LIVIVO - Das Suchportal für Lebenswissenschaften

switch to English language
Zurück zur letzten Suche Suchhistorie
Erweiterte Suche

Ihre letzten Suchen

  1. AU="Cronin, Chunxia"
  2. AU=Weder W
  3. AU="Nirja Thakur"
  4. AU="Jiang, Shimin"
  5. AU="Wu, Xue-Ying"
  6. AU="Carlos Augusto de Mattos"
  7. AU="Procopio, Francesco A"
  8. AU="Nagata, Kosei"
  9. AU="Kevin Pottie"
  10. AU=Das Tandrila AU=Das Tandrila
  11. AU="Couto Souza, Paulo Henrique"
  12. AU="Morris, Zachary"

Suchergebnis

Treffer 1 - 10 von insgesamt 15

Suchoptionen

  1. Artikel: Transcriptomic analysis reveals novel age-independent immunomodulatory proteins as a mode of cerebroprotection in P2X4R KO mice after ischemic stroke.

    Gamiotea-Turro, Daylin / Cronin, Chunxia C / Liang, Bruce T / Verma, Rajkumar

    Research square

    2023  

    Abstract: Identification of new potential drug target proteins and their plausible mechanisms for stroke treatment is critically needed. We previously showed that genetic deletion and short-term pharmacological inhibition of P2X4R, a purinergic receptor for ... ...

    Abstract Identification of new potential drug target proteins and their plausible mechanisms for stroke treatment is critically needed. We previously showed that genetic deletion and short-term pharmacological inhibition of P2X4R, a purinergic receptor for adenosine triphosphate ATP, provides acute cerebroprotection. However, potential mechanisms remain unknown. Therefore, we employed RNA-seq technology to identify the gene expression profiles, pathway analysis, and qPCR validation of differentially expressed genes (DEGs). This analysis identified roles of DEGs in certain biological processes responsible for P2X4R-dependent cerebroprotection after stroke. We subjected both young and aged male and female global P2X4 KO and littermate WT mice to ischemic stroke. After 3 days, mice were sacrificed, total RNA was isolated using Trizol, and subjected to RNA-seq and Nanostring-mediated qPCR. DESeq2, Gene Ontology (GO), and Ingenuity Pathway Analysis (IPA) were used to identify mRNA transcript expression profiles and biological pathways. We found 2246 DEGs in P2X4R KO vs WT tissue after stroke. Out of these DEGs, 1920 gene were downregulated, and 325 genes were upregulated in KO. GO/IPA analysis of the top 300 DEGs suggests an enrichment of inflammation and extracellular matrix component genes. qPCR validation of the top 30 DEGs revealed downregulation of two common age-independent genes in P2X4R KO mice: Interleukin-6 (
    Sprache Englisch
    Erscheinungsdatum 2023-03-31
    Erscheinungsland United States
    Dokumenttyp Preprint
    DOI 10.21203/rs.3.rs-2747807/v1
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Fernleihe an ZB MED

    Sie können sich den gewünschten Titel als lokale Nutzerin oder lokaler Nutzer von ZB MED direkt an den Standort Köln schicken lassen.

  2. Artikel ; Online: Transcriptomic analysis reveals novel age-independent immunomodulatory proteins as a mode of cerebroprotection in P2X4 receptor knockout mice after ischemic stroke.

    Gamiotea-Turro, Daylin / Cronin, Chunxia C / Liang, Bruce T / Verma, Rajkumar

    Purinergic signalling

    2023  Band 19, Heft 3, Seite(n) 489–500

    Abstract: Identification of new potential drug target proteins and their plausible mechanisms for stroke treatment is critically needed. We previously showed that genetic deletion and short-term pharmacological inhibition of P2X4, a purinergic receptor for ... ...

