Extracellular NAADP affords cardioprotection against ischemia and reperfusion injury and involves the P2Y11-like receptor

Djerada, Zoubir; Peyret, Hélène; Dukic, Sylvain; Millart, Hervé

doi:10.1016/j.bbrc.2013.03.089

Cited by 23 publications

(19 citation statements)

References 32 publications

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“…The treatment of the ischemic heart with NAADP (to induce Ca 2+ release from AS) exerted protective effects on the heart, as demonstrated by the improvement in cardiac hemodynamics and contractility and the decrease in cardiac enzyme levels. Although not directly connected to the effect of AS Ca 2+ , in line with our findings, Djerada et al [8] demonstrated a decrease in I/R injury when the heart was pretreated with NAADP. The same group reported for the first time a significant increase in the extracellular NAADP concentration during heart ischemia [8].…”

Section: Discussionsupporting

confidence: 93%

“…Although not directly connected to the effect of AS Ca 2+ , in line with our findings, Djerada et al [8] demonstrated a decrease in I/R injury when the heart was pretreated with NAADP. The same group reported for the first time a significant increase in the extracellular NAADP concentration during heart ischemia [8]. Interestingly, the release of Ca 2+ from AS is protective to the heart, in contrast to the known effect of SR Ca 2+ release [29].…”

Section: Discussionsupporting

confidence: 93%

See 1 more Smart Citation

Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

Khalaf

Babiker

2016

J Physiol Biochem

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We and others have demonstrated a protective effect of pacing postconditioning (PPC) against ischemia/reperfusion (I/R) injury. However, the mechanisms underlying this protection are not completely clear. In the present study, we evaluated the effects of calcium release from the sarcoplasmic reticulum (SR) and the novel intracellular acidic stores (AS). Isolated rat hearts (n = 6 per group) were subjected to coronary occlusion followed by reperfusion using a modified Langendorff system. Cardiac hemodynamics and contractility were assessed using a data acquisition program, and cardiac injury was evaluated by creatine kinase (CK) and lactate dehydrogenase (LDH) levels. Hearts were subjected to 30 min of regional ischemia, produced by ligation of the left anterior descending (LAD) coronary artery, followed by 30 min of reperfusion. The hearts were also subjected to PPC (3 cycles of 30 s of left ventricle (LV) pacing alternated with 30 s of right atrium (RA) pacing) and/or were treated during reperfusion with agonists or antagonists of release of calcium from SR or AS. PPC significantly (P < 0.05) normalized LV, contractility, and coronary vascular dynamics and significantly (P < 0.001) decreased heart enzyme levels compared to the control treatments. The blockade of SR calcium release resulted in a significant (P < 0.01) recovery in LV function and contractility and a significant reduction in CK and LDH levels (P < 0.01) when applied alone or in combination with PPC. Interestingly, the release of calcium from AS alone or in combination with PPC significantly improved LV function and contractility (P < 0.05) and significantly decreased the CK and LDH levels (P < 0.01) compared to the control treatments. An additive effect was produced when agonism of calcium release from AS or blockade of calcium release from the SR was combined with PPC. Calcium release from AS and blockade of calcium release from the SR protect the heart against I/R. Combining calcium release from acidic stores or blockade of calcium release from the SR with PPC produced a synergistic protective effect.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

Khalaf

Babiker

2016

J Physiol Biochem

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“…In conclusion, our results suggest that DCs P2Y11R could play a pivotal role in mediating the inflammatory response following I/R. Of interest, some authors reported a protective role of P2Y11R stimulation in myocardial I/R (55,56). These data combined with our observations support the idea that using pharmacological P2Y11R agonists during I/R episode could provide beneficial effects after organ transplantation and acute myocardial infarction.…”

Section: Discussionsupporting

confidence: 86%

Hypoxia/Reoxygenation Inhibits P2Y11 Receptor Expression and Its Immunosuppressive Activity in Human Dendritic Cells

