title: Level of haem oxygenase does not obligatorily reflect the sensitivity of PC12 cells to an oxidative shock induced by glutathione depletion.
abstract: In order to investigate the function of haem oxygenase in neuronal cell death or survival, we have determined in PC12 cells whether induction of haem oxygenase mRNA and protein or inhibition of haem oxygenase activity may be able to modulate the cell response to an oxidative stress. Inhibition of glutathione biosynthesis by buthionine sulfoximine (BSO) has indeed been demonstrated, in this cell line, to decrease the intracellular content of glutathione and to trigger a gradual and programmed cell death. Inhibition of haem oxygenase by zinc protoporphyrin IX, a potent inhibitor of this enzyme, or by a recently described peptidic inhibitor, induced a significant decrease in the toxicity of BSO. This protective action was not due to an alteration in the metabolism of glutathione and was still observed when the protecting agent was added several hours after BSO treatment. Induction of haem oxygenase-1 mRNA and protein by either haemin or pyrrolidine dithiocarbamate was associated with no protection or a significant reduction in the toxicity of BSO respectively. Our results indicate that induction of haem oxygenase-1 is not obligatorily associated with an improved resistance towards oxidative stress and suggest that a byproduct of haem degradation may also become detrimental.
authors.affiliation: Centre National de la Recherche Scientifique Unité mixte de Recherche, Université de Caen, Caen, France.
authors.forename: Albertine
authors.initials: A
authors.lastname: Leon
authors.forename: Isabelle
authors.initials: I
authors.lastname: Le Foll
authors.forename: Christiane
authors.initials: C
authors.lastname: Charriault-Marlangue
authors.forename: Jérome
authors.initials: J
authors.lastname: Leprince
authors.forename: Hubert
authors.initials: H
authors.lastname: Vaudry
authors.forename: Cécilia
authors.initials: C
authors.lastname: Gabriel
authors.forename: Dominique
authors.initials: D
authors.lastname: Duval
mesh_terms: D000818:Animals; D001663:Bilirubin / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005978:Glutathione / Q000378:metabolism*; D006162:Guanylate Cyclase; D006419:Heme Oxygenase (Decyclizing) / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010069:Oxadiazoles / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D016716:PC12 Cells; D011759:Pyrrolidines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D000071756:Soluble Guanylyl Cyclase; D013859:Thiocarbamates / Q000494:pharmacology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D020536:Enzyme Activators; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010069:Oxadiazoles; D011759:Pyrrolidines; D011810:Quinoxalines; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D013859:Thiocarbamates; C020972:pyrrolidine dithiocarbamic acid; D019328:Buthionine Sulfoximine; D006427:Hemin; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D005978:Glutathione; D001663:Bilirubin