Preconditioning of Isolated Rat Heart Is Mediated by Protein Kinase C

Mitchell, Max B.; Meng, Xianzhong; Ao, Lihua; Brown, James M.; Harken, Alden H.; Banerjee, Anirban

doi:10.1161/01.res.76.1.73

Cited by 367 publications

(171 citation statements)

References 48 publications

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“…1A) in both groups of hearts (20 Ϯ 4 versus 19 Ϯ 3 mm Hg; n ϭ 6, p ϭ not significant). Independent laboratories have shown that pretreatment with brief ischemia, here termed TIP, prevents cardiac injury during prolonged ischemia reperfusion in association with PKC activation (9,10). In this study, we found that TIP improved LVDP recovery during reperfusion (Fig.…”

Section: Normal Base-line Morphology and In Vivo Cardiac Function In supporting

confidence: 57%

“…Stimulation of ␣ 1 -adrenergic receptors activates numerous signaling pathways within ventricular myocytes including mitochondrial K ATP channels (28), glucose transporters (42), and PKC isozymes (9). However, it is unclear which of the pathways protect acutely against injury and which of them contribute chronically to myocardial pathology.…”

Section: Discussionmentioning

confidence: 99%

“…1B). Cardioprotection in association with PKC activation has also been observed after stimulation with pharmacological agents such as adenosine A 1 receptor agonists (15), ␦ 1 -opioid receptor agonists (12,26), ethanol (19,27), sphingosine-1-phosphate (20), and ␣ 1 -adrenergic receptor agonists (9,28). Here we pretreated with PHE at concentrations selective for ␣ 1 -adrenergic receptor stimulation and improved LVDP recovery during reperfusion in wild-type but not PKC⑀ KO hearts (Fig.…”

Section: Normal Base-line Morphology and In Vivo Cardiac Function In mentioning

confidence: 99%

“…Ischemic preconditioning is also known to activate PKC␦ and PKC⑀ in ex vivo rat hearts (9,10). However, PKC␦-mediated signaling during ischemia reperfusion has not been fully explored.…”

Section: Contractile Recovery and Infarction After Pretreatment With mentioning

confidence: 99%

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Preservation of Base-line Hemodynamic Function and Loss of Inducible Cardioprotection in Adult Mice Lacking Protein Kinase Cϵ

Gray

Zhou

Schafhalter-Zoppoth

et al. 2004

Journal of Biological Chemistry

104

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Signaling pathways involving protein kinase C isozymes are modulators of cardiovascular development and response to injury. Protein kinase C⑀ activation in cardiac myocytes reduces necrosis caused by coronary artery disease. However, it is unclear whether protein kinase C⑀ function is required for normal cardiac development or inducible protection against oxidative stress. Protein kinase C␦ activation is also observed during cardiac preconditioning. However, its role as a promoter or inhibitor of injury is controversial. We examined hearts from protein kinase C⑀ knock-out mice under physiological conditions and during acute ischemia reperfusion. Null-mutant and wild-type mice displayed equivalent base-line morphology and hemodynamic function. Targeted disruption of the protein kinase C⑀ gene blocked cardioprotection caused by ischemic preconditioning and ␣ 1 -adrenergic receptor stimulation. Protein kinase C␦ activation increased in protein kinase C⑀ knock-out myocytes without altering resistance to injury. These observations support protein kinase C⑀ activation as an essential component of cardioprotective signaling. Our results favor protein kinase C␦ activation as a mediator of normal growth. This study advances the understanding of cellular mechanisms responsible for preservation of myocardial integrity as potential targets for prevention and treatment of ischemic heart disease.Coronary artery disease and chronic heart failure are important causes of death worldwide. Cellular signaling pathways that regulate cardiovascular development and responses to injury, particularly those involving protein kinase C (PKC) 1 isozymes, are under intense investigation. For example, MochlyRosen et al. (1) found that activation of PKC⑀ translocation in transgenic mouse hearts caused physiological hypertrophy and reduced the size of individual myocytes. In contrast, postnatal inhibition of PKC⑀ translocation produced lethal dilated cardiomyopathy and increased cardiac myocyte volumes (1). Wu et al. (2) later observed that activation of PKC⑀ translocation in G␣ q transgenic hearts improved contractile function. Conversely, inhibition of PKC⑀ translocation converted the G␣ q hypertrophic phenotype to a dilated cardiomyopathy (2). However, no previous investigations established whether PKC⑀ activation was an absolute requirement for normal cardiac growth or whether compensatory changes in the expression of other myocardial proteins developed in the absence of PKC⑀-mediated signaling.Two lines of evidence support the hypothesis that PKC⑀ activation promotes myocardial resistance to injury during periods of oxidative stress. First, both ischemic preconditioning and pharmacological approaches that induce cardioprotection increase PKC⑀ immunoreactivity and kinase function in cell particulate fractions (3). Second, transgenic expression of a constitutively active PKC⑀ (4) or a peptide agonist of PKC⑀ translocation (5) reduces cardiac myocyte necrosis during ischemia reperfusion. However, it is unclear whether PKC⑀ activation represe...

