Preconditioning protects ischemic rabbit heart by protein kinase C activation

1994 ◽  
Vol 266 (3) ◽  
pp. H1145-H1152 ◽  
Author(s):  
K. Ytrehus ◽  
Y. Liu ◽  
J. M. Downey
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Isolated Heart ◽  
Polymyxin B ◽  
Rabbit Heart ◽  
Risk Zone ◽  
Kinase C ◽  
Regional Myocardial Ischemia

Myocardial protection in the rabbit induced by ischemic preconditioning is thought to be adenosine receptor linked, but the signaling pathway responsible for the protection has yet to be identified. This study tests whether protein kinase C could be involved. Either of two inhibitors of protein kinase C, staurosporine (50 micrograms/kg) or polymyxin B (24 mg/kg), were administered to rabbits subjected to 30 min regional myocardial ischemia followed by 180 min reperfusion. Half of the rabbits were preconditioned while the other half served as nonpreconditioned controls. Nonpreconditioned hearts without drug or treated with staurosporine or polymyxin B resulted in 37.8 +/- 3.1, 40.5 +/- 2.8, and 42.0 +/- 7.0% infarction of the risk zone, respectively. Preconditioning limited infarct size to 7.3 +/- 2.7%. Both inhibitors blocked protection in preconditioned hearts with 36.2 +/- 2.7 and 40.9 +/- 2.5% of the risk zone infarcted, respectively. Activation of protein kinase C with 4 beta-phorbol 12-myristate 13-acetate (PMA) or with 1-oleyl-2-acetyl glycerol (OAG) mimicked preconditioning in buffer-perfused hearts. PMA (0.01 nmol/min) or OAG (10 nmol/min) for 5 min was followed by 10 min of washout. Infarct size after 30 min regional ischemia was limited in the PMA and OAG groups (6.4 +/- 1.4 and 11.7 +/- 3.3 vs. 28.0 +/- 4.5% in untreated controls) and was equipotent with ischemic preconditioning (11.8 +/- 2.2%). Polymyxin B also blocked protection from ischemic preconditioning in the isolated heart (33.0 +/- 5.0%).(ABSTRACT TRUNCATED AT 250 WORDS)

Roles of Tyrosine Kinase and Protein Kinase C in Infarct Size Limitation by Repetitive Ischemic Preconditioning in the Rat

2000 ◽  
Vol 35 (3) ◽  
pp. 345-352 ◽  
Author(s):  
Masaya Tanno ◽  
Akihito Tsuchida ◽  
Yukinaga Nozawa ◽  
Tomoaki Matsumoto ◽  
Tohru Hasegawa ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Tyrosine Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Kinase C ◽  
Size Limitation ◽  
Infarct Size Limitation

Participation of protein kinase C in the activation of Nrf2 signaling by ischemic preconditioning in the isolated rabbit heart

2012 ◽  
Vol 372 (1-2) ◽  
pp. 169-179 ◽  
Author(s):  
Xin Zhang ◽  
Zhibin Xiao ◽  
Jianmin Yao ◽  
Genshang Zhao ◽  
Xianen Fa ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
Rabbit Heart ◽  
Isolated Rabbit Heart ◽  
Kinase C

Remifentanil Preconditioning Confers Cardioprotection via  Cardiac κ- and δ-Opioid Receptors

2005 ◽  
Vol 102 (2) ◽  
pp. 371-378 ◽  
Author(s):  
Ye Zhang ◽  
Michael G. Irwin ◽  
Tak Ming Wong ◽  
Mai Chen ◽  
Chun-Mei Cao
Keyword(s):  
At Risk ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Katp Channel ◽  
Area At Risk ◽  
Mitochondrial Katp Channel ◽  
Ringer’S Solution ◽  
Kinase C

