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Zhaoxia Wang - One of the best experts on this subject based on the ideXlab platform.
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the Purinergic Receptor p2y g protein coupled 2 p2ry2 gene associated with essential hypertension in japanese men
Journal of Human Hypertension, 2010Co-Authors: Zhaoxia Wang, Tomohiro Nakayama, Naoyuki Sato, Yoichi Izumi, Yuji Kasamaki, Masakatsu Ohta, Masayoshi Soma, Noriko Aoi, Yukio OzawaAbstract:The Purinergic Receptor P2Y, G-protein coupled, 2 ( P2RY2 ) gene associated with essential hypertension in Japanese men
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Purinergic Receptor p2y g protein coupled 2 p2ry2 gene is associated with cerebral infarction in japanese subjects
Hypertension Research, 2009Co-Authors: Zhaoxia Wang, Tomohiro Nakayama, Naoyuki Sato, Yoichi Izumi, Yuji Kasamaki, Masakatsu Ohta, Masayoshi Soma, Mai Yamaguchi, Noriko AoiAbstract:G-protein-coupled Purinergic Receptor P2Y2 (P2RY2) has an important role in the process of atherosclerosis related to cerebral infarction (CI). The aim of this study was to investigate the relationship between the P2RY2 gene and CI through a haplotype-based case-control study, including the separate analysis of two gender groups. A total of 237 CI patients and two control groups (control 1, 254; control 2, 255) were genotyped for five single nucleotide polymorphisms (SNPs) in the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Among women, the distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between the CI patients and the control 1 group (P=0.043) and between the CI patients and the control 2 group (P=0.029). Logistic regression analysis showed that the GG genotype of rs4944832 was significantly more prevalent in the female CI patients than in the control 1 (P=0.021) and control 2 groups (P=0.005). For all subjects, the overall distribution of the haplotype established by rs1783596-rs4382936-rs10898909 was significantly different between the CI patients and the control 1 group (P=0.027). For all subjects, the frequency of the T-A-G haplotype (rs1783596-rs4382936-rs10898909) was also significantly higher (P=0.031), whereas the frequency of the T-C-G haplotype (rs1783596-rs4382936-rs10898909) was significantly lower (P=0.029) in the CI patients than in the control 1 group. The present results indicate that the T-A-G haplotype of the human P2RY2 gene is a susceptibility haplotype for CI in Japanese subjects, and that the GG genotype is a genetic marker for CI, particularly in Japanese women.
Jinsheng Sun - One of the best experts on this subject based on the ideXlab platform.
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characterization of udp activated Purinergic Receptor p2y6 involved in japanese flounder paralichthys olivaceus innate immunity
International Journal of Molecular Sciences, 2018Co-Authors: Nan Wang, Gaixiang Hao, Jinsheng SunAbstract:Uridine 5’-diphosphate (UDP)-activated Purinergic Receptor P2Y6 is a member of a G-protein-coupled Purinergic Receptor family that plays an important role in mammalian innate immunity. However, the role of the P2Y6 Receptor (P2Y6R) in fish immunity has not been investigated. In this report, we characterized a P2Y6R gene from Japanese flounder (Paralichthys olivaceus) and examined its role in fish innate immunity. Sequence analysis reveals that the Japanese flounder P2Y6R protein is conserved and possesses four potential glycosylation sites. Quantitative real-time RT-PCR analysis shows that P2Y6R is broadly distributed in all examined Japanese flounder tissues with dominant expression in the liver. In addition, P2Y6R gene expression was up-regulated in head kidney macrophages (HKMs) upon lipopolysaccharides (LPS) and poly(I:C) stimulations but down-regulated by LPS challenge in peripheral blood leukocytes (PBLs). Furthermore, pharmacological inhibition of the endogenous P2Y6 Receptor activity by the potently selective P2Y6R antagonist, MRS 2578, greatly up-regulated pro-inflammatory cytokine interleukin (IL)-1β, IL-6 and TNF-α gene expression in PBL cells treated with UDP. Moreover, LPS- and poly(I:C)-induced gene expression of IL-1β and TNF-α in Japanese flounder PBL cells was attenuated significantly by inhibition of P2Y6R activity with antagonist MRS 2578. Collectively, we, for the first time, showed the involvement of functional Purinergic P2Y6R in fish innate immunity.
