title: Parkin modulates expression of HIF-1α and HIF-3α during hypoxia in gliobastoma-derived cell lines in vitro.
abstract: Mutation of the Parkin gene causes an autosomal recessive juvenile-onset form of Parkinson's disease. However, recently, it has been also linked to a wide variety of malignancies, including glioblastoma multiforme (GBM). In this pathology, Parkin exhibits a tumor suppressor role by mitigating the proliferation rate in both in vitro and in vivo models. However, Parkin involvement in the hypoxic process has not as yet been investigated. GBM is the most common and aggressive primary brain tumor in adults and is characterized by hypoxic areas. The low oxygen supply causes the expression of hypoxia-inducible factors (HIFs) leading to an accumulation of pro-angiogenic factors and tumoral invasiveness. We assess the relationship between Parkin and two HIFs expressed during hypoxic conditions, namely HIF-1α and HIF-3α. Our data show that Parkin is downregulated under hypoxia and that it interferes with HIF expression based on cellular oxygen tension. These results suggest a role for the involvement of Parkin in GBM, although further studies will be needed to understand the mechanism by which it modulates HIF-1α and HIF-3α expression.
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S.Sofia 87, 95123, Catania, Italy.
authors.forename: Grazia
authors.initials: G
authors.lastname: Maugeri
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S.Sofia 87, 95123, Catania, Italy.|San Raffaele Telematic University of Rome, Rome, Italy.
authors.forename: Agata Grazia
authors.initials: AG
authors.lastname: D'Amico
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S.Sofia 87, 95123, Catania, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Reitano
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Saccone
authors.affiliation: Section of Animal Biology, Department of Biological, Geological and Environmental Sciences, University of Catania, Catania, Italy.
authors.forename: Concetta
authors.initials: C
authors.lastname: Federico
authors.affiliation: Functional Genomics Unit, Institute of Neurological Sciences, Italian National Research Council, Catania, Italy.
authors.forename: Sebastiano
authors.initials: S
authors.lastname: Cavallaro
authors.affiliation: Sections of Human Anatomy and Histology, Department of Biomedical and Biotechnological Sciences, University of Catania, Via S.Sofia 87, 95123, Catania, Italy. vdagata@unict.it.
authors.forename: Velia
authors.initials: V
authors.lastname: D'Agata
mesh_terms: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism*; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012097:Repressor Proteins; D044767:Ubiquitin-Protein Ligases; C116973:HIF3A protein, human; C111567:parkin protein
keywords: Glioblastoma multiforme; HIF-1α; HIF-3α; Hypoxia; Parkin gene