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Section: Normal Base-line Morphology and In Vivo Cardiac Function In supporting

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Normal Base-line Morphology and In Vivo Cardiac Function In mentioning

confidence: 99%

Section: Contractile Recovery and Infarction After Pretreatment With mentioning

confidence: 99%

See 2 more Smart Citations

Preservation of Base-line Hemodynamic Function and Loss of Inducible Cardioprotection in Adult Mice Lacking Protein Kinase Cϵ

Gray

Zhou

Schafhalter-Zoppoth

et al. 2004

Journal of Biological Chemistry

104

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show abstract

“…Furthermore, activation of PKC can protect the heart from ischaemic injury, while PKC inhibitors block the cardioprotective effect of ischaemic preconditioning in experimental animals and in human myocytes [55][56][57][58][59][60]. On the other hand, fenoterol has known inotrophic and chronotrophic effdcts as well as other electrophysiologica l influences [40][41][42]; these are enhanced under hypoxic conditions [61].…”

Section: Discussionmentioning

confidence: 99%

Inhibition by fenoterol of human eosinophil functions includingβ2-adrenoceptor-independent actions

Tachibana

Katô

Kimura

et al. 2002

Clinical and Experimental Immunology

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SUMMARYAgonists at b 2 adrenoceptors are used widely as bronchodilators in treating bronchial asthma. These agents also may have important anti-inflammatory effects on eosinophils in asthma. We examined whether widely prescribed b 2 -adrenoceptor agonists differ in ability to suppress stimulus-induced eosinophil effector functions such as superoxide anion (O 2 -) generation and degranulation. To examine involvement of cellular adhesion in such responses, we also investigated effects of b 2 agonists on cellular adhesion and on CD11b expression by human eosinophils. O 2 -was measured using chemiluminescence. Eosinophil degranulation and adhesion were assessed by a radioimmunoassay for eosinophil protein X (EPX). CD11b expression was measured by flow cytometry. Fenoterol inhibited platelet-activating factor (PAF)-induced O 2 -generation by eosinophils significantly more than salbutamol or procaterol. Fenoterol partially inhibited PAF-induced degranulation by eosinophils similarly to salbutamol or procaterol. Fenoterol inhibited phorbol myristate acetate (PMA)-induced O 2 -generation and degranulation by eosinophils, while salbutamol or procaterol did not. Fenoterol inhibition of PMA-induced O 2 -generation was not reversed by ICI-118551, a selective b 2 -adrenoceptor antagonist. Fenoterol, but not salbutamol or procaterol, significantly inhibited PAF-induced eosinophil adhesion. Fenoterol inhibited O 2 -generation and degranulation more effectively than salbutamol or procaterol; these effects may include a component involving cellular adhesion. Inhibition also might include a component not mediated via b 2 adrenoceptors.

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Organ Preconditioning

Raeburn¹

2001

Arch Surg

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Preconditioning of Isolated Rat Heart Is Mediated by Protein Kinase C

Cited by 367 publications

References 48 publications

Preservation of Base-line Hemodynamic Function and Loss of Inducible Cardioprotection in Adult Mice Lacking Protein Kinase Cϵ

Preservation of Base-line Hemodynamic Function and Loss of Inducible Cardioprotection in Adult Mice Lacking Protein Kinase Cϵ

Inhibition by fenoterol of human eosinophil functions includingβ2-adrenoceptor-independent actions

Organ Preconditioning

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