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Characterization of UDP-Activated Purinergic Receptor P2Y6 Involved in Japanese Flounder Paralichthys olivaceus Innate Immunity
MDPI AG, 2018Co-Authors: Nan Wang, Gaixiang Hao, Jinsheng SunAbstract:Uridine 5’-diphosphate (UDP)-activated Purinergic Receptor P2Y6 is a member of a G-protein-coupled Purinergic Receptor family that plays an important role in mammalian innate immunity. However, the role of the P2Y6 Receptor (P2Y6R) in fish immunity has not been investigated. In this report, we characterized a P2Y6R gene from Japanese flounder (Paralichthys olivaceus) and examined its role in fish innate immunity. Sequence analysis reveals that the Japanese flounder P2Y6R protein is conserved and possesses four potential glycosylation sites. Quantitative real-time RT-PCR analysis shows that P2Y6R is broadly distributed in all examined Japanese flounder tissues with dominant expression in the liver. In addition, P2Y6R gene expression was up-regulated in head kidney macrophages (HKMs) upon lipopolysaccharides (LPS) and poly(I:C) stimulations but down-regulated by LPS challenge in peripheral blood leukocytes (PBLs). Furthermore, pharmacological inhibition of the endogenous P2Y6 Receptor activity by the potently selective P2Y6R antagonist, MRS 2578, greatly up-regulated pro-inflammatory cytokine interleukin (IL)-1β, IL-6 and TNF-α gene expression in PBL cells treated with UDP. Moreover, LPS- and poly(I:C)-induced gene expression of IL-1β and TNF-α in Japanese flounder PBL cells was attenuated significantly by inhibition of P2Y6R activity with antagonist MRS 2578. Collectively, we, for the first time, showed the involvement of functional Purinergic P2Y6R in fish innate immunity
T K Harden - One of the best experts on this subject based on the ideXlab platform.
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expression of a cloned p2y Purinergic Receptor that couples to phospholipase c
Molecular Pharmacology, 1994Co-Authors: Theresa M Filtz, Jose L Boyer, Robert A Nicholas, T K HardenAbstract:P2Y Purinergic Receptors previously have been shown to couple either to activation of phospholipase C through a pertussis toxin-insensitive mechanism or to inhibition of adenylyl cyclase through pertussis toxin-sensitive members of the G1 family of G proteins. These and other pharmacological data strongly suggest that multiple P2Y Purinergic Receptors exist. Webb et al. [FEBS Lett. 324:219-225 (1993)] cloned a cDNA that, when expressed in frog oocytes, displayed the general pharmacological characteristics of a P2Y Purinergic Receptor but whose second messenger linkage was not resolved. We have now cloned the meleagrid (turkey) homologue of the previously cloned chick P2Y Purinergic Receptor and have stably expressed it in a heterologous human cell line (1321N1 astrocytoma cells) to establish its signaling properties. The Purinergic Receptor agonist 2-methylthio-ATP (2MeSATP) stimulated a marked activation of phospholipase C in 1321N1 cells stably expressing the meleagrid Receptor. The order of potency of a series of analogues of ATP and ADP for stimulation of phospholipase C by the Receptor expressed in 1321N1 cells [2MeSATP = 2-methylthio-ADP > adenosine 5'-O-(2-thio)diphosphate > ADP > 2-chloro-ATP = adenosine 5'-O-(3-thio)triphosphate > or = ATP > adenylyl-imidodiphosphate > UTP] was similar to that observed for P2Y Purinergic Receptors in turkey erythrocytes and many other tissues and was markedly different from those of the P2U and P2X Purinergic Receptor subtypes. Stimulation of inositol lipid hydrolysis by P2Y Purinergic agonists was not affected by preincubation of cells with pertussis toxin. In contrast to its marked effects on phospholipase C activity, 2MeSATP caused only a small and variable inhibition of cAMP accumulation. Ribonuclease protection analysis of turkey tissues showed that this P2Y Purinergic Receptor is most highly expressed in blood and brain. Taken together, these results indicate that a phospholipase-C-activating P2Y Purinergic Receptor has been cloned and stably expressed in 1321N1 astrocytoma cells.
