Signaling pathways involved in postconditioning-induced cardioprotection of human myocardium, in vitro.
We examined the respective role and relationship between protein kinase C (PKC), mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel and p38 mitogen-activated protein kinase (MAPK) in postconditioning of human myocardium, in vitro. Isometrically contracting, isolated human right atrial trabeculae were exposed to 30 min hypoxia and 60 min reoxygenation. Phorbol 12-myristate 13-acetate (a PKC activator), diazoxide (a mitoK(ATP) opener) and anisomycin (a p38 MAPK activator) were superfused in early reoxygenation alone and with calphostin C (a PKC inhibitor), 5-hydroxy-decanoate (5-HD, a mitoK(ATP) channel inhibitor) and SB 202190 (a p38 MAPK inhibitor). Developed force at the end of the 60 min reoxygenation (FoC(60)) period was compared between groups (mean +/- SD). Phorbol 12-myristate 13-acetate (91 +/- 4% of baseline), diazoxide (85 +/- 5% of baseline) and anisomycin (90 +/- 4% of baseline) enhanced the FoC(60) as compared with the control group (53 +/- 7% of baseline, P < 0.0001). The enhanced FoC(60) induced by phorbol 12-myristate 13-acetate was abolished by calphostin C (52 +/- 5% of baseline) and 5-HD (56 +/- 3% of baseline), but not by SB 202190 (90 +/- 8%). The diazoxide-induced recovery of FoC(60) was attenuated by 5-HD (55 +/- 6% of baseline), but was not modified by calphostin C (87 +/- 5% of baseline) and SB 202190 (90 +/- 8% of baseline). The anisomycin-induced recovery of FoC(60) was abolished by calphostin C (61 +/- 9% of baseline) and SB 202190 (52 +/- 8% of baseline), but not by 5-HD (88 +/- 6% of baseline). In conclusion, PKC activation, opening of mitoK(ATP) channels and p38 MAPK activation in early reoxygenation induced the postconditioning of human myocardium, in vitro. Furthermore, PKC activation was upstream of the opening of mitoK(ATP) channels; p38 MAPK acted on PKC. Therefore, mitoK(ATP) and p38 MAPK seemed to be involved in two independent pathways.
Laboratory of Experimental Anesthesiology and Cellular Physiology EA3212, Institut Fédératif de Recherche ICORE146 Université de Caen Basse Normandie, CHU de Caen, 14033 Caen Cedex, France. sand.lemoine2@wanadoo.fr
Sandrine
S
Lemoine
Paolo Emilio
PE
Puddu
Charline
C
Durand
Olivier
O
Lepage
Gérard
G
Babatasi
Calin
C
Ivascau
Massimo
M
Massetti
Jean-Louis
JL
Gérard
Jean-Luc
JL
Hanouz
D006321:Heart / Q000502:physiology*; D006801:Humans; D053580:Muscle Strength; D010809:Physical Fitness / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D011493:Protein Kinase C; D048051:p38 Mitogen-Activated Protein Kinases