title: Decreased expression of the augmenter of liver regeneration results in increased apoptosis and oxidative damage in human-derived glioma cells.
abstract: The mammalian growth factor erv1-like (GFER) gene encodes a sulfhydryl oxidase enzyme, named Augmenter of Liver Regeneration (ALR). Recently it has been demonstrated that ALR supports cell proliferation acting as an anti-apoptotic factor. This effect is determined by ALR ability to support the anti-apoptotic gene expression and to preserve cellular normoxic conditions. We recently demonstrated that the addition of recombinant ALR (rALR) in the culture medium of H(2)O(2)-treated neuroblastoma cells reduces the lethal effects induced by the hydrogen peroxide. Similar data have been reported in the regenerating liver tissue from partially hepatectomized rats treated with rALR. The purpose of the present study was to evaluate the effect of the GFER inhibition, via the degradation of the complementary mRNA by the specific siRNA, on the behaviour of the apoptosis (apoptotic gene and caspase expression and apoptotic cell number) and of the oxidative stress-induced parameters (reactive oxygen species (ROS), clusterin expression and mitochondrial integrity) in T98G glioma cells. The results revealed a reduction of (i) ALR, (ii) clusterin and (iii) bcl-2 and an increase of (iv) caspase-9, activated caspase-3, ROS, apoptotic cell number and mitochondrial degeneration. These data confirm the anti-apoptotic role of ALR and its anti-oxidative properties, and shed some light on the molecular pathways through which ALR modulates its biological effects.
authors.affiliation: Section of Gastroenterology, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy. l.polimeno@gastro.uniba.it
authors.forename: L
authors.initials: L
authors.lastname: Polimeno
authors.forename: B
authors.initials: B
authors.lastname: Pesetti
authors.forename: F
authors.initials: F
authors.lastname: De Santis
authors.forename: L
authors.initials: L
authors.lastname: Resta
authors.forename: R
authors.initials: R
authors.lastname: Rossi
authors.forename: A
authors.initials: A
authors.lastname: De Palma
authors.forename: B
authors.initials: B
authors.lastname: Girardi
authors.forename: A
authors.initials: A
authors.lastname: Amoruso
authors.forename: A
authors.initials: A
authors.lastname: Francavilla
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D051152:Clusterin / Q000378:metabolism; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005786:Gene Expression Regulation; D005910:Glioma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D050862:Oxidoreductases Acting on Sulfur Group Donors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D051152:Clusterin; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D003579:Cytochrome Reductases; C500897:GFER protein, human; D050862:Oxidoreductases Acting on Sulfur Group Donors; D053148:Caspase 3; D053453:Caspase 9