Mechanisms of P2X<sub>7</sub> receptor-mediated ERK1/2  phosphorylation in human astrocytoma cells

Gendron, Fernand‐Pierre; Neary, Joseph T.; Theiss, Patty; Sun, Grace Y.; González, Fernando; Weisman, Gary A.

doi:10.1152/ajpcell.00286.2002

Cited by 100 publications

(91 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Erk1/2 phosphorylation is also Ca 2ϩ -independent in rat P2X7R-transfected HEK 293 cells (55) and parotid acinar cells (59). Calcium influx is, on the other hand, needed for Erk1/2 activation in astrocytoma (32) and Jurkat cells (54). Using various deletion mutants of rat P2X7R, Amstrup et al (55) have concluded that the N-terminal domain of P2X7R is essential for triggering Erk1/2 phosphorylation, whereas the C terminus domain controls Ca 2ϩ entry, suggesting that the two events may be dissociable in many cell types.…”

Section: Discussionmentioning

confidence: 99%

“…However, neither p56 lck nor p59 fyn represent the relevant kinase. The involvement of Src family tyrosine kinase(s) in P2X7R signaling has been described for rat microglia (60) and for Jurkat lymphoma (54) and astrocytoma cells (32).…”

Section: Discussionmentioning

confidence: 99%

“…Thus, in macrophages (30) and thymocytes (31), calcium-dependent phospholipase D activation is observed, but this enzymatic activity is not involved in cell death. The role of P2X7R in controlling protein kinase activities (32)(33)(34), the generation of superoxide (35), as well as activation of transcriptional factors (36,37) has been tested in various cellular models. However, the relationship between these biochemical events and cell death has not been fully characterized.…”

mentioning

confidence: 99%

See 2 more Smart Citations

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

Auger

Motta

Benihoud

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

Extracellular ATP (ATPe) binds to P2X7 receptors (P2X7R) expressed on the surface of cells of hematopoietic lineage, including murine thymocytes. Activation of P2X7R by ATPe results in the opening of cation-specific channels, and prolonged ATPe exposure leads to the formation of non-selective pores enabling transmembrane passage of solutes up to 900 Da. In the presence of ATPe, P2X7R-mediated thymocyte death is due primarily to necrosis/lysis and not apoptosis, as measured by the release of lactate dehydrogenase indicative of a loss of plasma membrane integrity. The present study is focused on the identification of P2X7R signaling mediators in ATP-induced thymocyte necrosis/lysis. Thus, extracellular signal-regulated protein kinase 1/2 (Erk1/2) phosphorylation was found to be required for cell lysis, and both events were independent of ATP-induced calcium influx. P2X7R-dependent thymocyte death involved the chronological activation of Src family tyrosine kinase(s), phosphatidylinositol 3-kinase, the mitogen-activated protein (MAP) kinase Erk1/2 module, and the proteasome. Although independent of this signaling cascade, non-selective pore formation may modulate ATP-mediated thymocyte death. These results therefore suggest a role for both activation of MAP kinase Erk1/2 and non-selective pore opening in P2X7R-induced thymocyte death. Extracellular ATP interacts with P2 purinergic receptors that are expressed on a wide spectrum of tissues. Two classes of P2 receptors have been identified, the G-protein-coupled seventransmembrane P2Y receptors and the P2X ligand-gated cation channels (1). Seven members of the P2X receptor family have been cloned, which share the same predicted structure with two transmembrane-spanning domains, an extracellular loop and intracellular N-and C-terminal tails. The P2X7 receptor (P2X7R) 1 differs from the other P2X receptors; in particular, its C-terminal domain is 200 amino acids longer and it does not heteropolymerize with other members of the P2X family (2). Brief exposure to millimolar concentrations of ATP in its fully dissociated tetra-anionic form, ATP 4Ϫ

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

Auger

Motta

Benihoud

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus, the events regulating MAP kinase cascades in activated macrophages are important for the understanding of inflammatory mediator production. In this regard, it is known that ERK1/ ERK2, p38, and JNK1/JNK2 are activated in response to P2X 7 agonists in a variety of cell types [8,[45][46][47][48]. Because P2X 7 action has been linked to inflammatory mediator production [8,49,50], it is likely that nucleotide-mediated MAP kinase activation modulates proinflammatory responses.…”

