Phosphatidylinositol-3,4,5-trisphosphate stimulates Ca2+ elevation and Akt phosphorylation to constitute a major mechanism of thromboxane A2 formation in human platelets

Kassouf, Nick; Ambily, Archana; Watson, Steve P.; Hassock, Sheila; Authi, H; Srivastava, Salil; Watson, Steve P.; Authi, Kalwant S.

doi:10.1016/j.cellsig.2015.03.008

Cited by 9 publications

(3 citation statements)

References 54 publications

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“…These results are consistent with our previous studies (29,30) that show that elevated [Ca 2ϩ ] cyt is a major mediator for the stimulation of IEC migration and that PLC␥1 plays a critical role in regulating Ca 2ϩ homeostasis in response to injury. Induction of PLC␥1 by c-Jun increases [Ca 2ϩ ] cyt at least partially through IP3-sensitive signaling pathway because stimulation of PLC␥1 increases IP3 and promotes Ca 2ϩ influx attributable to SOCE (14,16). Consistent with our present findings, Huang et al (11) have recently reported that the ectopic overexpression of c-Jun enhances cell proliferation and migration in Schwann cells.…”

Section: Discussionsupporting

confidence: 92%

c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-γ1 transcription

Wang

Xiao

et al. 2017

American Journal of Physiology-Cell Physiology

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c-Jun is an activating protein 1 (AP-1) transcription factor and implicated in many aspects of cellular functions, but its exact role in the regulation of early intestinal epithelial restitution after injury remains largely unknown. Phospholipase C-γ1 (PLCγ1) catalyzes hydrolysis of phosphatidylinositol 4,5 biphosphate into the second messenger diacylglycerol and inositol 1,4,5 triphosphate, coordinates Ca store mobilization, and regulates cell migration and proliferation in response to stress. Here we reported that c-Jun upregulates PLCγ1 expression and enhances PLCγ1-induced Ca signaling, thus promoting intestinal epithelial restitution after wounding. Ectopically expressed c-Jun increased PLCγ1 expression at the transcription level, and this stimulation is mediated by directly interacting with AP-1 and CCAAT-enhancer-binding protein (C/EBP) binding sites that are located at the proximal region of the rat PLCγ1 promoter. Increased levels of PLCγ1 by c-Jun elevated cytosolic free Ca concentration and stimulated intestinal epithelial cell migration over the denuded area after wounding. The c-Jun-mediated PLCγ1/Ca signal also plays an important role in polyamine-induced cell migration after wounding because increased c-Jun rescued Ca influx and cell migration in polyamine-deficient cells. These findings indicate that c-Jun induces PLCγ1 expression transcriptionally and enhances rapid epithelial restitution after injury by activating Ca signal.

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Section: Discussionsupporting

confidence: 92%

c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-γ1 transcription

Wang

Xiao

et al. 2017

American Journal of Physiology-Cell Physiology

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“…Consistent with this, Nocella et al shows that the effects of LPS are inhibited by a TXA 2 antagonist [ 46 ]. Kassouf et al report that thrombin-induced TXB 2 formation (a stable TXA 2 metabolite) in platelets is suppressed by Akt inhibitor IV [ 51 ]. Here we propose that the pathway PI3K/Akt/ERK1/2/PLA 2 leads to TXA 2 formation following the exposure of platelets to LPS.…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide potentiates platelet responses via toll-like receptor 4-stimulated Akt-Erk-PLA2 signalling

