Adenosine Triggers the Nuclear Translocation of Protein Kinase C Epsilon in H9c2 Cardiomyoblasts With the Loss of Phosphorylation at Ser729

作者：Xu Tian Rui; He Guiyuan; Rum**y Martin G^*

来源：Journal of Cellular Biochemistry, 2009, 106(4): 633-642.

DOI：10.1002/jcb.22043

• ADENOSINE
• H9c2 CARDIOMYOBLASTS
• NUCLEAR TRANSLOCATION
• PROTEIN KINASE C epsilon
• Ser729 PHOSPHORYLATION

Adenosine is a major mediator of ischaemic preconditioning (IPC) and cardioprotection. The translocation and activation of protein kinase C epsilon, triggered by adenosine, are essential for these processes. We report. here that H9c2 cardiomyoblasts express five PKC isoforms (alpha, beta(1), delta, epsilon and zeta). PKC epsilon is predominantly associated with F-actin fibres in unstimulated H9c2 cells but translocates to the nucleus on stimulation with adenosine. Cytosolic PKC epsilon associated with F-actin fibres is phosphorylated at Ser729 but nuclear PKC epsilon lacks phosphorylation at this site. Adenosine triggers the nuclear translocation after 5 min stimulation. PKC epsilon Ser729Ala and Ser729Glu mutants showed no translocation on adenosine stimulation suggesting both phosphorylation and serine at 729 are critical for this translocation. Among five PKC isoforms (alpha, beta(1), delta, epsilon and zeta) detected, PKC epsilon is the only isoform translocating to the nucleus upon adenosine stimulation. Disruption or microtubules (MTs), but not, F-actin-rich fibres, blocked translocation of both endogenous PKC epsilon and overexpressed GFP-PKC epsilon. to the nucleus. Ten proteins interacted with cytosolic PKC epsilon; five of which are components of myofibrils. Matrin 3 and vimentin interacted with nuclear PKC epsilon. These findings suggest that adenosine stimulates PKC epsilon, translocation to the nucleus in 119c2 cells in a mechanism involving dephosphorylation at Ser729 and MT, which should advance our understanding of the signalling pathways stimulated by adenosine in IPC and cardioprotection. J. Cell. Biochem. 106: 633-642, 2009.

• 出版日期2009-3-1