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Selective Inhibition of PKC theta Protects Murine Hearts against Ischemia/Reperfusion Injury: Cross‐talk with T Lymphocytes
Author(s) -
Li Zhao,
Abdullah Chowdhury S.,
Jin ZhuQiu
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.652.4
Subject(s) - knockout mouse , ischemia , reperfusion injury , cardioprotection , protein kinase c , chemistry , creatine kinase , phosphorylation , medicine , endocrinology , pharmacology , biochemistry , receptor
PKC theta is vital for activation of mature T lymphocytes. Infiltration of T cells in myocardial tissue has been observed in patients with coronary heart disease. The mechanistic role of T cells in heart injury remains elusive. In this study, effect of deactivation of mature T cells on myocardial ischemia/reperfusion (IR) injury was elucidated with two approaches: Pharmacological inhibition with a selective PKC theta inhibitor (PKCI) and genetic manipulation with Rag 1 knockout mice. Male C57BL/6J mice and Rag1 knockout mice (20 ~ 25 g) were anesthetized. Langendorff hearts perfused with Krebs‐Henseleit were prepared. Hemodynamic parameters were recorded. Creatine kinase (CK) and infarct size were measured. T cells counting, phosphorylation of PKC theta at T538 and PKC theta translocation were determined. Pretreatment with PKCI at 1 microM or 100 nM protected hearts against 50 min of global ischemia and 50 min of reperfusion as evidenced by low CK release and decreased infarct size in C57BL/6J hearts. PKCI reduced the expression of phosphorylation of PKC theta and PKC theta translocation. Myocardial IR injury was attenuated in Rag1 knockout mice, denoted by small portion of infarct size and low CK release. PKCI‐induced cardioprotection was abrogated in Rag1 knockout mice. The present results reveal that deactivation of mature T cells protects hearts against ischemia and reperfusion injury.