Chadet

Ivanès

Benoist

et al. 2015

The Journal of Immunology

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High concentrations of extracellular ATP (eATP) resulting from cell damage may be found during an ischemia/reperfusion (I/R) episode at the site of injury. eATP activates purinergic receptors in dendritic cells (DCs) and may inhibit inflammation. This immunosuppressive activity could be of interest in the field of I/R, which is an inflammatory condition involved in myocardial infarction, stroke, and solid organ transplantation. However, the specific purinergic receptor responsible for this effect remains to be identified. In this study, we report that eATP induced maturation of human monocyte-derived DCs. Additionally, eATP inhibited IL-12 production whereas IL-10 levels remained unchanged in activated DCs. These effects were prevented by the P2Y11R antagonist NF340. Interestingly, a 5-h hypoxia prevented the effects of eATP on cytokine production whereas a 1-h hypoxia did not affect the eATP-mediated decrease of IL-12 and IL-6. We showed a time-dependent downregulation of P2Y11R at both mRNA and protein levels that was prevented by knocking down hypoxia-inducible factor-1α. In this study, we showed an immunosuppressive role of P2Y11R in human DCs. Additionally, we demonstrated that the time-dependent downregulation of P2Y11R by hypoxia orientates DCs toward a proinflammatory phenotype that may be involved in post-I/R injuries as observed after organ transplantation.

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“…It indicated that P2Y4 was not involved in RCECs. Several new types of P2Y receptors have not been detected on the corneal endothelium, such as P2Y11 and P2Y14 [Barrett et al, 2013;Djerada et al, 2013]. We postulate that high concentrations of ATP might activate receptors other than P2Y2 that have opposite effects.…”

Section: Discussionmentioning

confidence: 99%

Adenosine Triphosphate-Induced Rabbit Corneal Endothelial Cell Proliferation in vitro via the P2Y2-PI3K/Akt Signaling Axis

Chen

Shao²,

Lu³

et al. 2014

Cells Tissues Organs

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Purpose: To investigate the effect of the ATP-P2Y2-PI3K/Akt signaling axis on promoting rabbit corneal endothelial cell (RCEC) proliferation in vitro. Methods: Five concentrations of adenosine triphosphate (ATP; 1, 10, 25, 50 and 100 μM) were added to RCECs, and the cell proliferation was detected using Cell Counting Kit-8 (CCK8) and Ki67 immunohistochemical staining. Other P2Y2 receptor agonists and antagonists were added to the cells, and the proliferation effect was evaluated using CCK8 to determine the involvement of the P2Y2 receptor. Changes in the expression of phosphorylated Akt in RCECs treated with different concentrations of extracellular ATP and the duration of extracellular ATP on Akt phosphorylation were investigated using Western blotting. The pharmacological profiles with or without the PI3K/Akt pathway inhibitors were also determined using Western blotting. Results: We found that 10 μM ATP strongly promoted RCEC proliferation in vitro. Additionally, 25 μM ATP had a proliferation effect, whereas other concentrations (1, 50 and 100 μM) had no effect compared with the control group. Selective P2Y2 receptor agonists (UTP, ATPγS and Ap₄A) showed the same promotion effect, while P2Y2 antagonists and PI3K/Akt inhibitors inhibited the effect of ATP. Moreover, phosphorylated Akt could be induced by the addition of extracellular ATP at all five concentrations and lasted for 1 h. This phosphorylation was prevented by PI3K/Akt inhibitors and a P2Y2 antagonist. Conclusions: These findings showed that 10 μM ATP markedly promoted RCEC proliferation via the P2Y2-PI3K/Akt signaling axis.

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Extracellular NAADP affords cardioprotection against ischemia and reperfusion injury and involves the P2Y11-like receptor

Cited by 23 publications

References 32 publications

Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

Discrepancy in calcium release from the sarcoplasmic reticulum and intracellular acidic stores for the protection of the heart against ischemia/reperfusion injury

Hypoxia/Reoxygenation Inhibits P2Y11 Receptor Expression and Its Immunosuppressive Activity in Human Dendritic Cells

Adenosine Triphosphate-Induced Rabbit Corneal Endothelial Cell Proliferation in vitro via the P2Y2-PI3K/Akt Signaling Axis

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