2013年
Connexin43 hemichannel-mediated regulation of connexin43.
PloS one
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- 巻
- 8
- 号
- 2
- 開始ページ
- e58057
- 終了ページ
- 記述言語
- 英語
- 掲載種別
- DOI
- 10.1371/journal.pone.0058057
BACKGROUND: Many signaling molecules and pathways that regulate gap junctions (GJs) protein expression and function are, in fact, also controlled by GJs. We, therefore, speculated an existence of the GJ channel-mediated self-regulation of GJs. Using a cell culture model in which nonjunctional connexin43 (Cx43) hemichannels were activated by cadmium (Cd(2+)), we tested this hypothesis. PRINCIPAL FINDINGS: Incubation of Cx43-transfected LLC-PK1 cells with Cd(2+) led to an increased expression of Cx43. This effect of Cd(2+) was tightly associated with JNK activation. Inhibition of JNK abolished the elevation of Cx43. Further analysis revealed that the changes of JNK and Cx43 were controlled by GSH. Supplement of a membrane-permeable GSH analogue GSH ethyl ester or GSH precursor N-acetyl-cystein abrogated the effects of Cd(2+) on JNK activation and Cx43 expression. Indeed, Cd(2+) induced extracellular release of GSH. Blockade of Cx43 hemichannels with heptanol or Cx43 mimetic peptide Gap26 to prevent the efflux of GSH significantly attenuated the Cx43-elevating effects of Cd(2+). CONCLUSIONS: Collectively, our results thus indicate that Cd(2+)-induced upregulation of Cx43 is through activation of nonjunctional Cx43 hemichannels. Our findings thus support the existence of a hemichannel-mediated self-regulation of Cx43 and provide novel insights into the molecular mechanisms of Cx43 expression and function.
- リンク情報
- ID情報
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- DOI : 10.1371/journal.pone.0058057
- PubMed ID : 23460926
- PubMed Central 記事ID : PMC3584027