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identification of a p2y Purinergic Receptor that inhibits adenylyl cyclase
Journal of Pharmacology and Experimental Therapeutics, 1993Co-Authors: Jose L Boyer, Eduardo R Lazarowski, Xiaohua Chen, T K HardenAbstract:Adenine nucleotides inhibited isoproterenol- and forskolin-stimulated cyclic AMP accumulation in C6-2B rat glioma cells. Inhibition occurred in the presence of a phosphodiesterase inhibitor, and no effect of adenine nucleotides was observed in direct measurements of phosphodiesterase activity in intact cells. Pretreatment of C6-2B glioma cells with pertussis toxin blocked the inhibitory effects of P2Y-Purinergic Receptor agonists. The pharmacological specificity for a series of ATP and ADP analogs (2-methylthioadenosine 5'-triphosphate > or = 2-methylthioadenosine 5'-diphosphate > adenosine 5'-O-(2-thiodiphosphate) > 2-chloro-adenosine 5'-triphosphate = ADP = adenosine 5'-O-(3-thiotriphosphate) > ATP > UTP) was similar to that expected of a P2Y-Purinergic Receptor; the P2X-Purinergic Receptor agonists, alpha,beta-methyleneadenosine 5'-triphosphate and beta,gamma-methylene-adenosine 5'-triphosphate, had no effect. Because activation of phospholipase C occurs in response to P2-Purinergic Receptor activation in many target tissues, the effects of P2Y-Receptor agonists on inositol phosphate accumulation were measured in C6-2B cells. No evidence for P2Y-Purinergic Receptor-mediated regulation of inositol lipid metabolism was observed under conditions where muscarinic cholinergic Receptor activation or AIF4-markedly increased inositol phosphate accumulation. These results suggest that a P2-Purinergic Receptor subtype with distinct signaling properties exists on C6-2B rat glioma cells. Although this Receptor expresses the general pharmacological specificity of a phospholipase C-coupled P2Y-Purinergic Receptor, it may represent a unique Receptor subtype since it inhibits adenylyl cyclase.
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solubilization of a guanine nucleotide sensitive form of the p2y Purinergic Receptor
Molecular Pharmacology, 1991Co-Authors: R A Jeffs, C L Cooper, T K HardenAbstract:P2Y-Purinergic Receptors were solubilized from turkey erythrocyte plasma membranes with the nonionic detergent digitonin. Adenosine 59-O-(2-[35S]thiodiphosphate) ([35S]ADP beta S) labeled a single population of soluble high affinity sites (Kd = 12.9 nM; Bmax = 4.5 pmol/mg of protein) in an equilibrium binding assay; adenine nucleotide analogs competitively inhibited [35S]ADP beta S binding with a rank order of potency consistent with that for P2Y-Purinergic Receptors. Radioligand binding to solubilized P2Y-Purinergic Receptors was noncompetitively inhibited by guanine nucleotides with a rank order of potency that was in agreement with the potency order observed for guanine nucleotide-mediated inhibition of [35S]ADP beta S binding in purified turkey erythrocyte plasma membranes. The rate constant for dissociation of [35S]ADP beta S from solubilized Receptors was increased 2.3-fold by guanosine 59-O-(3-thiotriphosphate) (GTP gamma S). Plasma membrane P2Y-Purinergic Receptors were labeled with [35S]ADP beta S or covalently labeled with the photoaffinity probe 39-O-(4-benzoyl)benzoyl adenosine 59-[alpha-32P]triphosphate ([alpha-32P]BzATP) before solubilization and gel filtration chromatography on Superose 12. [35S]ADP beta S- or [alpha-32P]BzATP-labeled species eluted as a single peak of radioactivity of apparent Mr greater than or equal to 300,000. Incubation of the Mr greater than or equal to 300,000 protein species with GTP gamma S before rechromatography resulted in loss of labeling of proteins by [35S]ADP beta S and a shift in apparent size of the covalently [alpha-32P]BzATP-labeled species to a single peak of radioactivity of approximate Mr 70,000. These results suggest that a P2Y-Purinergic Receptor-guanine nucleotide regulatory protein complex is stable to membrane solubilization with digitonin, even in the absence of prebound agonist.
Nan Wang - One of the best experts on this subject based on the ideXlab platform.
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characterization of udp activated Purinergic Receptor p2y6 involved in japanese flounder paralichthys olivaceus innate immunity
International Journal of Molecular Sciences, 2018Co-Authors: Nan Wang, Gaixiang Hao, Jinsheng SunAbstract:Uridine 5’-diphosphate (UDP)-activated Purinergic Receptor P2Y6 is a member of a G-protein-coupled Purinergic Receptor family that plays an important role in mammalian innate immunity. However, the role of the P2Y6 Receptor (P2Y6R) in fish immunity has not been investigated. In this report, we characterized a P2Y6R gene from Japanese flounder (Paralichthys olivaceus) and examined its role in fish innate immunity. Sequence analysis reveals that the Japanese flounder P2Y6R protein is conserved and possesses four potential glycosylation sites. Quantitative real-time RT-PCR analysis shows that P2Y6R is broadly distributed in all examined Japanese flounder tissues with dominant expression in the liver. In addition, P2Y6R gene expression was up-regulated in head kidney macrophages (HKMs) upon lipopolysaccharides (LPS) and poly(I:C) stimulations but down-regulated by LPS challenge in peripheral blood leukocytes (PBLs). Furthermore, pharmacological inhibition of the endogenous P2Y6 Receptor activity by the potently selective P2Y6R antagonist, MRS 2578, greatly up-regulated pro-inflammatory cytokine interleukin (IL)-1β, IL-6 and TNF-α gene expression in PBL cells treated with UDP. Moreover, LPS- and poly(I:C)-induced gene expression of IL-1β and TNF-α in Japanese flounder PBL cells was attenuated significantly by inhibition of P2Y6R activity with antagonist MRS 2578. Collectively, we, for the first time, showed the involvement of functional Purinergic P2Y6R in fish innate immunity.