Background Remifentanil preconditioning (RPC) reduces the infarct size in anesthetized rat hearts, and this effect seems to be mediated by all three types of opioid receptors (ORs). Because there is evidence of only kappa- and delta- but not mu-ORs in the rat heart, the authors investigated whether RPC confers cardioprotection via cardiac kappa- and delta-OR as well as via extracardiac mu-OR agonist activity. The authors also investigated the involvement of signaling mechanisms, namely protein kinase C and mitochondrial adenosine triphosphate-sensitive potassium (KATP) channels. Methods The hearts of male Sprague-Dawley rats weighing 190-210 g were removed, mounted on a Langendorff apparatus, and perfused retrogradely at 100 cm H2O with Krebs-Ringer's solution. All hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The study consisted of three series of experiments on the effect of ischemic preconditioning or RPC (10, 50, and 100 ng/ml remifentanil) after blockade of OR subtypes (delta-OR antagonist naltrindol, kappa-OR antagonist nor-binaltorphimine, and mu-OR antagonist CTOP). The involvement of protein kinase C or the KATP channel in the cardioprotection of RPC was also investigated using specific blockers in each group. RPC was produced by three cycles of 5-min perfusion of remifentanil in Krebs-Ringer's solution interspersed with a 5-min reperfusion with Krebs solution only. Infarct size, as a percentage of the area at risk, was determined by 2,3,5-triphenyltetrazolium staining. Results Infarct size as a percentage of the area at risk was significantly reduced after RPC from 51.9 +/- 5.0% (control, n = 8) to 36.2 +/- 10.0% (100 ng/ml RPC, n = 8, P < 0.01). This effect was stopped by pretreatment with naltrindol (52.3 +/- 5.2%) and nor-binaltorphimine (43.5 +/- 6.0%) but not CTOP (37.1 +/- 6.0%). Chelerythrine and GF109203X, both protein kinase C inhibitors, abolished the effects of RPC or ischemic preconditioning on infarct size as a percentage of area at risk. 5-Hydroxydecanoate (a selective mitochondrial KATP channel blocker) also abolished the cardioprotection of RPC and IPC, but HMR-1098 (a selective inhibitor of the sarcolemmal KATP channel) did not. Conclusion Cardiac delta- and kappa- but not mu-ORs mediate the cardioprotection produced by RPC. Both protein kinase C and the mitochondrial KATP channel were involved in this effect.

Stretch-induced protection shares a common mechanism with ischemic preconditioning in rabbit heart

1998 ◽  
Vol 274 (3) ◽  
pp. H955-H964 ◽  
Author(s):  
A. Gysembergh ◽  
H. Margonari ◽  
J. Loufoua ◽  
A. Ovize ◽  
X. André-Fouët ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Adenosine Receptors ◽  
Volume Overload ◽  
Coronary Artery Occlusion ◽  
Polymyxin B ◽  
Rabbit Heart ◽  
Artery Occlusion ◽  
Common Mechanism ◽  
Kinase C

We sought to determine whether stretch-induced preconditioning may be related to activation of adenosine receptors, ATP-sensitive K+([Formula: see text]) channels, and/or protein kinase C (PKC) in the rabbit heart. Anesthetized rabbits underwent 30 min of coronary artery occlusion followed by 3 h of reperfusion. Ischemic preconditioning was induced by one episode of 5 min of ischemia followed by 5 min of reperfusion, and stretch preconditioning was induced by a transient volume overload. The abilities of gadolinium (Gd3+), a blocker of stretch-activated channels, glibenclamide (Glib), a blocker of [Formula: see text] channels, 8-( p-sulfophenyl)-theophylline (8-SPT), a blocker of adenosine receptors, and polymyxin B (PMXB), an antagonist of PKC, to prevent the infarct size-limiting effect of stretch-induced preconditioning were evaluated. Because the infarct size-reducing effect of stretch occurred in the absence of ischemia and was prevented by previous administration of Gd3+, Glib, 8-SPT, and PMXB, we propose that activation of mechanosensitive ion channels protects the rabbit heart from subsequent sustained ischemic insult, likely through a mechanism that involves downstream activation of PKC, adenosine receptors, and/or [Formula: see text] channels.

Does protein kinase C play a role in ischemic preconditioning in rat hearts?

