-1 and cadherin, disorganization of F-actin, and severe drop in transepithelial electric resistance. These changes were preceded by an activation of Cx43 hemichannels, as revealed by extracellular efflux of ATP and intracellular influx of Lucifer Yellow. Inhibition of hemichannels with chemical inhibitors or Cx43 siRNA greatly attenuated the disassembly of cell junctions. Further analysis using fetal fibroblasts derived from Cx43 wide-type (Cx43+/+), heterozygous (Cx43+/-) and knockout (Cx43-/-) littermates showed that Cx43-positive cells (Cx43+/+) exhibited more dramatic changes in cell shape, F-actin, and cadherin in response to Ca2+ depletion, as compared to Cx43-null cells (Cx43-/-). Consistently, these cells had higher level of protein carbonyl modification and phosphorylation, and much stronger activation of P38 and JNK. Hemichannel opening led to extracellular loss of the major antioxidant glutathione (GSH). Supplement of cells with exogenous GSH or inhibition of oxidative sensitive kinases largely prevented the above-mentioned changes. Taken together, our study indicates that Cx43 hemichannels promote the disassembly of cell junctions through regulation of intracellular oxidative status.

リンク情報
DOI
https://doi.org/10.1016/j.redox.2016.08.008
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/27567473
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5007435
ID情報
  • DOI : 10.1016/j.redox.2016.08.008
  • PubMed ID : 27567473
  • PubMed Central 記事ID : PMC5007435

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