Possible involvement of PPARγ in the regulation of basal channel opening of P2X7 receptor in cultured mouse astrocytes

Nagasawa, Kohei; Miyaki, Jun; Kido, Yuka; Higashi, Youichirou; Nishida, Kazuhiro; Fujimoto, Sadaki

doi:10.1016/j.lfs.2009.03.017

Cited by 10 publications

(9 citation statements)

References 41 publications

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“…Primary astrocyte cultures were prepared from the cortices of 1‐day‐old SJL‐strain mice (Japan Charles River, Kanagawa, Japan), as described previously (Nagasawa et al,2009a,b; Suzuki et al,2010). The experiments were approved by the Experimental Animal Research Committee of Kyoto Pharmaceutical University and were performed according to the Guidelines for Animal Experimention of Kyoto Pharmaceutical University.…”

Section: Methodsmentioning

confidence: 99%

“…After cells had been preincubated for 10 min in an appropriate buffer, the reaction was initiated by adding the 0.1 μM [ 3 H]adenosine, [ 3 H]NAD + or [ 14 C]NAD + in the presence or absence of various compounds at the designated concentrations to the cells. In the case of oxATP, an irreversible antagonist of P2X7R (Murgia et al,1993; Surprenant et al,1996), cells were first treated with 500 μM oxATP in BSS for 2–3 h, which was removed with three washes with warmed BSS prior to the uptake experiments (Nagasawa et al,2009a,b). After appropriate time intervals, the reaction was terminated by adding an excess volume of ice‐cold phosphate‐buffered saline (PBS) containing 1 mM unlabeled uridine.…”

Section: Methodsmentioning

confidence: 99%

“…YP uptake studies were performed according to the previously reported procedure (Nagasawa et al,2009a,b). In brief, after 10 min preincubation in BSS, the cells were incubated with 1 μM YP for 30 min in a 5% CO 2 incubator at 37°C.…”

Section: Methodsmentioning

confidence: 99%

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Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes

Okuda

Higashi

Nishida

et al. 2010

Glia

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Nucleotides and nucleosides play important roles by maintaining brain homeostasis, and their extracellular concentrations are mainly regulated by ectonucleotidases and nucleoside transporters expressed by astrocytes. Extracellularly applied NAD(+) prevents astrocyte death caused by excessive activation of poly(ADP-ribose) polymerase-1, of which the molecular mechanism has not been fully elucidated. Recently, exogenous NAD(+) was reported to enter astrocytes via the P2X7 receptor (P2X7R)-associated channel/pore. In this study, we examined whether the intact form of NAD(+) is incorporated into astrocytes. A large portion of extracellularly added NAD(+) was degraded into metabolites such as AMP and adenosine in the extracellular space. The uptake of adenine ring-labeled [(14)C]NAD(+), but not nicotinamide moiety-labeled [(3)H]NAD(+), showed time- and temperature-dependency, and was significantly enhanced on addition of apyrase, and was reduced by 8-Br-cADPR and ARL67156, inhibitors of CD38 and ectoapyrase, respectively, and P2X7R knockdown, suggesting that the detected uptake of [(14)C]NAD(+) resulted from [(14)C]adenosine acting as a metabolite of [(14)C]NAD(+). Pharmacological and genetic inhibition of P2X7R with brilliant blue G, KN-62, oxATP, and siRNA transfection resulted in a decrease of [(3)H]adenosine uptake, and the uptake was also reduced by low concentration of carbenoxolone and pannexin1 selective peptide blocker (10)panx. Taken together, these results indicate that exogenous NAD(+) is degraded by ectonucleotidases and that adenosine, as its metabolite, is taken up into astrocytes via the P2X7R-associated channel/pore.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes

Okuda

Higashi

Nishida

et al. 2010

Glia

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“…These discrepancies may be due to species variations, distinct intracellular machinery or differences in the protocol used to investigate a specific function in a same cell type (Faria et al, 2010). Other proteins have presented less divergent responses, such as: PKC (DonnellyRoberts et al, 2004;Faria et al, 2010;Shemon et al, 2004), Ca2+-insensitive Phospholipase A PLA (Chaib et al, 2000), caspase-1 and-3 (Donnelly- Roberts et al, 2004;Faria et al, 2010), PLD (Stunff & Raymond, 2007), phosphatidylinositol 4,5-bisphosphate (PIP 2 ) (Zhao et al, 2007), cytoskeleton components (Marques-da-Silva et al, 2011), PI3K (Faria et al, 2010), src tyrosine phosphorylation (Iglesias et al, 2008), Peroxisome proliferator-activated receptor gamma (PPAR gamma) (Nagasawa et al, 2009a) antagonists and intracellular Ca 2+ chelants (Faria et al, 2005(Faria et al, , 2010). …”

Section: Intracellular Signalling Pathways Associated With Large Condmentioning

confidence: 99%

Intracellular Signaling Pathways Integrating the Pore Associated with P2X7R Receptor with Other Large Pores

Ferreira¹,

Reis²,

Alves³

et al. 2012

Patch Clamp Technique

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“…These lipids and pathways include arachidonic acid (AA) and its metabolites in the immune response [2], the AA-mediated smooth muscular contractions and associated regulatory genes [3], and sphingosine-1-phosphate as a bioactive lipid mediator in asthma [4] and inflammation [5,6] that can activate a specific G protein-coupled receptor in both a paracrine and autocrine manner [4]. Other intracellular receptors translocate to the nucleus when activated by bioactive lipids, such as the peroxisome proliferator-activated receptors that are activated by fatty acids and their derivatives [7].…”

Section: Introductionmentioning

confidence: 99%

Lipid metabolism modulation by the P2X7 receptor in the immune system and during the course of infection: new insights into the old view

Costa-Junior

Marques-da-Silva

Vieira

et al. 2011

Purinergic Signalling

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For decades, scientists have described numerous protein pathways and functions. Much of a protein's function depends on its interactions with different partners, and those partners can change depending on the cell type or system. The P2X7 receptor (P2X7R) is one such multifunctional protein that is related to multiple partners and signaling pathways. The relationship between P2X7R and different enzymes involved in lipid metabolism represents a relatively new field in P2X7R research. This field of research began in epithelial cells and currently includes immune and nervous cells. The P2X7R-lipid metabolism pathway is related to many biological functions of P2X7R, such as cell death and pathogen clearance, and this signaling pathway may be involved in many functions that are dependent on bioactive lipids. In the present review, we will attempt to summarize data related to the P2X7R-lipid metabolism pathway, focusing on signaling pathways and their biological relevance to the immune system and infection.

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Possible involvement of PPARγ in the regulation of basal channel opening of P2X7 receptor in cultured mouse astrocytes

Cited by 10 publications

References 41 publications

Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes

Contribution of P2X7 receptors to adenosine uptake by cultured mouse astrocytes

Intracellular Signaling Pathways Integrating the Pore Associated with P2X7R Receptor with Other Large Pores

Lipid metabolism modulation by the P2X7 receptor in the immune system and during the course of infection: new insights into the old view

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