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Protein Kinase C epsilon (PKC ε+) peptide activator exerts cardioprotective effects in ischemia/reperfusion injury when given prior to ischemia
Author(s) -
Teng Jane Chunwen,
Adams Jovan S,
Kay Helen,
Grilli Christopher,
Guglielmello Giuseppe,
Bell Adrian,
Young Lindon H
Publication year - 2006
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.20.5.a1155-c
Subject(s) - protein kinase c , ischemia , medicine , nitric oxide , reperfusion injury , activator (genetics) , endocrinology , endothelial dysfunction , pharmacology , chemistry , kinase , biochemistry , receptor
Ischemia followed by reperfusion (I/R) in the presence of polymorphonuclear leukocytes (PMNs) results in cardiac contractile dysfunction. Enhancing endothelial nitric oxide (NO) release prior to ischemia attenuates cardiac contractile dysfunction following I/R. A cell‐permeable PKC ε peptide activator enhances NO release when given to rat aortic segments. We studied isolated rat hearts following ischemia (20 min) and reperfusion (45 min) in the presence of activated PMNs. In hearts given PKC ε+ (5 μM, n = 6) prior to I/R and reperfused with PMNs, left ventricular developed pressure (LVDP) and the maximal rate of LVDP (+dP/dt max ) recovered to 90% ± 10% and 89% ± 9% of baseline values, respectively, at 45 min post‐reperfusion, and these cardioprotective responses were blocked by N G ‐nitro‐L‐arginine methyl ester (L‐NAME). I/R hearts receiving PMNs alone (n = 10) recovered to 58% ± 4% and 49% ± 4% of baseline values for LVDP and +dP/dt max respectively. The effect of PKC ε+ on LVDP and +dP/dt max was significant (p<0.01) compared to I/R + PMN hearts at 45 min post‐reperfusion. The PKC ε+ significantly increased endothelial NO release (p<0.01) from a basal value of 2.12 ± 0.39 (n = 11) pmol NO/mg tissue to 4.76 ± 0.36 pmol NO/mg tissue for 5 μM (n = 36), and this response was blocked by L‐NAME. These results suggest that PKC ε+ attenuates PMN induced post‐I/R cardiac contractile dysfunction, in part, by increasing endothelial NO release prior to ischemia. This study was supported by NHLBI Grant 1R15HL‐76235‐01.