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  1. AU="Leal Denis, M Florencia"
  2. AU=Wheeler Deric L AU=Wheeler Deric L
  3. AU="Prabhu S. Arunachalam"
  4. AU="Crețu, Oana Iulia"
  5. AU="Kim, Y G"
  6. AU=Lejuste Florian
  7. AU="Xavier-Carvalho, Caroline"
  8. AU="Lamb, Keith"
  9. AU="Şenbabaoğlu, Yasin"
  10. AU="Papaparaskeva, Kleo" AU="Papaparaskeva, Kleo"
  11. AU="Hanmer, Stuart B"
  12. AU="de Graaf, Gimon"
  13. AU=Bryan Nathan S
  14. AU="Bhatia, Chitra"
  15. AU="Neufeld, Niko"
  16. AU="Martínez-Cruz, Nayeli"
  17. AU="Joffe, Marshall M"
  18. AU="Wilunda, Calistus"
  19. AU="Das, Partha Pratim"
  20. AU="Staiano, Leopoldo"
  21. AU="Tibbatts, Clare"
  22. AU="Bandeira, Igor D"
  23. AU="Papathanassiou, Dimitri"
  24. AU="Mazurek, Camille"
  25. AU="Jenkinson, Crispin"
  26. AU="Hernández-Huérfano, Emilio Ernesto"
  27. AU="Conowall, Peter"
  28. AU="Nesan, Daniel"
  29. AU="Ueda, Takashi"
  30. AU="Yuan, Jiacheng"
  31. AU="Kahama, C B"
  32. AU="D’Alessio, Roberto"
  33. AU="Reuhl, Kenneth"
  34. AU="Seeleman, Conny"
  35. AU="Delaquis, Pascal"
  36. AU="Bommineni, Gopal R"
  37. AU="Kuhn, Cynthia M."
  38. AU="Olson, Jason C"
  39. AU="Buchholz, V."
  40. AU="Urquhart, Bradley L"
  41. AU="Ezaki, Kazune"
  42. AU="Choi, Jong Hyun"
  43. AU="Xie, Qiaowei"
  44. AU=Rojas-Marte G AU=Rojas-Marte G
  45. AU="Belli, A"
  46. AU="Moolman, M Charl"
  47. AU="Mazzoni, Stefania"
  48. AU=Stryjewski Martin E
  49. AU=Vallon Volker AU=Vallon Volker
  50. AU="Knowland, K E"
  51. AU="Beker, M. G."

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  1. Artikel ; Online: ShlA toxin of Serratia induces P2Y2- and α5β1-dependent autophagy and bacterial clearance from host cells.

    Tuttobene, Marisel R / Schachter, Julieta / Álvarez, Cora L / Saffioti, Nicolás A / Leal Denis, M Florencia / Kessler, Horst / García Véscovi, Eleonora / Schwarzbaum, Pablo J

    The Journal of biological chemistry

    2023  Band 299, Heft 9, Seite(n) 105119

    Abstract: Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely ... ...

    Abstract Serratia marcescens is an opportunistic human pathogen involved in antibiotic-resistant hospital acquired infections. Upon contact with the host epithelial cell and prior to internalization, Serratia induces an early autophagic response that is entirely dependent on the ShlA toxin. Once Serratia invades the eukaryotic cell and multiples inside an intracellular vacuole, ShlA expression also promotes an exocytic event that allows bacterial egress from the host cell without compromising its integrity. Several toxins, including ShlA, were shown to induce ATP efflux from eukaryotic cells. Here, we demonstrate that ShlA triggered a nonlytic release of ATP from Chinese hamster ovary (CHO) cells. Enzymatic removal of accumulated extracellular ATP (eATP) or pharmacological blockage of the eATP-P2Y2 purinergic receptor inhibited the ShlA-promoted autophagic response in CHO cells. Despite the intrinsic ecto-ATPase activity of CHO cells, the effective concentration and kinetic profile of eATP was consistent with the established affinity of the P2Y2 receptor and the known kinetics of autophagy induction. Moreover, eATP removal or P2Y2 receptor inhibition also suppressed the ShlA-induced exocytic expulsion of the bacteria from the host cell. Blocking α5β1 integrin highly inhibited ShlA-dependent autophagy, a result consistent with α5β1 transactivation by the P2Y2 receptor. In sum, eATP operates as the key signaling molecule that allows the eukaryotic cell to detect the challenge imposed by the contact with the ShlA toxin. Stimulation of P2Y2-dependent pathways evokes the activation of a defensive response to counteract cell damage and promotes the nonlytic clearance of the pathogen from the infected cell.
    Mesh-Begriff(e) Animals ; Cricetinae ; Adenosine Triphosphate/metabolism ; Autophagy/drug effects ; CHO Cells ; Cricetulus ; Exocytosis/drug effects ; Host-Pathogen Interactions/drug effects ; Integrin alpha5beta1/antagonists & inhibitors ; Integrin alpha5beta1/metabolism ; Receptors, Purinergic P2Y2/metabolism ; Serratia/chemistry ; Serratia/drug effects ; Serratia/physiology ; Toxins, Biological/pharmacology ; Humans
    Chemische Substanzen Adenosine Triphosphate (8L70Q75FXE) ; CD39 antigen (EC 3.6.1.5) ; Integrin alpha5beta1 ; Receptors, Purinergic P2Y2 ; Toxins, Biological
    Sprache Englisch
    Erscheinungsdatum 2023-07-30
    Erscheinungsland United States
    Dokumenttyp Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2997-x
    ISSN 1083-351X ; 0021-9258
    ISSN (online) 1083-351X
    ISSN 0021-9258
    DOI 10.1016/j.jbc.2023.105119
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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  2. Artikel ; Online: Dynamic Regulation of Cell Volume and Extracellular ATP of Human Erythrocytes.