Section: Introductionmentioning

confidence: 99%

Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation

Pfeiffer

Guerra

Hill

et al. 2007

Free Radical Biology and Medicine

View full text Add to dashboard Cite

Macrophage activation is critical in the innate immune response and can be regulated by the nucleotide receptor P2X 7 . In this regard, P2X 7 signaling is not well understood but has been implicated in controlling reactive oxygen species (ROS) generation by various leukocytes. Although ROS can contribute to microbial killing, the role of ROS in nucleotide-mediated cell signaling is unclear. In this study, we report that the P2X 7 agonists ATP and 3′-O-(4-benzoyl) benzoic ATP (BzATP) stimulate ROS production by RAW 264.7 murine macrophages. These effects are potentiated in lipopolysaccharide-primed cells, demonstrating an important interaction between extracellular nucleotides and microbial products in ROS generation. In terms of nucleotide receptor specificity, RAW 264.7 macrophages that are deficient in P2X 7 are greatly reduced in their capacity to generate ROS in response to BzATP treatment (both with and without LPS priming), thus supporting a role for P2X 7 in this process. Because MAP kinase activation is key for nucleotide regulation of macrophage function, we also tested the hypothesis that P2X 7 -mediated MAP kinase activation is dependent on ROS production. We observed that BzATP stimulates MAP kinase (ERK1/ ERK2, p38, and JNK1/JNK2) phosphorylation, and that the antioxidants N-acetyl-cysteine and ascorbic acid strongly attenuate BzATP-mediated JNK1/JNK2 and p38 phosphorylation but only slightly reduce BzATP-induced ERK1/ERK2 phosphorylation. These studies reveal that P2X 7 can contribute to macrophage ROS production, that this effect is potentiated upon lipopolysaccharide exposure, and that ROS are important participants in the extracellular nucleotide-mediated activation of several MAP kinase systems.

show abstract

“…In astrocytes and other glial cells, accumulating evidence indicate that the receptor is coupled to both ERK and p38 mitogen-activated protein kinase (MAPK) phosphorylation [14][15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Different properties of P2X7 receptor in hippocampal and cortical astrocytes

Bianco

Colombo

Saglietti

et al. 2009

Purinergic Signalling

View full text Add to dashboard Cite

P2X 7 receptor is a ligand-gated ion channel, which can induce the opening of large membrane pores. Here, we provide evidence that the receptor induces pore formation in astrocytes cultured from cortex, but not from the hippocampus. Furthermore, P2X 7 receptor activation promptly induces p38 mitogen-activated protein kinase (MAPK) phosphorylation in cortical but not in hippocampal astrocytes. Given the role of p38 MAPK activation in pore opening, these data suggest that defective coupling of the receptor to the enzyme could occur in hippocampal cultures. The different capabilities of the receptor to open membrane pores cause relevant functional consequences. Upon pore formation, caspase-1 is activated and pro-IL1-β is cleaved and released extracellularly. The receptor stimulation does not result in interleukin-1beta secretion from hippocampal astrocytes, although the pro-cytokine is present in the cytosol of lipopolysaccharide-primed cultures. These results open the possibility that activation of P2X 7 receptors differently influences the neuroinflammatory processes in distinct brain regions.

show abstract

Mechanisms of P2X₇ receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells

Cited by 100 publications

References 54 publications

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation

Different properties of P2X7 receptor in hippocampal and cortical astrocytes

Contact Info

Product

Resources

About

Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells

Cited by 100 publications

References 54 publications

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

A Role for Mitogen-activated Protein KinaseErk1/2 Activation and Non-selective Pore Formation in P2X7 Receptor-mediated Thymocyte Death

Nucleotide receptor signaling in murine macrophages is linked to reactive oxygen species generation

Different properties of P2X7 receptor in hippocampal and cortical astrocytes

Contact Info

Product

Resources

About

Mechanisms of P2X₇ receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells