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PKC delta Peptide Activator exerts anti-inflammation and cardio-protective effects

Qian Chen

Abstract


Ischemia followed by reperfusion (I/R) causes additional cell injury.  Reperfusion injury is initiated by vascular endothelial dysfunction and/or oxidative stress, which is further augmented by leukocytes (i.e., polymorphonuclear leukocyte [PMN]) activation and recruitment.  Protein kinase C (PKC) is a key signaling molecule mediating reperfusion injury.  The role of PKC delta (d) isoform in myocardial I/R injury is still being debated.  In this study, we tested the effects of PKC d peptide activator (PKC d+) on inflammation and PMN-induced postreperfused cardiac function.  We found that PKC d+ significantly reduced phorbol-12-myristate-13-acetate (PMA, 15 nM)-induced superoxide (SO) release in isolated rat PMNs. Furthermore, PKC d+ (5 and 10 mM, both n = 5) dose-dependently decreased NG-nitro-L-arginine methyl ester (L-NAME)-induced leukocyte-endothelial interactions in rat mesenteric microcirculation in vivo by intravital microscopy. Lastly, we tested the effects of PKC d+ on I/R+PMNs-induced postreperfused cardiac dysfunction in isolated perfused rat hearts.  We found that PKC d+ (10 mM, n = 6) significantly attenuated PMN-induced cardiac dysfunction as compared with control I/R+PMNs hearts (n = 10) in left ventricular developed pressure (LVDP), end diastolic pressure (EDP), and the maximal rate of LVDP (+dP/dtmax; all P<0.05).  We also found that PKC d+ treated postreperfused heart tissue showed significantly lower leukocyte vascular adherence and tissue infiltration. These results suggest that PKC d+ attenuated PMN-induced post I/R cardiac contractile and diastolic dysfunction, possibly by inhibiting leukocyte-endothelial interactions and attenuating PMN SO release.


Keywords


Ischemia/reperfusion injury, PKC delta isoform, Superoxide, Leukocyte-endothelial interactions, Cardiac function

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References


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DOI: http://dx.doi.org/10.18103/mra.v0i2.62

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