et al. 2017

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Lipopolysaccharide (LPS) from the cell envelope of Gram-negative bacteria is a principal cause of the symptoms of sepsis. LPS has been reported to modulate the function of platelets although the underlying mechanisms of LPS action in these cells remain unclear. Platelets express the Toll-like receptor 4 (TLR4) which serves as a receptor for LPS, although the potential role of TLR4 and associated cell signalling in controlling platelet responses to LPS has not been extensively explored. In this study, we therefore investigated the actions of LPS prepared from different strains of Escherichia coli on platelet function, the underlying signalling mechanisms, and the potential role of TLR4 in orchestrating these. We report that LPS increased the aggregation of washed platelets stimulated by thromboxane (U46619) or GPVI collagen receptor agonists, effects that were prevented by a TLR4 antagonist. Associated with this, LPS enhanced fibrinogen binding, P-selectin exposure and reactive oxygen species (ROS) release. Increase of ROS was found to be important for the actions of LPS on platelets, since these were inhibited in the presence of superoxide dismutase or catalase. The effects of LPS were associated with phosphorylation of Akt, ERK1/2 and PLA2 in stimulated platelets, and inhibitors of PI3-kinase, Akt and ERK1/2 reduced significantly LPS enhanced platelet function and associated ROS production. Furthermore, inhibition of platelet cyclooxygenase or the thromboxane receptor, revealed an important role for thromboxane A2. We therefore conclude that LPS increases human platelet activation through a TLR4-PI3K-Akt-ERK1/2-PLA2 -dependent pathway that is dependent on ROS and TXA2 formation.

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“…Thromboxane A2 receptor (TXA2R), a member of the G protein-coupled receptor family (1), is broadly distributed in platelets (2), as well as epithelial (3), smooth muscle (4), glial and nerve cells in the brain (5). TXA2R is regarded as a traditional coagulation and inflammation-associated receptor, which is also closely associated with neurological disorders.…”

Section: Introductionmentioning

confidence: 99%

Thromboxane A2 receptor antagonist SQ29548 attenuates SH‑SY5Y neuroblastoma cell impairments induced by oxidative stress

Cai

Yan

et al. 2018

Int J Mol Med

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Thromboxane A2 receptor (TXA2R) serves a vital role in numerous neurological disorders. Our previous study indicated that SQ29548, an antagonist of TXA2R, attenuated the induced neuron damage in cerebral infarction animals; however, the underlying mechanism remains unknown. Certain studies revealed a new role of TXA2R in the regulation of oxidative stress, which is one of the basic pathological processes in neurological disorders. Thus, the present study attempted to examine whether the inhibition of TXA2R with SQ29548 helped to protect the nerve cells against oxidative stress. SQ29548 was utilized as a TXA2R antagonist, and relevant assays were performed to detect the cell viability, cellular reactive oxygen species (ROS) level, cell apoptosis, expression levels of superoxide dismutase‑2 (SOD2), catalase and caspases, and activation of mitogen‑activated protein kinase (MAPK) pathways. It was observed that hydrogen peroxide (H2O2) dose‑dependently reduced the viability of SH‑SY5Y cells. In addition, H2O2 raised the level of ROS in cells, inhibited the expression levels of SOD2 and catalase, and potentially enhanced cell apoptosis and the expression of caspases via activating the MAPK pathways. Pretreatment with SQ29548 not only rescued the viability of SH‑SY5Y cells, but also ameliorated the intracellular ROS level and the expression levels of SOD2 and catalase. Furthermore, it decreased the cell apoptosis and the expression of caspases, possibly via the inhibition of MAPK pathways. In conclusion, SQ29548, an antagonist of TXA2R, improved the antioxidant capacities of SH‑SY5Y cells and reduced the cell apoptosis through the inhibition of MAPK pathways.

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Phosphatidylinositol-3,4,5-trisphosphate stimulates Ca2+ elevation and Akt phosphorylation to constitute a major mechanism of thromboxane A2 formation in human platelets

Cited by 9 publications

References 54 publications

c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-γ1 transcription

c-Jun enhances intestinal epithelial restitution after wounding by increasing phospholipase C-γ1 transcription

Lipopolysaccharide potentiates platelet responses via toll-like receptor 4-stimulated Akt-Erk-PLA2 signalling

Thromboxane A2 receptor antagonist SQ29548 attenuates SH‑SY5Y neuroblastoma cell impairments induced by oxidative stress

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