    Abstract Identification of new potential drug target proteins and their plausible mechanisms for stroke treatment is critically needed. We previously showed that genetic deletion and short-term pharmacological inhibition of P2X4, a purinergic receptor for adenosine triphosphate (ATP), provides acute cerebroprotection. However, potential mechanisms remain unknown. Therefore, we employed RNA-Seq technology to identify the gene expression profiles and pathway analysis followed by qPCR validation of differentially expressed genes (DEGs). This analysis identified roles of DEGs in certain biological processes responsible for P2X4R-dependent cerebroprotection after stroke. We subjected both young and aged male and female global P2X4 receptor knock out (P2X4RKO) and littermate WT (WT) mice to ischemic stroke. After three days, mice were sacrificed, and total RNA was isolated using Trizol and subjected to RNA-Seq and NanoString-mediated qPCR. DESeq2, Gene Ontology (GO), and Ingenuity Pathway Analysis (IPA) were used to identify gene expression profiles and biological pathways. We found 2246 DEGs in P2X4R KO vs. WT tissue after stroke. Out of these DEGs, 1920 genes were downregulated and 325 genes were upregulated in P2X4R KO. GO/IPA analysis of the top 300 DEGs suggests an enrichment of inflammation and extracellular matrix component genes. qPCR validation of the top 30 DEGs revealed downregulation of two common age-independent genes in P2X4R KO mice: Interleukin-6 (Il-6), an inflammatory cytokine, and Cytotoxic T Lymphocyte-Associated Protein 2 alpha (Ctla2a), an immunosuppressive factor. These data suggest that P2X4R-mediated cerebroprotection after stroke is initiated by attenuation of immune modulatory pathways in both young and aged mice of both sexes.
    Mesh-Begriff(e) Mice ; Male ; Female ; Animals ; Ischemic Stroke ; Receptors, Purinergic P2X4/genetics ; Mice, Knockout ; Stroke/genetics ; Gene Expression Profiling
    Chemische Substanzen Receptors, Purinergic P2X4
    Sprache Englisch
    Erscheinungsdatum 2023-07-13
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 2172143-9
    ISSN 1573-9546 ; 1573-9538
    ISSN (online) 1573-9546
    ISSN 1573-9538
    DOI 10.1007/s11302-023-09956-9
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  3. Artikel ; Online: PLCβ2 Promotes VEGF-Induced Vascular Permeability.

    Phoenix, Kathryn N / Yue, Zhichao / Yue, Lixia / Cronin, Chunxia G / Liang, Bruce T / Hoeppner, Luke H / Claffey, Kevin P

    Arteriosclerosis, thrombosis, and vascular biology

    2022  Band 42, Heft 10, Seite(n) 1229–1241

    Abstract: Background: Regulation of vascular permeability is critical to maintaining tissue metabolic homeostasis. VEGF (vascular endothelial growth factor) is a key stimulus of vascular permeability in acute and chronic diseases including ischemia reperfusion ... ...

    Abstract Background: Regulation of vascular permeability is critical to maintaining tissue metabolic homeostasis. VEGF (vascular endothelial growth factor) is a key stimulus of vascular permeability in acute and chronic diseases including ischemia reperfusion injury, sepsis, and cancer. Identification of novel regulators of vascular permeability would allow for the development of effective targeted therapeutics for patients with unmet medical need.
    Methods: In vitro and in vivo models of VEGFA-induced vascular permeability, pathological permeability, quantitation of intracellular calcium release and cell entry, and phosphatidylinositol 4,5-bisphosphate levels were evaluated with and without modulation of PLC (phospholipase C) β2.
    Results: Global knock-out of
    Conclusions: The results implicate PLCβ2 as a key positive regulator of VEGF-induced vascular permeability through regulation of both calcium flux and phosphatidylinositol 4,5-bisphosphate levels at the cellular level. Targeting of PLCβ2 in a therapeutic setting may provide a novel approach to regulating vascular permeability in patients.
    Mesh-Begriff(e) Animals ; Calcium/metabolism ; Capillary Permeability/genetics ; Capillary Permeability/physiology ; Endothelial Cells/metabolism ; Humans ; Lung/metabolism ; Mice ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Phospholipase C beta/genetics ; Phospholipase C beta/metabolism ; Phospholipase C beta/physiology ; Respiratory Mucosa/metabolism ; Vascular Endothelial Growth Factor A
    Chemische Substanzen Phosphatidylinositol 4,5-Diphosphate ; Vascular Endothelial Growth Factor A ; PLCB2 protein, human (EC 3.1.4.11) ; Phospholipase C beta (EC 3.1.4.11) ; Plcb2 protein, mouse (EC 3.1.4.11) ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2022-07-21
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1221433-4
    ISSN 1524-4636 ; 1079-5642
    ISSN (online) 1524-4636
    ISSN 1079-5642
    DOI 10.1161/ATVBAHA.122.317645
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 1705: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  4. Artikel ; Online: Neuroprotective and neuro-rehabilitative effects of acute purinergic receptor P2X4 (P2X4R) blockade after ischemic stroke.

