Protein kinase C-Fyn kinase cascade mediates the oleic acid-induced disassembly of neonatal rat cardiomyocyte adherens junctions.

Abstract

Oleic acid (OA) affects assembly of gap junctions in neonatal cardiomyocytes. Adherens junction (AJ) regulates the stability of gap junction integrity; however, the effect of OA on AJ remains largely unexplored. The distribution of N-cadherin and catenins at cell-cell junction was decreased by OA. OA induced activation of protein kinase C(PKC)-alpha and -epsilon and Src family kinase, and all three kinases were involved in the oleic acid-induced disassembly of the adherens junction, since it was blocked by pretreatment with Gö6976 (a PKCalpha inhibitor), epsilonV1-2 (a PKCepsilon inhibitor), or PP2 (a Src family kinase inhibitor). Src family kinase appeared to be the downstream of PKC-alpha and -epsilon, as blockade of either PKC-alpha or -epsilon activity prevented the OA-induced activation of Src family kinase. Immunoprecipitation analyses showed that OA activated Fyn and Fer. OA promoted the association of p120 catenin/beta-catenin with Fyn and Fer and caused increased tyrosine phosphorylation of p120 catenin and beta-catenin, resulting in decreased binding of the former to N-cadherin and of the latter to alpha-catenin. Pretreatment with PP2 abrogated this OA-induced tyrosine phosphorylation of p120 catenin and beta-catenin and restored the association of N-cadherin with p120 catenin and that of beta-catenin with alpha-catenin. In conclusion, these results show that OA activates the PKC-Fyn signaling pathway, leading to the disassembly of the AJ. Therefore, inhibitors of PKC-alpha/-epsilon and Src family kinase are potential candidates as cardioprotection agents against OA-induced heart injury during ischemia-reperfusion.

• Authors: Kwan-Lih Hsu, Han-Jou Fan, Yung-Chia Chen, Yuahn-Sieh Huang, Chia-Huei Chen, Jiahn-Chun Wu, Seu-Mei Wang
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 41 Issue 7 Pg. 1536-46 (Jul 2009) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 19166962 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Catenins
• Cell Adhesion Molecules
• Phosphoproteins
• Protein Kinase Inhibitors
• beta Catenin
• Phosphotyrosine
• Oleic Acid
• Fyn protein, rat
• Proto-Oncogene Proteins c-fyn
• src-Family Kinases
• Protein Kinase C
• Protein Kinase C-alpha
• Protein Kinase C-epsilon
• Delta Catenin
• Ctnnd1 protein, rat

Topics

• Adherens Junctions (drug effects, enzymology)
• Animals
• Animals, Newborn
• Apoptosis (drug effects)
• Catenins
• Cell Adhesion Molecules (metabolism)
• Cells, Cultured
• Enzyme Activation (drug effects)
• Models, Biological
• Myocytes, Cardiac (cytology, drug effects, enzymology)
• Necrosis (enzymology)
• Oleic Acid (pharmacology)
• Phosphoproteins (metabolism)
• Phosphorylation (drug effects)
• Phosphotyrosine (metabolism)
• Protein Kinase C (antagonists & inhibitors, metabolism)
• Protein Kinase C-alpha (metabolism)
• Protein Kinase C-epsilon (metabolism)
• Protein Kinase Inhibitors (pharmacology)
• Proto-Oncogene Proteins c-fyn (metabolism)
• Rats
• Rats, Wistar
• beta Catenin (metabolism)
• src-Family Kinases (metabolism)
• Delta Catenin