1995 ◽  
Vol 268 (1) ◽  
pp. H426-H431 ◽  
Author(s):  
Y. Li ◽  
R. A. Kloner
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Coronary Occlusion ◽  
Myocardial Infarct ◽  
Specific Inhibitor ◽  
Myocardial Infarct Size ◽  
Calphostin C ◽  
Kinase C

Protein kinase C (PKC) has been implicated in the cardioprotective effects of ischemic preconditioning in rabbits, but whether it plays a role in rats is unknown. We tested this preconditioning PKC theory by assessing whether the inhibition of PKC with calphostin C, a potent and specific inhibitor of PKC, can block the preconditioning effects in this model. Four groups of rats were studied: 1) control + vehicle, 2) control + calphostin C, 3) preconditioning + vehicle, and 4) preconditioning + calphostin C. All rats underwent 90 min of coronary occlusion followed by 4 h of reperfusion; in addition, preconditioned rats underwent three 3-min episodes of ischemia and 5 min of reperfusion before the 90 min of ischemia. Two injections of vehicle or calphostin C (0.1 mg/kg) were administered in intravenous boluses 29 min and 3 min before the 90-min coronary occlusion, i.e., one dose was given 5 min before preconditioning, and another dose was given between preconditioning and the sustained 90 min of ischemia in preconditioned rats. After 4 h of reperfusion, the area at risk (AR) was delineated by dye injection and area of necrosis was assessed by triphenyltetrazolium chloride staining. The electrocardiogram was recorded for the incidence of ventricular tachycardia (VT) and ventricular fibrillation. AR was similar in all four groups. In the nonpreconditioned control rats receiving vehicle, myocardial infarct size expressed as a percentage of the AR averaged 45.7 +/- 1.7%. Pretreatment with calphostin C had no effect on infarct size (48.9 +/- 3.4%) in nonpreconditioned control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Direct evidence that ischemic preconditioning does not cause protein kinase C translocation in rabbit heart

1996 ◽  
Vol 32 (6) ◽  
pp. 1064-1070 ◽  
Author(s):  
B SIMKHOVICH ◽  
K PRZYKLENK ◽  
S HALE ◽  
M PATTERSON ◽  
R KLONER
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
Direct Evidence ◽  
Rabbit Heart ◽  
Kinase C

Ischemic preconditioning attenuates apoptosis through protein kinase C in rat hearts

1999 ◽  
Vol 277 (5) ◽  
pp. H1997-H2001 ◽  
Author(s):  
Takayuki Okamura ◽  
Toshiro Miura ◽  
Hiroshi Iwamoto ◽  
Kazuyuki Shirakawa ◽  
Shuji Kawamura ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Triphenyltetrazolium Chloride ◽  
Calphostin C ◽  
Kinase C ◽  
Rat Hearts

To investigate the role of protein kinase C (PKC) in the mechanism of ischemic preconditioning (IP), infarct size and the incidence of apoptosis caused by ischemia-reperfusion were tested in four groups of Sprague-Dawley rats. Dimethyl sulfoxide (vehicle) or calphostin C (0.1 mg/ml) was administered 5 min before the 30-min coronary occlusion followed by a 6-h reperfusion. Three cycles of 3 min of ischemia followed by 3 min of reperfusion was performed as IP before the 30-min ischemia followed by a 6-h reperfusion with or without calphostin C pretreatment. Infarct size defined by triphenyltetrazolium chloride staining was reduced from 60 ± 2 to 26 ± 2% by IP ( P < 0.01), but the effect of IP was abolished by calphostin C (51 ± 3%). Apoptosis defined by in situ terminal deoxynucleotidyl transferase end-labeling (TUNEL) was reduced by IP from 44 ± 3 to 13 ± 2% in the subendocardial region ( P < 0.01). This effect of IP was abolished by calphostin C (42 ± 8%). Thus the effect of IP on reducing the infarct size and the incidence of apoptosis are both mediated by PKC in rat hearts.

Sign in / Sign up

Export Citation Format

Share Document