MED1101: A new dialdehydic compound regulating P2×7 receptor cell surface expression in U937 cells

Muzzachi, Stefania; Blasi, Antonella; Ciani, Elena; Favia, Maria; Cardone, Rosa Angela; Marzulli, Domenico; Reshkin, Stephan J.; Merizzi, Giulia; Casavola, Valeria; Soleti, Antonio; Guerra, Lorenzo

doi:10.1111/boc.201200088

Cited by 8 publications

(6 citation statements)

References 88 publications

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“…Other compounds may also be of value in modulating P2X7 expression. Recently, the dialdehydic compound 2-[1-(6-amminopurin-9-il)-2-osso-etossi]prop-2-enale (MED1011) was developed and shown to downregulate the expression and function of P2X7 in macrophages by causing the internalization of P2X7 in these cells (Muzzachi et al, 2013). Moreover, the medicinal extract from Aloe vera has been shown to downregulate P2X7 expression in macrophages to attenuate IL-1b secretion (Budai et al, 2013).…”

Section: Modulators Of P2x7 Receptor Expressionmentioning

confidence: 99%

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

2014

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Section: Modulators Of P2x7 Receptor Expressionmentioning

confidence: 99%

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

2014

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“…Pannexin-1 has been implicated as the protein associated with the P2X7R pore [ 30 , 36 ]. For this reason, we examined whether our methodology was specific for P2X7R pore activity.…”

Section: Resultsmentioning

confidence: 99%

“…The J774.G8 macrophage cell line, which was previously demonstrated by us to natively express P2X7R and the Pannexin-1 channel [ 10 ], as well as other P2 subtypes, including P2X4R and P2Y1, P2Y2 and P2Y4 receptors [ 29 ]. And U937 human monocyte cell line [ 30 , 31 ], were routinely maintained in RPMI 1640 medium supplemented with 10% fetal bovine serum at 37°C under an atmosphere containing 5% CO 2 . Every three days, the medium was changed, and the cells were adjusted to a density of 4x10 6 cells per 150 cm 2 cell culture flask (Corning).…”

Section: Methodsmentioning

confidence: 99%

An Improved Method for P2X7R Antagonist Screening

et al. 2015

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ATP physiologically activates the P2X7 receptor (P2X7R), a member of the P2X ionotropic receptor family. When activated by high concentrations of ATP (i.e., at inflammation sites), this receptor is capable of forming a pore that allows molecules of up to 900 Da to pass through. This receptor is upregulated in several diseases, particularly leukemia, rheumatoid arthritis and Alzheimer's disease. A selective antagonist of this receptor could be useful in the treatment of P2X7R activation-related diseases. In the present study, we have evaluated several parameters using in vitro protocols to validate a high-throughput screening (HTS) method to identify P2X7R antagonists. We generated dose-response curves to determine the EC50 value of the known agonist ATP and the ICs50 values for the known antagonists Brilliant Blue G (BBG) and oxidized ATP (OATP). The values obtained were consistent with those found in the literature (0.7 ± 0.07 mM, 1.3-2.6 mM and 173-285 μM for ATP, BBG and OATP, respectively). The Z-factor, an important statistical tool that can be used to validate the robustness and suitability of an HTS assay, was 0.635 for PI uptake and 0.867 for LY uptake. No inter-operator variation was observed, and the results obtained using our improved method were reproducible. Our data indicate that our assay is suitable for the selective and reliable evaluation of P2X7 activity in multiwell plates using spectrophotometry-based methodology. This method might improve the high-throughput screening of conventional chemical or natural product libraries for possible candidate P2X7R antagonist or agonist

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“…Many of studies have indicated that activation of P2X7 receptors can promote migration in different types of cells, such as monocytes [26], tumor cells [27], and epithelial cells [28]. P2X7 receptors have also been shown to promote the migration of cultured glial cells [29].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

“…P2X7 receptors have also been shown to promote the migration of cultured glial cells [29]. Moreover, P2X7 receptor activation was demonstrated to trigger extracellular calcium ion influx, then activate intracellular kinases, such as MAPK [26,28] and Akt [30], or increase the expression of matrix metalloproteinase 9 [29], thereby facilitating cell migration. Moreover, Fyn kinase, one member of the Src family, is involved in OPC migration [31,32].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration

Feng

Gao

et al. 2015

Purinergic Signalling

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Recruitment of oligodendrocyte precursor cells (OPCs) to the lesions is the most important event for remyelination after central nervous system (CNS) injury or in demyelinating diseases. However, the underlying molecular mechanism is not fully understood. In the present study, we found high concentrations of ATP could increase the number of migrating OPCs in vitro, while after pretreatment with oxidized ATP (a P2X7 receptor antagonist), the promotive effect was attenuated. The promotive effect of 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate (BzATP) (a P2X7 receptor agonist) was more potent than ATP. After incubation with BzATP, the activity of Fyn, one member of the Src family of kinases, was enhanced. Moreover, the interaction between P2X7 and Fyn was identified by co-immunoprecipitation. After blocking the activity of Fyn or downregulating the expression of Fyn, the migration of OPCs induced by BzATP was inhibited. These data indicate that P2X7 receptors/Fyn may mediate ATP-induced OPC migration under pathological conditions.

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MED1101: A new dialdehydic compound regulating P2×7 receptor cell surface expression in U937 cells

Cited by 8 publications

References 88 publications

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

The P2X7 Receptor Channel: Recent Developments and the Use of P2X7 Antagonists in Models of Disease

An Improved Method for P2X7R Antagonist Screening

P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration

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