title: The plant decapeptide OSIP108 prevents copper-induced apoptosis in yeast and human cells.
abstract: We previously identified the Arabidopsis thaliana-derived decapeptide OSIP108, which increases tolerance of plants and yeast cells to oxidative stress. As excess copper (Cu) is known to induce oxidative stress and apoptosis, and is characteristic for the human pathology Wilson disease, we investigated the effect of OSIP108 on Cu-induced toxicity in yeast. We found that OSIP108 increased yeast viability in the presence of toxic Cu concentrations, and decreased the prevalence of Cu-induced apoptotic markers. Next, we translated these results to the human hepatoma HepG2 cell line, demonstrating anti-apoptotic activity of OSIP108 in this cell line. In addition, we found that OSIP108 did not affect intracellular Cu levels in HepG2 cells, but preserved HepG2 mitochondrial ultrastructure. As Cu is known to induce acid sphingomyelinase activity of HepG2 cells, we performed a sphingolipidomic analysis of OSIP108-treated HepG2 cells. We demonstrated that OSIP108 decreased the levels of several sphingoid bases and ceramide species. Moreover, exogenous addition of the sphingoid base dihydrosphingosine abolished the protective effect of OSIP108 against Cu-induced cell death in yeast. These findings indicate the potential of OSIP108 to prevent Cu-induced apoptosis, possibly via its effects on sphingolipid homeostasis.
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: 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 Medicine and the Stony Brook Cancer Center, University of Stony Brook, Stony Brook, New York, 11794, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Newcomb
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: Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Kasteelpark Arenberg 20, 3001 Heverlee, Belgium.
authors.forename: Kim
authors.initials: K
authors.lastname: Vriens
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: 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: Department of Medicine and the Stony Brook Cancer Center, University of Stony Brook, Stony Brook, New York, 11794, USA.
authors.forename: Yusuf A
authors.initials: YA
authors.lastname: Hannun
authors.affiliation: Department of Hepatology and Metabolic Center, University Hospital Gasthuisberg, Herestraat 49, 3000 Leuven, Belgium.
authors.forename: Jos
authors.initials: J
authors.lastname: van Pelt
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.|Department of Plant Systems Biology, VIB, Technologiepark 927, 9052, Ghent, Belgium.
authors.forename: Bruno P A
authors.initials: BPA
authors.lastname: Cammue
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: D017209:Apoptosis / Q000187:drug effects*; D017360:Arabidopsis / Q000378:metabolism*; D003300:Copper / Q000494:pharmacology*; D056945:Hep G2 Cells; D006801:Humans; D008854:Microscopy, Electron; D008928:Mitochondria / Q000187:drug effects / Q000648:ultrastructure; D009842:Oligopeptides / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000254:growth & development; D013107:Sphingolipids / Q000494:pharmacology*
chemical_list: D009842:Oligopeptides; D013107:Sphingolipids; D003300:Copper
keywords: Apoptosis; Ceramide; Copper; OSIP108; Saccharomyces cerevisiae