Extracellular nucleotide derivatives protect cardiomyocytes against hypoxic stress

Golan, Or GolanO.; Issan, Yossi; Isak, Ahuva; Leipziger, Jens; Robaye, Bernard; Shainberg, Asher

doi:10.1016/j.bcp.2011.02.007

Cited by 15 publications

(11 citation statements)

References 33 publications

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“…After ischemia-reperfusion injury, the coronary vasodilator effect of Ap 4 A is impaired, probably due to reduced responsiveness of P2Y receptors to Ap 4 A (García-Villalón et al, 2011). Extracellular tri-and diphosphates were claimed to be responsible for cardioprotection against hypoxic damage, probably by preventing free radical formation (Golan et al, 2011). Ap3A, a vasoactive mediator stored in platelet granules, induces coronary vasodilation, which is attenuated by ischemia-reperfusion due to the functional impairment of P2Y receptors (Garcia-Villalón et al, 2012).…”

Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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Section: Ischemiamentioning

confidence: 99%

Purinergic Signaling and Blood Vessels in Health and Disease

2013

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“…After ischaemia-reperfusion injury, the coronary vasodilator effect of Ap 4 A was shown to be impaired, probably due to reduced responsiveness of P2YR to Ap 4 A [614]. Extracellular tri-and di-phosphates were claimed to be responsible for cardioprotection against hypoxic damage, probably by preventing free radical formation [615]. Diadenosine triphosphate, a vasoactive mediator stored in platelet granules, induces coronary vasodilation, which is attenuated by ischaemia-reperfusion due to the functional impairment of P2YR [616] A protective role of E-NTPDase 1/CD39 in ischaemiareperfusion injury has also been shown.…”

Section: Ischaemiamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

120

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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“…In our previous work using P2Y 2 receptor-knockout mice, this receptor was found to mediate the anti-ischemic cardioprotection induced by UTP [5,6]. In the absence of the P2Y 2 receptor, the protective effect of UTP was abolished.…”

Section: Introductionmentioning

confidence: 99%

“…The hypoxic conditions lasted for 120 min in a hypoxic incubator in which the atmosphere was replaced by the inert gas argon (100 %) in glucose-free media [5]. The hypoxic damage was characterized at the end of the hypoxic period through biochemical and morphological evaluations.…”

Section: +mentioning

confidence: 99%

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P2Y2 receptor agonist with enhanced stability protects the heart from ischemic damage in vitro and in vivo

Hochhauser

Cohen

Waldman

et al. 2013

Purinergic Signalling

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Extracellular nucleotides acting via P2 receptors play important roles in cardiovascular physiology/pathophysiology. Pyrimidine nucleotides activate four G protein-coupled P2Y receptors (P2YRs): P2Y 2 and P2Y 4 (UTP-activated), P2Y 6 , and P2Y 14 . Previously, we showed that uridine 5′-triphosphate (UTP) activating P2Y 2 R reduced infarct size and improved mouse heart function after myocardial infarct (MI). Here, we examined the cardioprotective role of P2Y 2 R in vitro and in vivo following MI using uridine-5′-tetraphosphate δ-phenyl ester tetrasodium salt (MRS2768), a selective and more stable P2Y 2 R agonist. Cultured rat cardiomyocytes pretreated with MRS2768 displayed protection from hypoxia [as revealed by lactate dehydrogenase (LDH) release and propidium iodide (PI) binding], which was reduced by P2Y 2 R antagonist, AR-C118925 (5-((5-(2,8-dimethyl-5H-dibenzo [a,d][7]annulen-5-yl)-2-oxo-4-thioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl)-N-(1H-tetrazol-5-yl)furan-2-carboxamide). In vivo, echocardiography and infarct size staining of triphenyltetrazolium chloride (TTC) in 3 groups of mice 24 h post-MI: sham, MI, and MI+MRS2768 indicated protection. Fractional shortening (FS) was higher in MRS2768-treated mice than in MI alone (40.0±3.1 % vs. 33.4±2.7 %, p < 0.001). Troponin T and tumor necrosis factor-α (TNF-α) measurements demonstrated that MRS2768 pretreatment reduced myocardial damage (p<0.05) and c-Jun phosphorylation increased. Thus, P2Y 2 R activation protects cardiomyocytes from hypoxia in vitro and reduces post-ischemic myocardial damage in vivo.

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Extracellular nucleotide derivatives protect cardiomyocytes against hypoxic stress

Cited by 15 publications

References 33 publications

Purinergic Signaling and Blood Vessels in Health and Disease

Purinergic Signaling and Blood Vessels in Health and Disease

Cardiac purinergic signalling in health and disease

P2Y2 receptor agonist with enhanced stability protects the heart from ischemic damage in vitro and in vivo

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