title: P8 deficiency increases cellular ROS and induces HO-1.
abstract: The gene p8 encodes for a small cytoprotective protein with no apparent enzymatic activity being proposed to act as co-transcription factor whose expression is increased during inflammation. Recent data from astrocytes demonstrates that p8 suppression leads to induction of heme oxygenase 1 (HO-1). Here, we assessed the cross-talk between p8 and HO-1 in mouse embryonic fibroblasts (MEF) observing an increased expression of HO-1 in p8-deficient (p8(-/-)) MEFs in non-treated and treated conditions. This effect was independent of the cell cycle. Our findings revealed that generation of reactive oxygen species (ROS) was higher in p8(-/-) MEFs. Mitochondria and NADPH oxidases were not the origin of ROS. This observation was not restricted to MEF as suppression of p8 gene transcription in MiaPaCa-2 cells also led to increased intracellular ROS. Additionally, p8 deficiency did not affect the Rac1 dependant NADPH oxidase complex. Our data shows that p8 deficiency increases ROS and subsequently the expression of anti-oxidative enzymes, such as HO-1, suggesting an involvement in the anti-oxidative defense. Moreover, we suggest that the severity of AP observed in p8(-/-) mice is induced by an impaired anti oxidative capacity of the pancreas, which is caused by increased generation of ROS.
authors.affiliation: Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Germany; Center for Sepsis Control & Care, Jena University Hospital, Jena, Germany; Center for Infectious Diseases and Infection Control, Jena University Hospital, Jena, Germany. Electronic address: sebastian.weis@med.uni-jena.de.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Weis
authors.affiliation: Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Bielow
authors.affiliation: Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Sommerer
authors.affiliation: Centre de Recherche en Cancérologie de Marseille (CRCM), INSERM U1068, CNRS UMR 7258, Aix-Marseille Université and Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, Marseille, France.
authors.forename: Juan
authors.initials: J
authors.lastname: Iovanna
authors.affiliation: Vect-Horus S.A.S., 13344 Marseille Cedex 15, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Malicet
authors.affiliation: Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Mössner
authors.affiliation: Division of Gastroenterology and Rheumatology, Department of Internal Medicine, Neurology and Dermatology, University Hospital Leipzig, Germany.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Hoffmeister
mesh_terms: D000818:Animals; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000172:deficiency*; D004622:Embryo, Mammalian / Q000378:metabolism* / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000172:deficiency*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; C491644:Nupr1 protein, mouse; D017382:Reactive Oxygen Species; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: HO-1; Mouse embryonic fibroblasts; Reactive oxygen species; p8