Mechanism of oleic acid-induced gap junctional disassembly in rat cardiomyocytes

Yuahn Sieh Huang, Yung Zu Tseng, Jiahn Chun Wu, Seu Mei Wang*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


This study investigated the mechanism of oleic acid (OA) on gap junctions and identified the protein kinase C (PKC) isoforms involved in OA-mediated gap junction disassembly in cardiomyocytes. Control cardiomyocytes showed continuous staining of the plasma membrane at cell-cell contact areas using antibodies reacting with connexin 43 (Cx43). The spontaneous contraction rate of cultured cardiomyocytes was reduced in a time-dependent manner by OA. In addition, Cx43 expression at cell-cell junction decreased, suggesting the disassembly of gap junction. Staining for PKCε and PKCα, which were shown to colocalize with Cx43, also decreased with increased duration of OA treatment. The effects of OA on these distributional changes at cell junctions were reversed by 24 h incubation in fresh culture medium devoid of OA. Immunoprecipitation assays confirmed the biochemical binding between Cx43 and PKCε/PKCα, and this protein interaction was not affected by OA. This may provide the basis for simultaneous detachment of Cx and PKCε/PKCα from the cell-cell junction to the cytosol upon OA stimulation. Western blot analysis showed that OA-induced Cx43 Ser368 phosphorylation, and that this effect could be blocked by cotreatment with the general PKC inhibitor, calphostin C, the PKCε inhibitor, eV1-2, or the Src kinase inhibitor, PP1, but not by the PKCα inhibitor, Gö6976. eV1-2 also prevented the OA-induced disassembly of gap junctions. Taken together, these data suggest that OA-induced Cx43 Ser368 phosphorylation is mediated by activation of PKCε and Src kinase and might be responsible for OA-induced gap junctional disassembly.

Original languageEnglish
Pages (from-to)755-766
Number of pages12
JournalJournal of Molecular and Cellular Cardiology
Issue number3
StatePublished - Sep 2004


  • Cardiomyocyte
  • Connexin43
  • Gap junction disassembly
  • PKCε
  • Serine368 phosphorylation


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