Cardioprotective Effects of 3-Phosphoinositide-Dependent Protein Kinase-1 on Hypoxic Injury in Cultured Neonatal Rat Cardiomyocytes and Myocardium in a Rat Myocardial Infarct Model

2012 ◽  
Vol 76 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Tae-Jin SHIM ◽  
Jang-Whan BAE ◽  
Yeon-Jung KIM ◽  
Dae Joong KIM ◽  
Kyung-Kuk HWANG ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Myocardial Infarct ◽  
Neonatal Rat ◽  
Dependent Protein Kinase ◽  
Rat Cardiomyocytes ◽  
Hypoxic Injury ◽  
Neonatal Rat Cardiomyocytes ◽  
Dependent Protein ◽  
Cardioprotective Effects ◽  
Myocardial Infarct Model

Abstract 307: Phospholipase Cε Is Involved in Gq-Dependent Protein Kinase D Activation in Cardiac Myocytes

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Alan Smrcka ◽  
Lianghui Zhang ◽  
Sundeep Malik
Keyword(s):  
Protein Kinase ◽  
G Proteins ◽  
Ventricular Myocytes ◽  
Neonatal Rat ◽  
Protein Kinase D ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Neonatal Rat Ventricular Myocytes ◽  
Phospholipase Cε

We previously demonstrated that PLCε is a critical mediator of endothelin-1 (ET-1)- and norepinephrine (NE)-dependent hypertrophy in neonatal rat ventricular myocytes (NRVMs). Both α-adrenergic and ET-1 receptors couple to Gq as well as other G proteins. To determine if PLCε is required for Gαq-dependent hypertrophy NRVMs were infected with adenoviruses expressing wtGαq and PLCε siRNA followed by measurement of hypertrophy. PLCε-siRNA significantly inhibited Gαq-induced increases in myocyte area and atrial natriuretic factor (ANF) mRNA expression. Similarly, disruption of PLCε association with perinuclear mAKAP inhibited Gαq-dependent hypertrophy. These data suggest that ET-1 and PE signal, at least in part, through Gαq and PLCε. To explore the functional role of PLCε in ET-1/Gq dependent hypertrophy, activation of protein kinase D (PKD) in NRVMs was assessed in response to ET-1. PLCε-siRNA significantly inhibited ET-1 induced PKD activation (∼50% inhibition). Disruption of PLCε-mAKAP interactions also significantly inhibited ET-1 induced PKD activation (∼50% inhibition). We propose that PLCε scaffolded to mAKAP at the nuclear envelope responds to Gαq-dependent, as well as other hypertrophic signals, to locally regulate PKD in a process that is critical for hypertrophy development.

scholarly journals Differential Role of Calcium/Calmodulin-dependent Protein Kinase II in Desflurane-induced Preconditioning and Cardioprotection by Metoprolol

2008 ◽  
Vol 109 (1) ◽  
pp. 72-80 ◽  
Author(s):  
Markus Lange ◽  
Thorsten M. Smul ◽  
Andreas Redel ◽  
Christopher Lotz ◽  
Virginija Jazbutyte ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infarct Size ◽  
Myocardial Infarct ◽  
Coronary Artery Occlusion ◽  
Myocardial Infarct Size ◽  
Area At Risk ◽  
Dependent Protein Kinase ◽  
Calcium Calmodulin Dependent ◽  
Protein Kinase Ii ◽  
Dependent Protein

Background Anesthetic preconditioning is mediated by beta- adrenergic signaling. This study tested the hypotheses that desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by calcium/calmodulin-dependent protein kinase II (CaMK II). Methods Pentobarbital-anesthetized New Zealand White rabbits were instrumented for measurement of systemic hemodynamics and subjected to 30 min of coronary artery occlusion followed by 3 h of reperfusion. Rabbits were assigned to receive vehicle (control), 0.2, 1.0, 1.75, or 2.5 mg/kg metoprolol for 30 min, or the CaMK II inhibitor KN-93 in the absence or presence of 1.0 minimum alveolar concentration desflurane. Protein expression of CaMK II, phospholamban, and phospho-phospholamban was measured by Western blotting. Myocardial infarct size and area at risk were measured with triphenyltetrazolium staining and patent blue, respectively. Results Baseline hemodynamics were not different among groups. Infarct size was 60 +/- 3% in control and significantly (* P < 0.05) decreased to 33 +/- 2%* by desflurane. The CaMK II inhibitor KN-93 did not affect infarct size (55 +/- 4%) but blocked desflurane-induced preconditioning (57 +/- 3%). Metoprolol at 0.2 and 1.0 mg/kg had no effect on infarct size (55 +/- 3% and 53 +/-3%), whereas metoprolol at 1.75 and 2.5 mg/kg reduced infarct size to 48 +/- 4%* and 39 +/- 5%*, respectively. Desflurane-induced preconditioning was attenuated by metoprolol at 0.2 mg/kg, leading to an infarct size of 46 +/- 5%*, and was completely abolished by metoprolol at 1.0, 1.75, and 2.5 mg/kg, resulting in infarct sizes of 51 +/- 3%, 52 +/- 3%, and 55 +/- 3%, respectively. Conclusions Desflurane-induced preconditioning is dose-dependently blocked by metoprolol and mediated by CaMK II.

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