Opening of mitochondrial K(ATP) channel occurs downstream of PKC-epsilon activation in the mechanism of preconditioning.
We examined whether the mitochondrial ATP-sensitive K channel (K(ATP)) is an effector downstream of protein kinase C-epsilon (PKC-epsilon) in the mechanism of preconditioning (PC) in isolated rabbit hearts. PC with two cycles of 5-min ischemia/5-min reperfusion before 30-min global ischemia reduced infarction from 50.3 +/- 6.8% of the left ventricle to 20.3 +/- 3.7%. PC significantly increased PKC-epsilon protein in the particulate fraction from 51 +/- 4% of the total to 60 +/- 4%, whereas no translocation was observed for PKC-delta and PKC-alpha. In mitochondria separated from the other particulate fractions, PC increased the PKC-epsilon level by 50%. Infusion of 5-hydroxydecanoate (5-HD), a mitochondrial K(ATP) blocker, after PC abolished the cardioprotection of PC, whereas PKC-epsilon translocation by PC was not interfered with 5-HD. Diazoxide, a mitochondrial K(ATP) opener, infused 10 min before ischemia limited infarct size to 5.2 +/- 1.4%, but this agent neither translocated PKC-epsilon by itself nor accelerated PKC-epsilon translocation after ischemia. Together with the results of earlier studies showing mitochondrial K(ATP) opening by PKC, the present results suggest that mitochondrial K(ATP)-mediated cardioprotection occurs subsequent to PKC-epsilon activation by PC.
Ohnuma
Yoshito
Y
Second Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
Miura
Tetsuji
T
Miki
Takayuki
T
Tanno
Masaya
M
Kuno
Atsushi
A
Tsuchida
Akihito
A
Shimamoto
Kazuaki
K
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology; D003981:Diazoxide / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics; D006880:Hydroxy Acids / Q000494:pharmacology; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D017202:Myocardial Ischemia / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D011817:Rabbits; D013347:Subcellular Fractions / Q000737:chemistry; D014665:Vasodilator Agents / Q000494:pharmacology
D003652:Decanoic Acids; D006880:Hydroxy Acids; D007527:Isoenzymes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014665:Vasodilator Agents; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D003981:Diazoxide