    Leal Denis, M Florencia / Alvarez, H Ariel / Lauri, Natalia / Alvarez, Cora L / Chara, Osvaldo / Schwarzbaum, Pablo J

    PloS one

    2016  Band 11, Heft 6, Seite(n) e0158305

    Abstract: Introduction: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect ... ...

    Abstract Introduction: The peptide mastoparan 7 (MST7) triggered in human erythrocytes (rbcs) the release of ATP and swelling. Since swelling is a well-known inducer of ATP release, and extracellular (ATPe), interacting with P (purinergic) receptors, can affect cell volume (Vr), we explored the dynamic regulation between Vr and ATPe.
    Methods and treatments: We made a quantitative assessment of MST7-dependent kinetics of Vr and of [ATPe], both in the absence and presence of blockers of ATP efflux, swelling and P receptors.
    Results: In rbcs 10 μM MST7 promoted acute, strongly correlated changes in [ATPe] and Vr. Whereas MST7 induced increases of 10% in Vr and 190 nM in [ATPe], blocking swelling in a hyperosmotic medium + MST7 reduced [ATPe] by 40%. Pre-incubation of rbcs with 10 μM of either carbenoxolone or probenecid, two inhibitors of the ATP conduit pannexin 1, reduced [ATPe] by 40-50% and swelling by 40-60%, while in the presence of 80 U/mL apyrase, an ATPe scavenger, cell swelling was prevented. While exposure to 10 μM NF110, a blocker of ATP-P2X receptors mediating sodium influx, reduced [ATPe] by 48%, and swelling by 80%, incubation of cells in sodium free medium reduced swelling by 92%.
    Analysis and discussion: Results were analyzed by means of a mathematical model where ATPe kinetics and Vr kinetics were mutually regulated. Model dependent fit to experimental data showed that, upon MST7 exposure, ATP efflux required a fast 1960-fold increase of ATP permeability, mediated by two kinetically different conduits, both of which were activated by swelling and inactivated by time. Both experimental and theoretical results suggest that, following MST7 exposure, ATP is released via two conduits, one of which is mediated by pannexin 1. The accumulated ATPe activates P2X receptors, followed by sodium influx, resulting in cell swelling, which in turn further activates ATP release. Thus swelling and P2X receptors constitute essential components of a positive feedback loop underlying ATP-induced ATP release of rbcs.
    Mesh-Begriff(e) Adenosine Triphosphate/physiology ; Cell Size ; Culture Media ; Erythrocytes/drug effects ; Erythrocytes/metabolism ; Hemolysis ; Humans ; Kinetics ; Peptides/metabolism ; Receptors, Purinergic/metabolism ; Signal Transduction ; Sodium/metabolism
    Chemische Substanzen Culture Media ; Mas7 protein, synthetic ; Peptides ; Receptors, Purinergic ; Adenosine Triphosphate (8L70Q75FXE) ; Sodium (9NEZ333N27)
    Sprache Englisch
    Erscheinungsdatum 2016
    Erscheinungsland United States
    Dokumenttyp Journal Article
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0158305
    Datenquelle MEDical Literature Analysis and Retrieval System OnLINE

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