Prostacyclin receptor-induced STAT3 phosphorylation in human erythroleukemia cells is mediated via Gαs and Gα16 hybrid signaling

Lo, Rico K.H.; Liu, Andrew M.F.; Wise, Helen; Wong, Yung Hou

doi:10.1016/j.cellsig.2008.08.003

Cited by 8 publications

(6 citation statements)

References 38 publications

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“…Additionally, our lab and other investigators have shown that the transcription factor STAT3 plays a key role in late PC by upregulating the expression of cardioprotective proteins such as iNOS, COX-2, HO1, and anti-apoptotic factors [7], [42], [96]. Recent studies in human erythroleukemia cells have shown that IP mediates STAT3 activation by stimulating STAT3 Tyr(705) and Ser(727) phosphorylation [97]. Thus, it appears that IP not only mediates signal transduction for COX-2 but also may act as a facilitator for feedback enhancement of multiple pathways mediating the late phase of PC.…”

Section: Discussionmentioning

confidence: 82%

“…The human IP receptor stimulates downstream activation primarily coupled to Gα s -adenylyl cyclase but also has been shown to act through Gq-mediated phospholipase C (PLC) activation [97]. We currently have a good understanding of the structure of IP based on homology modeling with the thromboxane A2 (TP) receptor and the cellular processing of IP from transcription to trafficking [99].…”

Section: Discussionmentioning

confidence: 99%

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The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning

Guo

Tukaye

et al. 2012

PLoS ONE

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BackgroundPharmacologic studies with cyclooxygenase-2 (COX-2) inhibitors suggest that the late phase of ischemic preconditioning (PC) is mediated by COX-2. However, nonspecific effects of COX-2 inhibitors cannot be ruled out, and the selectivity of these inhibitors for COX-2 vs. COX-1 is only relative. Furthermore, the specific prostaglandin (PG) receptors responsible for the salubrious actions of COX-2-derived prostanoids remain unclear.ObjectiveTo determine the role of COX-2 and prostacyclin receptor (IP) in late PC by gene deletion.MethodsCOX-2 knockout (KO) mice (COX-2−/−), prostacyclin receptor KO (IP−/−) mice, and respective wildtype (WT, COX-2+/+ and IP+/+) mice underwent sham surgery or PC with six 4-min coronary occlusion (O)/4-min R cycles 24 h before a 30-min O/24 h R.ResultsThere were no significant differences in infarct size (IS) between non-preconditioned (non-PC) COX-2+/+, COX-2−/−, IP+/+, and IP−/− mice, indicating that neither COX-2 nor IP modulates IS in the absence of PC. When COX-2−/− or IP−/− mice were preconditioned, IS was not reduced, indicating that the protection of late PC was completely abrogated by deletion of either the COX-2 or the IP gene. Administration of the IP selective antagonist, RO3244794 to C57BL6/J (B6) mice 30 min prior to the 30-min O had no effect on IS. When B6 mice were preconditioned 24 h prior to the 30-min O, IS was markedly reduced; however, the protection of late PC was completely abrogated by pretreatment of RO3244794.ConclusionsThis is the first study to demonstrate that targeted disruption of the COX-2 gene completely abrogates the infarct-sparing effect of late PC, and that the IP, downstream of the COX-2/prostanoid pathway, is a key mediator of the late PC. These results provide unequivocal molecular genetic evidence for an essential role of the COX-2/PGI2 receptor axis in the cardioprotection afforded by the late PC.

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Section: Discussionmentioning

confidence: 82%

Section: Discussionmentioning

confidence: 99%

The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning

Guo

Tukaye

et al. 2012

PLoS ONE

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“…PGI2 signals through G protein‐coupled IP receptors, which, in most cells, couple to G s proteins and activate adenylyl cyclase [25]. To analyse the functional expression of this ligand‐dependent signalling pathway in DCs, we measured cAMP levels.…”

Section: Resultsmentioning

confidence: 99%

Iloprost has potent anti‐inflammatory properties on human monocyte‐derived dendritic cells

Müller¹,

Dürk²,

Blumenthal³

et al. 2010

Clin Experimental Allergy

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“…This mechanism is consistent with investigations invoking both cAMP and cAMPindependent mechanisms in many instances. PROSTAGLANDIN RECEPTORS 507 and STAT3 phosphorylation (Lo et al, 2008), in addition to straightforward analysis of dose-dependent effects on cAMP formation (Accomazzo et al, 2002). PKAmediated switching from G s to G q and/or G i coupling, however, does not seem to be a universal phenomenon (Chow et al, 2003).…”

Section: Ip Receptorsmentioning

confidence: 99%

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

Woodward

Jones

Narumiya³

2011

Pharmacol Rev

391

414

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Prostacyclin receptor-induced STAT3 phosphorylation in human erythroleukemia cells is mediated via Gαs and Gα16 hybrid signaling

Abstract: 249Introduction: 750

Cited by 8 publications

References 38 publications

The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning

The COX-2/PGI2 Receptor Axis Plays an Obligatory Role in Mediating the Cardioprotection Conferred by the Late Phase of Ischemic Preconditioning

Iloprost has potent anti‐inflammatory properties on human monocyte‐derived dendritic cells

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

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