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The mechanisms related to the cardioprotective effects of protein kinase C epsilon (PKC ε‐) peptide inhibitor in ischemia/reperfusion (I/R) injury when given at reperfusion
Author(s) -
Chen Qian,
Kay Helen Young,
Teng Jane,
Burkhart Samantha,
Zambrano Christopher,
Krass Samuel,
Adams Jovan,
Grilli Christopher,
Guglielmello Giuseppe,
Brue Richard,
Young Lindon Howard
Publication year - 2008
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.22.1_supplement.730.27
Subject(s) - reperfusion injury , protein kinase c , cardioprotection , myeloperoxidase , chemistry , infiltration (hvac) , pharmacology , ischemia , medicine , inflammation , biochemistry , kinase , physics , thermodynamics
PKC is a key enzyme involved in I/R injury. Previously, we showed that PKC ε− significantly restored postreperfused cardiac function up to 99% in polymorphonuclear leukocytes (PMNs, 200×10 6 ) induced myocardial I/R injury rat model. In this study, we further investigated the effect of PKC ε− on cardiac I/R injury and the underlying mechanisms. Compared to I/R+PMN hearts, we found that PKC ε− treated I/R+PMN hearts exhibited less cell injury and significantly lower PMN vascular adherence/infiltration in 45 min posterperfused heart tissue by using triphenyltetrazolium chloride staining, hemoxylin & eosin stain and myeloperoxidase assay. Furthermore, expression of endothelial adhesion molecules (i.e., intercellular adhesion molecule‐1; ICAM‐1) which contributes to PMN adherence/infiltration was also significantly decreased by 47±5% (P<0.05). Moreover, the NOS inhibitor, N G ‐nitro‐L‐arginine methyl ester, did not block the cardioprotection of PKC ε−. However, PKC ε− (0.4 mg/Kg) significantly decreased hydrogen peroxide release during reperfusion in an in vivo femoral I/R model. Therefore, cardioprotection of PKC ε− is possibly related to attenuating ICAM‐1 expression, PMN adherence/infiltration and oxidative stress during reperfusion. This study was supported by NHLBI Grant 1R15HL‐76235‐01 and Center For Chronic Disorders Of Aging at PCOM.