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Characterization of UDP-Activated Purinergic Receptor P2Y6 Involved in Japanese Flounder Paralichthys olivaceus Innate Immunity
MDPI AG, 2018Co-Authors: Nan Wang, Gaixiang Hao, Jinsheng SunAbstract:Uridine 5’-diphosphate (UDP)-activated Purinergic Receptor P2Y6 is a member of a G-protein-coupled Purinergic Receptor family that plays an important role in mammalian innate immunity. However, the role of the P2Y6 Receptor (P2Y6R) in fish immunity has not been investigated. In this report, we characterized a P2Y6R gene from Japanese flounder (Paralichthys olivaceus) and examined its role in fish innate immunity. Sequence analysis reveals that the Japanese flounder P2Y6R protein is conserved and possesses four potential glycosylation sites. Quantitative real-time RT-PCR analysis shows that P2Y6R is broadly distributed in all examined Japanese flounder tissues with dominant expression in the liver. In addition, P2Y6R gene expression was up-regulated in head kidney macrophages (HKMs) upon lipopolysaccharides (LPS) and poly(I:C) stimulations but down-regulated by LPS challenge in peripheral blood leukocytes (PBLs). Furthermore, pharmacological inhibition of the endogenous P2Y6 Receptor activity by the potently selective P2Y6R antagonist, MRS 2578, greatly up-regulated pro-inflammatory cytokine interleukin (IL)-1β, IL-6 and TNF-α gene expression in PBL cells treated with UDP. Moreover, LPS- and poly(I:C)-induced gene expression of IL-1β and TNF-α in Japanese flounder PBL cells was attenuated significantly by inhibition of P2Y6R activity with antagonist MRS 2578. Collectively, we, for the first time, showed the involvement of functional Purinergic P2Y6R in fish innate immunity
Noriko Aoi - One of the best experts on this subject based on the ideXlab platform.
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the Purinergic Receptor p2y g protein coupled 2 p2ry2 gene associated with essential hypertension in japanese men
Journal of Human Hypertension, 2010Co-Authors: Zhaoxia Wang, Tomohiro Nakayama, Naoyuki Sato, Yoichi Izumi, Yuji Kasamaki, Masakatsu Ohta, Masayoshi Soma, Noriko Aoi, Yukio OzawaAbstract:The Purinergic Receptor P2Y, G-protein coupled, 2 ( P2RY2 ) gene associated with essential hypertension in Japanese men
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Purinergic Receptor p2y g protein coupled 2 p2ry2 gene is associated with cerebral infarction in japanese subjects
Hypertension Research, 2009Co-Authors: Zhaoxia Wang, Tomohiro Nakayama, Naoyuki Sato, Yoichi Izumi, Yuji Kasamaki, Masakatsu Ohta, Masayoshi Soma, Mai Yamaguchi, Noriko AoiAbstract:G-protein-coupled Purinergic Receptor P2Y2 (P2RY2) has an important role in the process of atherosclerosis related to cerebral infarction (CI). The aim of this study was to investigate the relationship between the P2RY2 gene and CI through a haplotype-based case-control study, including the separate analysis of two gender groups. A total of 237 CI patients and two control groups (control 1, 254; control 2, 255) were genotyped for five single nucleotide polymorphisms (SNPs) in the human P2RY2 gene (rs4944831, rs1783596, rs4944832, rs4382936, rs10898909). Among women, the distribution of the dominant rs4944832 phenotype (GG vs. GA+AA) differed significantly between the CI patients and the control 1 group (P=0.043) and between the CI patients and the control 2 group (P=0.029). Logistic regression analysis showed that the GG genotype of rs4944832 was significantly more prevalent in the female CI patients than in the control 1 (P=0.021) and control 2 groups (P=0.005). For all subjects, the overall distribution of the haplotype established by rs1783596-rs4382936-rs10898909 was significantly different between the CI patients and the control 1 group (P=0.027). For all subjects, the frequency of the T-A-G haplotype (rs1783596-rs4382936-rs10898909) was also significantly higher (P=0.031), whereas the frequency of the T-C-G haplotype (rs1783596-rs4382936-rs10898909) was significantly lower (P=0.029) in the CI patients than in the control 1 group. The present results indicate that the T-A-G haplotype of the human P2RY2 gene is a susceptibility haplotype for CI in Japanese subjects, and that the GG genotype is a genetic marker for CI, particularly in Japanese women.
