title: Neuroglobin protects astroglial cells from hydrogen peroxide-induced oxidative stress and apoptotic cell death.
abstract: Oxidative stress, resulting from accumulation of reactive oxygen species, plays a critical role in astroglial cell death occurring in diverse neuropathological conditions. Numerous studies indicate that neuroglobin (Ngb) promotes neuron survival, but nothing is known regarding the action of Ngb in astroglial cell survival. Thus, the purpose of this study was to investigate the potential glioprotective effect of Ngb on hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis in cultured mouse astrocytes. Incubation of cells with subnanomolar concentrations of Ngb (10-14-10-10M) was found to prevent both H2O2-evoked reduction in surviving cells number and accumulation of reactive oxygen species in a concentration-dependent manner. Furthermore, Ngb treatment abolishes H2O2-induced increase in mitochondrial oxygen consumption rates. Concomitantly, Ngb treatment rescues H2O2-associated reduced expression of endogenous antioxidant enzymes (superoxide dismutases and catalase) and prevents the stimulation of the expression of pro-inflammatory genes (inducible nitric oxide synthase, cyclooxygenase-2, and interleukin (IL) IL-6 and IL-33). Moreover, Ngb blocks the stimulation of Bax (pro-apoptotic) and the inhibition of Bcl-2 (anti-apoptotic) gene expression induced by H2O2, which in turn abolishes caspase 3 activation. The protective effect of Ngb upon H2O2induced activation of caspase 3 activity and cell death can be accounted for by activation of protein kinase A and mitogen-activated protein kinase transduction cascade. Finally, we demonstrate that Ngb increases Akt phosphorylation and prevents H2O2-provoked inhibition of ERK and Akt phosphorylation. Taken together, these data demonstrate for the first time that Ngb is a glioprotective agent that prevents H2O2-induced oxidative stress and apoptotic astroglial cell death. Protection of astrocytes from oxidative insult may thus contribute to the neuroprotective effect of Ngb.
authors: Université de Tunis El Manar, Faculté des Sciences de Tunis, UR/11ES09 Laboratory of Functional Neurophysiology and Pathology, Tunisia.|Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR7258, Aix-Marseille Université UM105, Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors: Fatma
authors: F
authors: Amri
authors: Université de Tunis El Manar, Faculté des Sciences de Tunis, UR/11ES09 Laboratory of Functional Neurophysiology and Pathology, Tunisia.
authors: Ikram
authors: I
authors: Ghouili
authors: Université de Tunis El Manar, Faculté des Sciences de Tunis, UR/11ES09 Laboratory of Functional Neurophysiology and Pathology, Tunisia.
authors: Mohamed
authors: M
authors: Amri
authors: Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR7258, Aix-Marseille Université UM105, Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors: Alice
authors: A
authors: Carrier
authors: Université de Tunis El Manar, Faculté des Sciences de Tunis, UR/11ES09 Laboratory of Functional Neurophysiology and Pathology, Tunisia.
authors: Olfa
authors: O
authors: Masmoudi-Kouki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005914:Globins / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000633:toxicity*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D000078787:Neuroglobin; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology
chemical_list: D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D018696:Neuroprotective Agents; D005914:Globins; D006861:Hydrogen Peroxide
keywords: Neuroglobin; antioxidant enzymes; apoptosis; astroglial cells; pro-inflammatory genes; reactive oxygen species