    Srivastava, Pranay / Cronin, Chunxia G / Scranton, Victoria L / Jacobson, Kenneth A / Liang, Bruce T / Verma, Rajkumar

    Experimental neurology

    2020  Band 329, Seite(n) 113308

    Abstract: Stroke remains a leading cause of disability in the United States. Despite recent advances, interventions to reduce damage and enhance recovery after stroke are lacking. P2X4R, a receptor for adenosine triphosphate (ATP), regulates activation of myeloid ... ...

    Abstract Stroke remains a leading cause of disability in the United States. Despite recent advances, interventions to reduce damage and enhance recovery after stroke are lacking. P2X4R, a receptor for adenosine triphosphate (ATP), regulates activation of myeloid immune cells (infiltrating monocytes/macrophages and brain-resident microglia) after stroke injury. However, over-stimulation of P2X4Rs due to excessive ATP release from dying or damaged neuronal cells can contribute to ischemic injury. Therefore, we pharmacologically inhibited P2X4R to limit the over-stimulated myeloid cell immune response and improve both acute and chronic stroke recovery. We subjected 8-12-week-old male and female wild type mice to a 60 min right middle cerebral artery occlusion (MCAo) followed by 3 or 30 days of reperfusion. We performed histological, RNA sequencing, behavioral (sensorimotor, anxiety, and depressive), and biochemical (Evans blue dye extravasation, western blot, quantitative PCR, and flow cytometry) analyses to determine the acute (3 days after MCAo) and chronic (30 days after MCAo) effects of P2X4R antagonist 5-BDBD (1 mg/kg P.O. daily x 3 days post 4 h of MCAo) treatment. 5-BDBD treatment significantly (p < .05) reduced infarct volume, neurological deficit (ND) score, levels of cytokine interleukin-1 beta (IL-1β) and blood brain barrier (BBB) permeability in the 3-day group. Chronically, 5-BDBD treatment also conferred progressive recovery (p < .05) of motor balance and coordination using a rotarod test, as well as reduced anxiety-like behavior over 30 days. Interestingly, depressive-type behavior was not observed in mice treated with 5-BDBD for 3 days. In addition, flow cytometric analysis revealed that 5-BDBD treatment decreased the total number of infiltrated leukocytes, and among those infiltrated leukocytes, pro-inflammatory cells of myeloid origin were specifically reduced. 5-BDBD treatment reduced the cell surface expression of P2X4R in flow cytometry-sorted monocytes and microglia without reducing the total P2X4R level in brain tissue. In summary, acute P2X4R inhibition protects against ischemic injury at both acute and chronic time-points after stroke. Reduced numbers of infiltrating pro-inflammatory myeloid cells, decreased surface P2X4R expression, and reduced BBB disruption are likely its mechanism of neuroprotection and neuro-rehabilitation.
    Mesh-Begriff(e) Animals ; Benzodiazepinones/pharmacology ; Benzodiazepinones/therapeutic use ; Dose-Response Relationship, Drug ; Female ; HEK293 Cells ; Humans ; Ischemic Stroke/metabolism ; Ischemic Stroke/prevention & control ; Ischemic Stroke/rehabilitation ; Male ; Mice ; Mice, Inbred C57BL ; Neuroprotection/drug effects ; Neuroprotection/physiology ; Neuroprotective Agents/pharmacology ; Neuroprotective Agents/therapeutic use ; Purinergic P2X Receptor Antagonists/pharmacology ; Purinergic P2X Receptor Antagonists/therapeutic use ; Receptors, Purinergic P2X4/metabolism
    Chemische Substanzen 5-(3-bromophenyl)-1,3-dihydro-2H-benzofuro(3,2-e)-1,4-diazepin-2-one ; Benzodiazepinones ; Neuroprotective Agents ; P2RX4 protein, human ; Purinergic P2X Receptor Antagonists ; Receptors, Purinergic P2X4
    Sprache Englisch
    Erscheinungsdatum 2020-04-11
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 207148-4
    ISSN 1090-2430 ; 0014-4886
    ISSN (online) 1090-2430
    ISSN 0014-4886
    DOI 10.1016/j.expneurol.2020.113308
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 184: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  5. Artikel ; Online: Alicyclic Ring Size Variation of 4-Phenyl-2-naphthoic Acid Derivatives as P2Y

    Wen, Zhiwei / Pramanik, Asmita / Lewicki, Sarah A / Jung, Young-Hwan / Gao, Zhan-Guo / Randle, John C R / Cronin, Chunxia / Chen, Zhoumou / Giancotti, Luigino A / Whitehead, Gregory S / Liang, Bruce T / Breton, Sylvie / Salvemini, Daniela / Cook, Donald N / Jacobson, Kenneth A

    Journal of medicinal chemistry

    2023  Band 66, Heft 13, Seite(n) 9076–9094

    Abstract: ... ...

