The Involvement of an ATP-Gated Ion Channel, P2X1, in Thymocyte Apoptosis

Chvatchko, Yolande; Valera, Soledad; Aubry, Jean‐Pierre; Renno, Toufic; Buell, Gary; Bonnefoy, Jean‐Yves

doi:10.1016/s1074-7613(00)80322-2

Cited by 106 publications

(79 citation statements)

References 47 publications

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“…In experiments reported by Chvatchko et al (1996), P2X 1 receptor expression was upregulated in thymocytes by apoptotic stimuli such as dexamethasone and SEB, a superantigen that ligates the T cell receptor. Furthermore, exogenous ATP caused apoptosis that was prevented by apyrase, an enzyme that degrades ATP.…”

Section: P2x Receptors and Cytotoxicity: A Laboratory Curiosity Or A mentioning

confidence: 95%

“…This lead us to suggest that plasma membrane ATP-gated channels may form a new family of ion channels with different permeability and ion selectivity, but linked by the common property of causing cell death under conditions of sustained stimulation (Murgia et al, 1992b). Recent data have confirmed that immune cells susceptible to ATP-mediated cytotoxicity express either P2X 1 or P2X 7 or maybe both (Buell et al, 1996c;Chvatchko et al, 1996;Dubyak et al, 1996). There has been some discussion in the past about the possibility that some cytolytic effect could be mediated via P2Y receptors.…”

Section: P2x Receptors and Cell Deathmentioning

confidence: 99%

“…It was immediately apparent that P2X 1 was nothing but the product of the RP-2 gene, which had previously been shown to be expressed during the early phases of apoptosis in rat thymocytes (Owen et al, 1991). Further support for a role of P2X 1 has recently come from the demonstration that mouse thymocytes exhibit an increase of P2X 1 mRNA content after in vitro dexamethasone treatment and in vivo challenge with the superantigen staphylococcal enterotoxin B (SEB) (Chvatchko et al, 1996 but see also Jiang et al, 1996, for an opposite view).…”

Section: P2x Receptors and Cell Deathmentioning

confidence: 99%

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Cytolytic P2X purinoceptors

et al. 1998

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Anedoctal evidence accumulated over almost 20 years has shown that many different cell types are killed by sustained exposure to high concentrations of extracellular ATP. The plasma membrane receptors involved have been pharmacologically characterized and cloned during the last 3 years, and named purinergic P2X. P2X receptors share an intriguing structural relatedness with Caenorhabditis elegans degenerins and mammalian amiloridesensitive Na channels (ENaCs). Depending on the ATP dose, length of stimulation and receptor subtype, P2X receptor stimulation may cause necrosis or apoptosis. The intracellular pathways activated are poorly known, but the perturbation in intracellular ion homeostasis clearly plays a major role. ICE proteases (caspases) are also triggered, nonetheless their activation is not requested for ATP-dependent cell death. The physiological meaning of P2X receptor-dependent cytotoxicity is not understood, but an involvement in immune-mediated reactions is postulated.

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Section: P2x Receptors and Cytotoxicity: A Laboratory Curiosity Or A mentioning

confidence: 95%

Section: P2x Receptors and Cell Deathmentioning

confidence: 99%

Section: P2x Receptors and Cell Deathmentioning

confidence: 99%

See 1 more Smart Citation

Cytolytic P2X purinoceptors

et al. 1998

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“…85 However, recent findings suggest that P2X receptor expression is not altered by dexamethasone treatment, that the P2X receptor agonist, ATP, does not induce apoptosis in thymocytes, and that P2X receptor antagonists do not block corticosteroid-induced apoptosis. 86 The potassium ion is also implicated in corticosteroidinduced apoptosis.…”

Section: Changes In Calcium and Potassium Homeostasismentioning

confidence: 99%

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

2002

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Glucocorticosteroid hormones induce apoptosis in lymphocytes. Therefore, glucocorticoids are commonly used as immunosuppressive and chemotherapeutic agents. This review examines many facets of the process by which glucocorticoids induce apoptosis. This process is divided into three stages, an initiation stage that involves glucocorticoid receptor-mediated gene regulation, a decision stage that involves the counterbalancing influence of prosurvival and proapoptotic factors, and the execution stage which involves caspase and endonuclease activation. Many aspects of glucocorticoid-induced apoptosis, such as mitochondrial dysfunction and caspase activation, are important steps in virtually all forms of apoptosis. But the process glucocorticoid-induced apoptosis differs from other forms of apoptosis in terms of initiation at the transcriptional level and involvement of the multicatalytic proteasome and calcium. Moreover, the abundant opportunity for crosstalk between the glucocorticoid receptor and other signaling pathways increases the complexity of glucocorticoid-induced apoptosis and its regulation.

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“…Moreover, ATP and P2X1 have been implicated in antigen-mediated thymocyte apoptosis or programmed cell death [20], which is a developmental response of CD4 + CD8 + thymocytes that have inappropriately high antigen receptor affinity. In fact, most CD4 + CD8 + thymocytes do not reach functional maturity, but rather die either by negative selection, a TCR-mediated process, or by neglect, which is a default response that occurs in the absence of positive or negative selection [21].…”

Section: Introductionmentioning

confidence: 99%

ATP-evoked Ca2+ transients and currents in murine thymocytes: possible role for P2X receptors in death by neglect

et al. 1999

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The P2X family of ATP receptors (P2XR) have been implicated in thymocyte death in vitro and in vivo. We characterized ATP-evoked Ca 2+ transients and membrane currents in thymocytes to better understand the role of P2XR during thymocyte development. ATP 4-, but not UTP or GTP, activated a sustained non-selective cation current in voltage-clamped CD4 -CD8 -and CD4 + CD8 + thymocytes that was reversed by apyrase, which hydrolyzes ATP, and by the P2XR antagonists suramin and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS). The more selective P2XR agonist § g -methylene ATP activated a smaller rapidly decaying current in both thymocyte populations. Reverse transcription-PCR results indicate that P2X1, P2X2, P2X6, and/or P2X7 are expressed in thymocytes. Finally, we used PPADS to examine the role of P2XR during thymocyte development in situ. PPADS-treated thymi yielded significantly more thymocytes (38 %), due to a selective increase in CD4 + CD8 + cells. Together these data suggest that one or more PPADS-sensitive P2XR (P2X1, P2X2, P2X7) are involved in thymocyte apoptosis, and we propose more specifically a role associated with death by neglect.

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The Involvement of an ATP-Gated Ion Channel, P2X1, in Thymocyte Apoptosis

Cited by 106 publications

References 47 publications

Cytolytic P2X purinoceptors

Cytolytic P2X purinoceptors

Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

ATP-evoked Ca2+ transients and currents in murine thymocytes: possible role for P2X receptors in death by neglect

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