Cholesterol modulates function of connexin 43 gap junction channel via PKC pathway in H9c2 cells.

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  • Additional Information
    • Source:
      Publisher: Elsevier Pub. Co Country of Publication: Netherlands NLM ID: 0217513 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0006-3002 (Print) Linking ISSN: 00063002 NLM ISO Abbreviation: Biochim Biophys Acta Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam : Elsevier Pub. Co.
    • Subject Terms:
      Cholesterol/*pharmacology ; Connexin 43/*metabolism ; Gap Junctions/*drug effects ; Heart/*drug effects ; Protein Kinase C/*metabolism ; Signal Transduction/*drug effects; Animals ; Apoptosis/drug effects ; Blotting, Western ; Cell Communication/drug effects ; Cell Proliferation/drug effects ; Cells, Cultured ; Enzyme Inhibitors/pharmacology ; Fluorescent Antibody Technique ; Phosphorylation/drug effects ; Protein Kinase C/antagonists & inhibitors ; Rats
    • Abstract:
      It has been shown that cholesterol modulates activity of protein kinase C (PKC), and PKC phosphorylates connexin 43 (Cx43) to regulate its function, respectively. However, it is not known whether cholesterol modulates function of Cx43 through regulating activity of PKC. In the present study, we demonstrated that cholesterol enrichment reduced the dye transfer ability of Cx43 in cultured H9c2 cells. Western blot analysis indicated that cholesterol enrichment enhanced the phosphorylated state of Cx43. Immunofluorescent images showed that cholesterol enrichment made the Cx43 distribution from condensed to diffused manner in the interface between the cells. In cholesterol enriched cells, PKC antagonists partially restored the dye transfer ability among the cells, downregulated the phosphorylation of Cx43 and redistributed Cx43 from the diffused manner to the condensed manner in the cell interface. In addition, reduction of cholesterol level suppressed PKC activity to phosphorylate Cx43 and restored Cx43 function in PKC agonist-treated cells. Furthermore, we demonstrated that cholesterol enrichment upregulated the phosphorylated state of Cx43 at Ser368, while PKC antagonists reversed the effect. Taken together, cholesterol level in the cells plays important roles in regulating Cx43 function through activation of the PKC signaling pathway.
      (Copyright © 2014 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: Cholesterol depletion; Cholesterol enrichment; Cx43 phosphorylation; Dye transfer; Protein kinase C
    • Accession Number:
      0 (Connexin 43)
      0 (Enzyme Inhibitors)
      97C5T2UQ7J (Cholesterol)
      EC 2.7.11.13 (Protein Kinase C)
    • Publication Date:
      Date Created: 20140501 Date Completed: 20140729 Latest Revision: 20161126
    • Publication Date:
      20240829
    • Accession Number:
      10.1016/j.bbamem.2014.04.016
    • Accession Number:
      24780378