    Abstract P2Y
    Mesh-Begriff(e) Mice ; Animals ; Receptors, Purinergic P2/metabolism ; Naphthalenes/pharmacology ; Naphthalenes/therapeutic use ; Uridine Diphosphate Glucose/metabolism
    Chemische Substanzen 2-naphthoic acid (QLG01V0W2L) ; Receptors, Purinergic P2 ; Naphthalenes ; Uridine Diphosphate Glucose (V50K1D7P4Y)
    Sprache Englisch
    Erscheinungsdatum 2023-06-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/acs.jmedchem.3c00664
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.B 151: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  6. Artikel ; Online: Nexinhib20 Inhibits Neutrophil Adhesion and β

    Liu, Wei / Cronin, Chunxia G / Cao, Ziming / Wang, Chengliang / Ruan, Jianbin / Pulikkot, Sunitha / Hall, Alexxus / Sun, Hao / Groisman, Alex / Chen, Yunfeng / Vella, Anthony T / Hu, Liang / Liang, Bruce T / Fan, Zhichao

    Journal of immunology (Baltimore, Md. : 1950)

    2022  Band 209, Heft 8, Seite(n) 1574–1585

    Abstract: Neutrophils are critical for mediating inflammatory responses. Inhibiting neutrophil recruitment is an attractive approach for preventing inflammatory injuries, including myocardial ischemia-reperfusion (I/R) injury, which exacerbates cardiomyocyte death ...

    Abstract Neutrophils are critical for mediating inflammatory responses. Inhibiting neutrophil recruitment is an attractive approach for preventing inflammatory injuries, including myocardial ischemia-reperfusion (I/R) injury, which exacerbates cardiomyocyte death after primary percutaneous coronary intervention in acute myocardial infarction. In this study, we found out that a neutrophil exocytosis inhibitor Nexinhib20 inhibits not only exocytosis but also neutrophil adhesion by limiting β
    Mesh-Begriff(e) Animals ; CD18 Antigens/metabolism ; Calcium/metabolism ; Cell Adhesion ; Guanosine ; Guanosine Triphosphate/metabolism ; Humans ; Interleukin-8/metabolism ; Mice ; Mice, Inbred C57BL ; Neutrophils/metabolism ; Polyphosphates ; rac1 GTP-Binding Protein/metabolism
    Chemische Substanzen CD18 Antigens ; Interleukin-8 ; Polyphosphates ; Guanosine (12133JR80S) ; Guanosine Triphosphate (86-01-1) ; rac1 GTP-Binding Protein (EC 3.6.5.2) ; triphosphoric acid (NU43IAG5BC) ; Calcium (SY7Q814VUP)
    Sprache Englisch
    Erscheinungsdatum 2022-09-07
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 3056-9
    ISSN 1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
    ISSN (online) 1550-6606
    ISSN 0022-1767 ; 1048-3233 ; 1047-7381
    DOI 10.4049/jimmunol.2101112
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Ud II Zs.37: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MG 28: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  7. Artikel ; Online: Prevention and rescue of cardiac dysfunction by methanocarba adenosine monophosphonate derivatives.

    Shen, Jian-Bing / Toti, Kiran S / Chakraborty, Saibal / Kumar, T Santhosh / Cronin, Chunxia / Liang, Bruce T / Jacobson, Kenneth A

    Purinergic signalling

    2020  Band 16, Heft 1, Seite(n) 61–72

    Abstract: Accumulating evidence supports a therapeutic role of purinergic signaling in cardiac diseases. Previously, efficacy of systemically infused MRS2339, a charged methanocarba derivative of 2-Cl-adenosine monophosphate, was demonstrated in animal models of ... ...

