Chapter 22 Brain hypoxia: Effects of ATP and adenosine

Nieber, K; Eschke, Dagmar; Brand, A

doi:10.1016/s0079-6123(08)63563-3

Cited by 42 publications

(29 citation statements)

References 83 publications

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“…This behavior is not surprising because, although some similarities exist between the promoter regions of 5-LO and FLAP genes, the former has the characteristic of a housekeeping gene and it has been reported that these two genes do not necessarily follow the same pattern of expression or regulation when studied in the same cell type (41,26). Interestingly, this first evidence of the P2X 7 capability to upregulate an important protein of leukotriene biosynthesis in astrocytes is consistent with the reported P2X 7 capability to increase the expression and/or the production of different proinflammatory mediators in astrocytes and astrocytoma cells (38,58,23).…”

Section: A) B)supporting

confidence: 83%

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P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

Ballerini

Ciccarelli

Caciagli

et al. 2005

Int J Immunopathol Pharmacol

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* Equally contributed to this paperAstrocytes have been recognized as important elements in controlling inflammatory as well as immune processes in the central nervous system (CNS). Recently, glial cells have been shown to produce cysteinyl leukotrienes (CysLTs) which are known lipid mediators of inflammation and whose extracellular concentrations rise under different pathological conditions in the brain. In the same conditions also extracellular concentrations of ATP dramatically increase reaching levels able to activate P2X 7 ionotropic receptors for which an emerging role in neuroinflammation and neurodegeneration has been claimed. RT-PCR analysis showed that primary cultures of rat brain astrocytes express P2X 7 receptors. Application of the selective P2X7 agonist benzoyl-benzolyATP(BzATP) markedly increased [Ca"], which was mediated by a calcium influx from the extracellular milieu. The P2X 7 antagonist, oATP,suppressed the BzATP-induced calcium increase. Consistent with the evidence that increased calcium levels activate the leukotriene biosynthetic pathway, challenge of astrocytes with either the calcium ionophore A23187 or BzATP significantly increased CysLT production and the cell pre-treatment with EGTA abolished these effects. Again the P2X7 antagonist prevented the BzATP-mediated CysLT efflux, whereas the astrocyte pretreatment with MK-571, a CysLT I receptor antagonist, was ineffective. The astrocyte pre-treatment with a cocktail of inhibitors of ATP binding cassette (ABC) proteins reduced the BzATP-mediated CysLT production confirming that ABC transporters are involved in the release of CysLTs. The astrocyte P2X 7-evoked rise of CysLT efflux was abolished in the presence of MK-886, an inhibitor of 5-lipoxygenase activating protein (FLAP) whose expression, along with that of 5'-lipoxygenase (5-LO) was reported by Northern Blot analysis. The stimulation ofP2X 7 induced an up-regulation of FLAP mRNA that was reduced by the antagonist oATP. These data suggest that in rat brain cultured astrocytes P2X 7 ATP receptors may participate in the control of CysLT release thus further supporting a role for extracellular ATP as an integral component of the inflammatory brain response.Inflammation is involved in several neurological diseases including brain injury, cerebral ischemia, multiple sclerosis,Alzheimer's and Parkinson's diseases (31,47,35). Neuroinflammation is characterized by the activation of both microglia and astrocytes (45). Glial cells, including astrocytes, are reported to produce

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Section: A) B)supporting

confidence: 83%

“…These effects were abolished by cell pre-treatment with the P2X 7 receptor antagonist oATP (6). Moreover, P2X 7 activation in astrocytes has been reported to increase the expression of MCP-l, a chemokine which is upregulated after CNS trauma (38).…”

mentioning

confidence: 97%

P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

Ballerini

Ciccarelli

Caciagli

et al. 2005

Int J Immunopathol Pharmacol

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“…Thus, spinal cord trauma causes the release of ATP around the damaged area, as measured by bioluminescence, and results in cell death of nearby neurons and oligodendrocytes that is strongly attenuated by P2X 7 antagonists (Wang et al, 2004). In addition, other studies have shown that trauma liberates large amounts of ATP (Nieber et al, 1999;Ray et al, 2002) (for review, see Anderson and Nedergaard, 2006).…”

