Amplification of human platelet activation by surface pannexin‐1 channels

Taylor, Kirk A.; Wright, Joy R.; Vial, Céline; Evans, Richard J.; Mahaut‐Smith, Martyn P.

doi:10.1111/jth.12566

Cited by 55 publications

(86 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pannexins are a family with three member proteins, related to gap junctions, which form channels enhancing ATP release and Ca +2 uptake that are mechanically sensitive (Taylor et al, 2015). Recent studies have shown that activation of pannexin-1 enhances platelet activation (Taylor et al, 2014). Future studies are needed to further clarify the role of pannexins, and other potential shear-sensitive channels, as to their contribution to shear-mediated platelet activation.…”

Section: Mechano-activation – Activation Of Shear-sensitive Channelsmentioning

confidence: 99%

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

Slepian

Sheriff

Hutchinson

et al. 2017

Journal of Biomechanics

View full text Add to dashboard Cite

Shear-mediated platelet activation (SMPA) is central in thrombosis of implantable cardiovascular therapeutic devices. Despite the morbidity and mortality associated with thrombosis of these devices, our understanding of mechanisms operative in SMPA, particularly in free flowing blood, remains limited. Herein we present and discuss a range of emerging mechanisms for consideration for “free flow” activation under supraphysiologic shear. Further definition and manipulation of these mechanisms will afford opportunities for novel pharmacologic and mechanical strategies to limit SMPA and enhance overall implant device safety.

show abstract

Section: Mechano-activation – Activation Of Shear-sensitive Channelsmentioning

confidence: 99%

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

Slepian

Sheriff

Hutchinson

et al. 2017

Journal of Biomechanics

View full text Add to dashboard Cite

show abstract

“…One possible explanation of these data is that [Cl − ] o is required for efficient release of ATP and/or ADP from the platelet, but we failed to observe a change in dense granule secretion (Figure 2c). Pannexin-1 has been shown to activate in response to elevation of intracellular Ca 2+ ([Ca 2+ ] i ) [20], facilitating cytosolic ATP release [14]. It has been suggested that ADP release may occur via a similar mechanism [21].…”

Section: Discussionmentioning

confidence: 99%

“…Proteomic [10] and transcriptomic [11] analyses have since identified numerous anion channels that may be expressed by platelets. Of these, functional expressions of CLIC1 (Intracellular Cl − channel-1) [12], TMEM16F [13], and pannexin-1 [14] have been confirmed. Indicative of a hemostatic role for anion channels, CLIC1- and TMEM16F-deficient mice have associated platelet-related bleeding phenotypes [12, 13].…”

Section: Introductionmentioning

confidence: 99%

“…Indicative of a hemostatic role for anion channels, CLIC1- and TMEM16F-deficient mice have associated platelet-related bleeding phenotypes [12, 13]. Additionally, pannexin-1 channels have been shown to amplify platelet activation responses to threshold agonist concentrations [14]. These ATP-permeable channels are associated with inflammatory conditions and may contribute to atherosclerosis [15].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extracellular chloride is required for efficient platelet aggregation

et al. 2017

View full text Add to dashboard Cite

Anion channels perform a diverse range of functions and have been implicated in ATP release, volume regulation, and phosphatidylserine exposure. Platelets have been shown to express several anion channels but their function is incompletely understood. Due to a paucity of specific pharmacological blockers, we investigated the effect of extracellular chloride substitution on platelet activation using aggregometry and flow cytometry. In the absence of extracellular chloride, we observed a modest reduction of the maximum aggregation response to thrombin or collagen-related peptide. However, the rate of aggregation was substantially reduced in a manner that was dependent on the extracellular chloride concentration and aggregation in the absence of chloride was noticeably biphasic, indicative of impaired secondary signaling. This was further investigated by targeting secondary agonists with aspirin and apyrase or by blockade of the ADP receptor P2Y12. Under these conditions, the rates of aggregation were comparable to those recorded in the absence of extracellular chloride. Finally, we assessed platelet granule release by flow cytometry and report a chloride-dependent element of alpha, but not dense, granule secretion. Taken together these data support a role for anion channels in the efficient induction of platelet activation, likely via enhancement of secondary signaling pathways.

show abstract

“…Knockdown of Panx-1 in mice also has the effect of reducing tumor size in vivo [8]. Moreover, Panx-1 is highly expressed in human platelets, and Panx-1 channels can promote the aggregation of platelets, which is a risk factor of cancer metastasis, by enhancing Ca 2+ influx and ATP release [9]. How do these conflicts occur?…”

mentioning

confidence: 99%

A new perspective of mechanosensitive pannexin-1 channels in cancer metastasis: clues for the treatment of other stress-induced diseases

2016

ABBS

View full text Add to dashboard Cite

Cancer metastasis is a process that cancer cells deviate from the primary site and spread to the other areas to form new colonies, which is the leading cause of death in cancer patients. During metastatic progression, circulating cancer cells lodge within the microvasculature of end organs, where most of them die from mechanical deformation. However, cancer cells can survive from mechanical deformation by unknown mechanisms. Recently, Furlow et al.[1] identified a mutation truncated form of pannexin-1 (Panx-1), PANX1 1-89 , which was significantly enriched in highly metastatic cancer cells. PANX1 augmented Panx-1 channel-mediated adenosine triphosphate (ATP) release and enhanced the efficiency of metastasis by promoting metastatic breast cancer cells survival during physical deformation. Additionally, carbenoxolone (CBX), a Panx-1 inhibitor, was proved to reduce the efficiency of breast cancer metastasis. These results suggested that Panx-1 is one of the molecular bases for metastatic cell survival in microvasculature-induced biomechanical trauma [1]. In 2000, three members of pannexins, including Panx-1, Panx-2, and Panx-3, have been found to be new members of gap-junctions' family [2]. Panx-1 was ubiquitously expressed in human tissues. Subsequent studies further revealed that Panx-1 forms single-pass membrane channels that connect the intracellular and extracellular compartments rather than forming intercellular channels spanning the two plasma membranes, which is mainly different from classical gap junctions [3]. Physiologically, Panx-1 channels are mainly involved in the efflux of ATP and regulate cellular inflammasomes [4]. Many studies indicated that Panx-1 is related to epilepsy, neuropathic pain, painful musculoskeletal diseases, ischemia injury, myocardial fibrosis, overactivity of the human bladder, and cancers [5][6][7][8][9][10][11][12][13] (Fig. 1 ).The beneficial or aggravating role of Panx-1 in cancer remains controversial. Lai et al. [5] reported that Panx-1 plays a tumor-suppressive role in vitro and in vivo. Reverse transcription polymerase chain reaction analysis revealed that C6 cells do not express Panx-1. However, stable expression of Panx-1 in C6 glioma cells significantly inhibits cell growth, proliferation, and motility in vitro [5]. Besides, Panx-1 is an important intratumor biomechanical environment regulator that accelerates the dynamic assembly of multicellular C6 glioma aggregates [6]. Panx-1 also significantly reduces the tumor size in athymic nude mice [5,6]. Derangere et al. [7] reported that caspase-1-dependent colon cancer cell pyroptosis is mainly induced through the interaction with Panx-1. These data supported that Panx-1 has a tumorsuppressor property, while some other studies indicated that Panx-1 promotes the development of cancer. Penuela et al. [8] found that Panx-1 is upregulated in B16 melanoma cells rather than in normal melanocytes. Furthermore, Panx-1-depleted B16 melanoma cells exhibit reduced cell migration and growth, resembling normal melanocytes. Knockdown o...

show abstract

Amplification of human platelet activation by surface pannexin‐1 channels

Cited by 55 publications

References 51 publications

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis

Extracellular chloride is required for efficient platelet aggregation

A new perspective of mechanosensitive pannexin-1 channels in cancer metastasis: clues for the treatment of other stress-induced diseases

Contact Info

Product

Resources

About