    Abstract Accumulating evidence supports a therapeutic role of purinergic signaling in cardiac diseases. Previously, efficacy of systemically infused MRS2339, a charged methanocarba derivative of 2-Cl-adenosine monophosphate, was demonstrated in animal models of heart failure. We now test the hypothesis that an uncharged adenine nucleoside phosphonate, suitable as an oral agent with a hydrolysis-resistant phospho moiety, can prevent the development of cardiac dysfunction in a post-infarction ischemic or pressure overload-induced heart failure model in mice. The diester-masked uncharged phosphonate MRS2978 was efficacious in preventing cardiac dysfunction with improved left ventricular (LV) fractional shortening when administered orally at the onset of ischemic or pressure overload-induced heart failure. MRS2925, the charged, unmasked MRS2978 analog, prevented heart dysfunction when infused subcutaneously but not by oral gavage. When administered orally or systemically, MRS2978 but not MRS2925 could also rescue established cardiac dysfunction in both ischemic and pressure overload heart failure models. The diester-masked phosphate MRS4074 was highly efficacious at preventing the development of dysfunction as well as in rescuing pressure overload-induced and ischemic heart failure. MRS2978 was orally bioavailable (57-75%) giving rise to MRS2925 as a minor metabolite in vivo, tested in rats. The data are consistent with a novel therapeutic role of adenine nucleoside phosphonates in systolic heart failure.
    Mesh-Begriff(e) Adenosine Monophosphate/chemical synthesis ; Adenosine Monophosphate/chemistry ; Adenosine Monophosphate/pharmacology ; Animals ; Heart Failure ; Mice ; Purinergic P2X Receptor Agonists/chemical synthesis ; Purinergic P2X Receptor Agonists/chemistry ; Purinergic P2X Receptor Agonists/pharmacology
    Chemische Substanzen Purinergic P2X Receptor Agonists ; Adenosine Monophosphate (415SHH325A)
    Sprache Englisch
    Erscheinungsdatum 2020-01-27
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2172143-9
    ISSN 1573-9546 ; 1573-9538
    ISSN (online) 1573-9546
    ISSN 1573-9538
    DOI 10.1007/s11302-020-09688-0
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  8. Artikel ; Online: Deletion of the P2X4 receptor is neuroprotective acutely, but induces a depressive phenotype during recovery from ischemic stroke.

    Verma, Rajkumar / Cronin, Chunxia G / Hudobenko, Jacob / Venna, Venugopal R / McCullough, Louise D / Liang, Bruce T

    Brain, behavior, and immunity

    2017  Band 66, Seite(n) 302–312

    Abstract: Introduction: Acute ischemic injury leads to severe neuronal loss. One of the key mechanisms responsible for this effect is inflammation, which is characterized by the activation of myeloid cells, including resident microglia and infiltrating monocytes/ ... ...

    Abstract Introduction: Acute ischemic injury leads to severe neuronal loss. One of the key mechanisms responsible for this effect is inflammation, which is characterized by the activation of myeloid cells, including resident microglia and infiltrating monocytes/macrophages. P2X4 receptors (P2X4Rs) present on these immune cells modulate the inflammatory response. For example, excessive release of adenosine triphosphate during acute ischemic stroke triggers stimulation of P2X4Rs, leading to myeloid cell activation and proliferation and further exacerbating post-ischemic inflammation. In contrast, during recovery P2X4Rs activation on microglia leads to the release of brain-derived neurotrophic factor (BDNF), which alleviate depression, maintain synaptic plasticity and hasten post-stroke behavioral recovery. Therefore, we hypothesized that deletion of the P2X4R specifically from myeloid cells would have differential effects on acute versus chronic recovery following stroke.
    Methods: We subjected global or myeloid-specific (MS) P2X4R knock-out (KO) mice and wild-type littermates of both sexes to right middle cerebral artery occlusion (60min). We performed histological, behavioral (sensorimotor and depressive), and biochemical (quantitative PCR and flow cytometry) analyses to determine the acute (three days after occlusion) and chronic (30days after occlusion) effects of receptor deletion.
    Results: Global P2X4R deletion led to reduced infarct size in both sexes. In MS P2X4R KO mice, only females showed reduced infarct size, an effect that did not change with ovariectomy. MS P2X4R KO mice of both sexes showed swift recovery from sensorimotor deficits during acute recovery but exhibited a more pronounced post-stroke depressive behavior phenotype that was independent of infarct size. Quantitative PCR analysis of whole cell lysate as well as flow-sorted myeloid cells from the perilesional cortex showed increased cellular interleukin 1 beta (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) mRNA levels but reduced plasma levels of these cytokines in MS P2X4R KO mice after stroke. The expression levels of BDNF and other depression-associated genes were reduced in MS P2X4R KO mice after stroke.
    Conclusions: P2X4R deletion protects against stroke acutely but predisposes to depression-like behavior chronically after stroke. Thus, a time-sensitive approach should be considered when targeting P2X4Rs after stroke.
    Mesh-Begriff(e) Animals ; Behavior, Animal ; Brain/metabolism ; Brain/pathology ; Brain Ischemia/complications ; Brain Ischemia/metabolism ; Brain Ischemia/pathology ; Cytokines/metabolism ; Depression/complications ; Depression/genetics ; Female ; Inflammation Mediators/metabolism ; Male ; Mice ; Mice, Knockout ; Microglia/pathology ; Phenotype ; RNA, Messenger/metabolism ; Receptors, Purinergic P2X4/genetics ; Receptors, Purinergic P2X4/metabolism ; Receptors, Purinergic P2X4/physiology ; Recovery of Function ; Stroke/complications ; Stroke/metabolism ; Stroke/pathology
    Chemische Substanzen Cytokines ; Inflammation Mediators ; RNA, Messenger ; Receptors, Purinergic P2X4
    Sprache Englisch
    Erscheinungsdatum 2017-07-24
    Erscheinungsland Netherlands
    Dokumenttyp Journal Article
    ZDB-ID 639219-2
    ISSN 1090-2139 ; 0889-1591
    ISSN (online) 1090-2139
    ISSN 0889-1591
    DOI 10.1016/j.bbi.2017.07.155
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Volltext online