Section: Discussionmentioning

confidence: 99%

P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

Matute¹,

Torre²,

et al. 2007

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Oligodendrocyte death and demyelination are hallmarks of multiple sclerosis (MS).Here we show that ATP signaling can trigger oligodendrocyte excitotoxicity via activation of calcium-permeable P2X 7 purinergic receptors expressed by these cells. Sustained activation of P2X 7 receptors in vivo causes lesions that are reminiscent of the major features of MS plaques, i.e., demyelination, oligodendrocyte death, and axonal damage. In addition, treatment with P2X 7 antagonists of chronic experimental autoimmune encephalomyelitis (EAE), a model of MS, reduces demyelination and ameliorates the associated neurological symptoms. Together, these results indicate that ATP can kill oligodendrocytes via P2X 7 activation and that this cell death process contributes to EAE. Importantly, P2X 7 expression is elevated in normal-appearing axon tracts in MS patients, suggesting that signaling through this receptor in oligodendrocytes may be enhanced in this disease. Thus, P2X 7 receptor antagonists may be beneficial for the treatment of MS.

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“…In the normal condition, the extracellular ATP level is detected at low levels and modulated by ectoATPases. However, increases in extracellular ATP levels were observed in the pathophysiological conditions, such as ischemia, tissue injury and hypoxia [10,11,13], probably leading to a higher amount of extracellular ATP than in a normal state. Loss of ectoATPase activity in the pathological conditions provided additional evidence for the accumulation of extracelluar ATP [14,15].…”

Section: Discussionmentioning

confidence: 99%

“…Release of ATP into extracellular space has been detected following high-frequency neuronal stimulation [9], ischemia [10,11] and mechanical forces [12]. Several lines of evidence suggest that released ATP can act as an excitotoxin in certain pathological conditions, including ischemia, hypoxia, and tissue injury [1,10,13]. Ubiquitous ecto-ATPases, known as ATP hydrolyzing enzymes, regulate extracellular ATP concentration in normal condition, whereas inflammatory reactions or oxidative stress inhibits ecto-ATPases activity, resulting in the accumulation of extracellular ATP [14,15].…”

Section: Introductionmentioning

confidence: 99%

ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors

et al. 2002

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The present study examined the in vivo e¡ects of ATP on the striatum of Sprague^Dawley rats. Intrastriatal administration of ATP produced dose-dependent striatal lesions as con¢rmed by cresyl violet staining. Additional immunostaining using neuronal nuclear protein (NeuN), OX-42 and GFAP antibodies revealed that ATP caused death of both neurons and glial cells. The nonmetabolizable ATP analogue ATPgS and P2X receptor agonist a,b-methylene ATP (a,b-MeATP) mimicked ATP e¡ects, whereas either P2Y receptor agonist ADP or P1 receptor agonist adenosine did not. The P2 receptor antagonist reactive blue 2, but not pyridoxal-phosphate-6 -azophenyl-2 0 ,4 0 -disulphonic acid (PPADS) attenuated ATP-induced striatal injury. These results suggest that intrastriatal administration of ATP causes P2X receptor-mediated cell death in the striatum and support the hypothesis that extracellular ATP can be an important mediator of neuropathological events of brain injuries. NeuroReport13:1611^1615

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Chapter 22 Brain hypoxia: Effects of ATP and adenosine

Cited by 42 publications

References 83 publications

P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors

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Chapter 22 Brain hypoxia: Effects of ATP and adenosine

Cited by 42 publications

References 83 publications

P2X7Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X7Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X7Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis

ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors

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Resources

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P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X₇Receptor Activation in Rat Brain Cultured Astrocytes Increases the Biosynthetic Release of Cysteinyl Leukotrienes

P2X₇Receptor Blockade Prevents ATP Excitotoxicity in Oligodendrocytes and Ameliorates Experimental Autoimmune Encephalomyelitis