title: (+)-Pentazocine reduces oxidative stress and apoptosis in microglia following hypoxia/reoxygenation injury.
abstract: Sigma-1 receptors (σ1R) are highly expressed in neurons as well as microglia and have been shown to modulate the inflammatory response in the central nervous system and thus may serve as possible target for neuroprotective strategies. The aim of the present study was to test the effect of (+)-pentazocine, a putative σ 1R agonist, in an in vitro model of microglia activation.
  
  
  
  Microglia (BV2 cells) was exposed (3h) to 1% oxygen and reoxygenation was allowed for 24h. Cells were treated with different concentrations (1, 10, 25 and 50μM) of (+)-pentazocine in the presence or absence of NE-100 (1μM), a well established σ1R antagonist. Cell viability and apoptosis were measured by cytofluorimetric analysis, whereas oxidative stress was evaluated by reduced glutathione (GSH) content and mitochondrial potential analysis.
  
  
  
  Our results showed that (+)-pentazocine was able to increase cell viability and restore mitochondrial potential at all concentrations whereas only 1 and 10μM were able to reduce significantly apoptotic cell death, to restore reduced glutathione intracellular content and prevent ERK1/2 phosphorylation. All these effects were abolished by concomitant treatment with NE-100.
  
  
  
  (+)-pentazocine exhibits significant dose dependent protective effects in our in vitro model of microglial activation thus suggesting that σ1R may represent a possible target for neuroprotection.
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95100 Catania, Italy.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Heiss
authors.affiliation: Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Vanella
authors.affiliation: Azienda Ospedaliera Universitaria Policlinico "G. Rodolico", University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Murabito
authors.affiliation: Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Orazio
authors.initials: O
authors.lastname: Prezzavento
authors.affiliation: Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Agostino
authors.initials: A
authors.lastname: Marrazzo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95100 Catania, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Castruccio Castracani
authors.affiliation: Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Ignazio
authors.initials: I
authors.lastname: Barbagallo
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95100 Catania, Italy.
authors.forename: Agata
authors.initials: A
authors.lastname: Zappalà
authors.affiliation: Department of Drug Sciences, University of Catania, V.le A. Doria 6, 95125 Catania, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Arena
authors.affiliation: Azienda Ospedaliera Universitaria Policlinico "G. Rodolico", University of Catania, Via S. Sofia 78, 95125 Catania, Italy.
authors.forename: Marinella
authors.initials: M
authors.lastname: Astuto
authors.affiliation: Department of Biopathology and Medical Biotechnologies (DIBIMED), Section of Anaesthesia, Analgesia, Intensive Care and Emergency, Paolo Giaccone University Hospital, University of Palermo, Via Del Vespro 38, 90100, Palermo, Italy.
authors.forename: Antonino
authors.initials: A
authors.lastname: Giarratano
authors.affiliation: Department of Biomedical and Biotechnological Sciences, University of Catania, Via S. Sofia 64, 95100 Catania, Italy; Euro-Mediterranean Institute of Science and Technology, Via Michele Miraglia, 20, 90100 Palermo, Italy. Electronic address: livolti@unict.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Li Volti
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism* / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism* / Q000502:physiology; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D010423:Pentazocine / Q000008:administration & dosage*; D010766:Phosphorylation; D017480:Receptors, sigma / Q000819:agonists*; D000097605:Sigma-1 Receptor
chemical_list: D017304:Annexin A5; D005978:Glutathione; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010423:Pentazocine; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor
keywords: (+)-Pentazocine; Microglia; Oxidative stress; Sigma receptors