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.A 2276: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)
    Zs.MO 327: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  9. Artikel ; Online: Elevated vascular endothelial growth factor receptor-2 abundance contributes to increased angiogenesis in vascular endothelial growth factor receptor-1-deficient mice.

    Ho, Vivienne C / Duan, Li-Juan / Cronin, Chunxia / Liang, Bruce T / Fong, Guo-Hua

    Circulation

    2012  Band 126, Heft 6, Seite(n) 741–752

    Abstract: Background: Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1) is a potential therapeutic target for cardiovascular diseases, but its role in angiogenesis remains controversial. Whereas germline Vegfr-1(-/-) embryos die of abnormal vascular ... ...

    Abstract Background: Vascular endothelial growth factor receptor-1 (VEGFR-1/Flt-1) is a potential therapeutic target for cardiovascular diseases, but its role in angiogenesis remains controversial. Whereas germline Vegfr-1(-/-) embryos die of abnormal vascular development in association with excessive endothelial differentiation, mice lacking only the kinase domain appear healthy.
    Methods and results: We performed Cre-loxP-mediated knockout to abrogate the expression of all known VEGFR-1 functional domains in neonatal and adult mice and analyzed developmental, pathophysiological, and molecular consequences. VEGFR-1 deficiency promoted tip cell formation and endothelial cell proliferation and facilitated angiogenesis of blood vessels that matured and perfused properly. Vascular permeability was normal at the basal level but elevated in response to high doses of exogenous VEGF-A. In the postinfarct ischemic cardiomyopathy model, VEGFR-1 deficiency supported robust angiogenesis and protected against myocardial infarction. VEGFR-1 knockout led to abundant accumulation of VEGFR-2 at the protein level, increased VEGFR-2 tyrosine phosphorylation transiently, and enhanced serine phosphorylation of Akt and ERK. Interestingly, increased angiogenesis, tip cell formation, vascular permeability, VEGFR-2 accumulation, and Akt phosphorylation could be partially rescued or suppressed by one or more of the following manipulations, including injection of the VEGFR-2 selective inhibitor SU1498, anti-VEGF-A, or introduction of Vegfr-2(+/-) heterozygosity into Vegfr-1 somatic knockout mice.
    Conclusions: Upregulation of VEGFR-2 abundance at the protein level contributes in part to increased angiogenesis in VEGFR-1-deficient mice.
    Mesh-Begriff(e) Animals ; Cardiomyopathies/genetics ; Cardiomyopathies/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neovascularization, Physiologic/genetics ; Up-Regulation/genetics ; Up-Regulation/physiology ; Vascular Endothelial Growth Factor Receptor-1/deficiency ; Vascular Endothelial Growth Factor Receptor-1/genetics ; Vascular Endothelial Growth Factor Receptor-2/biosynthesis ; Vascular Endothelial Growth Factor Receptor-2/genetics ; Vascular Endothelial Growth Factor Receptor-2/physiology
    Chemische Substanzen Vascular Endothelial Growth Factor Receptor-1 (EC 2.7.10.1) ; Vascular Endothelial Growth Factor Receptor-2 (EC 2.7.10.1)
    Sprache Englisch
    Erscheinungsdatum 2012-06-29
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80099-5
    ISSN 1524-4539 ; 0009-7322 ; 0069-4193 ; 0065-8499
    ISSN (online) 1524-4539
    ISSN 0009-7322 ; 0069-4193 ; 0065-8499
    DOI 10.1161/CIRCULATIONAHA.112.091603
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Ui IV Zs.60: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

  10. Artikel ; Online: 5'-Phosphate and 5'-phosphonate ester derivatives of (N)-methanocarba adenosine with in vivo cardioprotective activity.

    Kumar, T Santhosh / Yang, Tiehong / Mishra, Shilpi / Cronin, Chunxia / Chakraborty, Saibal / Shen, Jian-Bing / Liang, Bruce T / Jacobson, Kenneth A

    Journal of medicinal chemistry

    2013  Band 56, Heft 3, Seite(n) 902–914

    Abstract: Activation of a cardiac myocyte P2X4 receptor protects against heart failure. 5'-Phosphonate and 5'-phosphate analogues of AMP containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system could protect from heart failure by potentially activating this ... ...

    Abstract Activation of a cardiac myocyte P2X4 receptor protects against heart failure. 5'-Phosphonate and 5'-phosphate analogues of AMP containing a (N)-methanocarba (bicyclo[3.1.0]hexane) system could protect from heart failure by potentially activating this cardioprotective channel. Phosphoesters and phosphonodiesters were synthesized and administered in vivo via a miniosmotic pump in a mouse ischemic heart failure model and most significantly increased intact heart contractile function (echocardiography) compared to vehicle infusion. Several new thio and deuterated phosphate derivatives were protective in a calsequestrin (CSQ) overexpressing heart failure model. Diethyl (7, MRS4084) and diisopropyl (8, MRS4074) phosphotriesters were highly protective in the ischemic model. Substitution of 2-Cl with iodo reduced protection in the CSQ model. Diisopropyl ester 16 (MRS2978) of (1'S,2'R,3'S,4'R,5'S)-4'-(6-amino-2-chloropurin-9-yl)-2',3'-(dihydroxy)-1'-(phosphonoethylene)bicyclo[3.1.0]hexane was highly efficacious (CSQ), while lower homologue 1'-phosphonomethylene derivative 14 was inactive. Thus, we identified uncharged carbocyclic nucleotide analogues that represent potential candidates for the treatment of heart failure, suggesting this as a viable and structurally broad approach.
    Mesh-Begriff(e) Adenosine/analogs & derivatives ; Adenosine/chemistry ; Adenosine/pharmacology ; Animals ; Cardiotonic Agents/pharmacology ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Esters ; Magnetic Resonance Spectroscopy ; Mice ; Myocardial Ischemia/prevention & control ; Organophosphonates/chemistry ; Phosphates/chemistry ; Spectrometry, Mass, Electrospray Ionization
    Chemische Substanzen Cardiotonic Agents ; Esters ; Organophosphonates ; Phosphates ; Adenosine (K72T3FS567)
    Sprache Englisch
    Erscheinungsdatum 2013-01-22
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
    ZDB-ID 218133-2
    ISSN 1520-4804 ; 0022-2623
    ISSN (online) 1520-4804
    ISSN 0022-2623
    DOI 10.1021/jm301372c
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

    Zusatzmaterialien

    Kategorien

    Verfügbar in ZB MED Köln/Königswinter

    Zs.B 151: Hefte anzeigen Standort:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
    bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
    ab Jg. 2022: Lesesaal (EG)
    Zs.MB 1: Hefte anzeigen

    Über subito bestellen

    Dieser Service ist kostenpflichtig (siehe Lieferbedingungen von subito). Bestellungen, die einen Artikel nebst Supplementary Material umfassen, werden grundsätzlich wie mehrfache Bestellungen bearbeitet. Gebühren fallen in diesen Fällen für jede einzelne Bestellung an.

Zum Seitenanfang