title: The plant decapeptide OSIP108 prevents copper-induced toxicity in various models for Wilson disease.
abstract: BACKGROUND
  Wilson disease (WD) is caused by accumulation of excess copper (Cu) due to a mutation in the gene encoding the liver Cu transporter ATP7B, and is characterized by acute liver failure or cirrhosis and neuronal cell death. We investigated the effect of OSIP108, a plant derived decapeptide that prevents Cu-induced apoptosis in yeast and human cells, on Cu-induced toxicity in various mammalian in vitro models relevant for WD and in a Cu-toxicity zebrafish larvae model applicable to WD.
  
  
  METHODS
  The effect of OSIP108 was evaluated on viability of various cell lines in the presence of excess Cu, on liver morphology of a Cu-treated zebrafish larvae strain that expresses a fluorescent reporter in hepatocytes, and on oxidative stress levels in wild type AB zebrafish larvae.
  
  
  RESULTS
  OSIP108 increased not only viability of Cu-treated CHO cells transgenically expressing ATP7B and the common WD-causing mutant ATP7B(H1069Q), but also viability of Cu-treated human glioblastoma U87 cells. Aberrancies in liver morphology of Cu-treated zebrafish larvae were observed, which were further confirmed as Cu-induced hepatotoxicity by liver histology. Injections of OSIP108 into Cu-treated zebrafish larvae significantly increased the amount of larvae with normal liver morphology and decreased Cu-induced production of reactive oxygen species.
  
  
  CONCLUSIONS
  OSIP108 prevents Cu-induced toxicity in in vitro models and in a Cu-toxicity zebrafish larvae model applicable to WD.
  
  
  CONCLUSIONS
  All the above data indicate the potential of OSIP108 as a drug lead for further development as a novel WD treatment.
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium.
authors.forename: Pieter
authors.initials: P
authors.lastname: Spincemaille
authors.affiliation: Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O&N2, 3000 Leuven, Belgium.
authors.forename: Duc-Hung
authors.initials: DH
authors.lastname: Pham
authors.affiliation: Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster, Germany.
authors.forename: Gursimran
authors.initials: G
authors.lastname: Chandhok
authors.affiliation: Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Jef
authors.initials: J
authors.lastname: Verbeek
authors.affiliation: Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster, Germany.
authors.forename: Andree
authors.initials: A
authors.lastname: Zibert
authors.affiliation: Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium; Department of Pathology, University Hospital Ghent, De Pintelaan 185, 9000 Ghent, Belgium.
authors.forename: Louis
authors.initials: L
authors.lastname: Libbrecht
authors.affiliation: Clinic for Transplantation Medicine, Münster University Hospital, Albert-Schweitzer-Campus 1, Building A14, D-48149 Münster, Germany.
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.affiliation: Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O&N2, 3000 Leuven, Belgium.
authors.forename: Camila V
authors.initials: CV
authors.lastname: Esguerra
authors.affiliation: Laboratory for Molecular Biodiscovery, KU Leuven, Campus Gasthuisberg, Herestraat 49, O&N2, 3000 Leuven, Belgium.
authors.forename: Peter A M
authors.initials: PA
authors.lastname: de Witte
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium; Department of Plant Systems Biology, VIB, Technologiepark 927, 9052 Ghent, Belgium. Electronic address: bruno.cammue@biw.kuleuven.be.
authors.forename: Bruno P A
authors.initials: BP
authors.lastname: Cammue
authors.affiliation: Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: David
authors.initials: D
authors.lastname: Cassiman
authors.affiliation: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium.
authors.forename: Karin
authors.initials: K
authors.lastname: Thevissen
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics; D000818:Animals; D029681:Arabidopsis Proteins / Q000494:pharmacology*; D016466:CHO Cells; D027682:Cation Transport Proteins / Q000235:genetics; D045744:Cell Line, Tumor; D003300:Copper / Q000633:toxicity*; D000073840:Copper-Transporting ATPases; D003412:Cricetulus; D005909:Glioblastoma; D006527:Hepatolenticular Degeneration / Q000188:drug therapy*; D006801:Humans; D008099:Liver / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D015027:Zebrafish
chemical_list: D029681:Arabidopsis Proteins; D027682:Cation Transport Proteins; D009842:Oligopeptides; C000594979:methionyl-leucyl-cysteinyl-valyl-leucyl-glutaminyl-glycyl-leucyl-arginyl-glutamic acid; D003300:Copper; D000251:Adenosine Triphosphatases; C000612464:ATP7B protein, human; D000073840:Copper-Transporting ATPases
keywords: Copper; Hepatotoxicity; OSIP108; Wilson disease; Zebrafish