Z. Li, Nicolas Chambron, Zhu-qiu Jin
Apr 1, 2011
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Journal
The FASEB Journal
Abstract
PKC theta (PKC θ), one of the novel PKC subfamily, plays a critical role in activation of T cells and infiltration of T cells has been observed in patients with coronary heart disease. The role of PKC θ in myocardial ischemia/reperfusion (IR) injury remains unknown. To this purpose, a cell‐permeable PKC θ inhibitor was used in a Langendorff IR model. Male C57BL/6J mouse hearts were perfused with Krebs‐Henseleit solution. Cardiac contractility was recorded with force transducer. Creatine kinase (CK) release in coronary effluent was measured. Mice were divided into four groups: Control, IR, PKC θ pseudosubstrate inhibitor (100 nM and 1 μM). Control hearts were perfused with K‐H buffer for 120 min. IR and PKC θ hearts were subjected to 50 min of global ischemia and 50 min of reperfusion after 20 min of equilibration. IR decreased cardiac contractile force and increased CK release. PKC θ inhibitor pretreatment groups were able to reduce CK release and minimize infarct size (% of Risk Area, 41.5 ± 15.0% in IR group, vs 6.7 ± 1.7% in PKC θ inhibitor 1 μM, and 11.1 ± 4.2% in 100 nM group, P<0.05, compared with IR group, n=3–5/per group). Translocation of PKC θ from cytosol to membrane and enhanced phosphorylation of PKC θ were observed in IR hearts. In conclusion, activation of PKC θ plays an important role in myocardial IR injury and inhibition of PKC θ can protect hearts from ischemia/reperfusion injury.