title: BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species.
abstract: Reactive oxygen species (ROS) play a critical role in the progression of mitochondria-related diseases. A novel insulin sensitizer drug candidate, BGP-15, has been shown to have protective effects in several oxidative stress-related diseases in animal and human studies. In this study, we investigated whether the protective effects of BGP-15 are predominantly via preserving mitochondrial integrity and reducing mitochondrial ROS production. BGP-15 was found to accumulate in the mitochondria, protect against ROS-induced mitochondrial depolarization and attenuate ROS-induced mitochondrial ROS production in a cell culture model, and also reduced ROS production predominantly at the complex I-III system in isolated mitochondria. At physiologically relevant concentrations, BGP-15 protected against hydrogen peroxide-induced cell death by reducing both apoptosis and necrosis. Additionally, it attenuated bacterial lipopolysaccharide (LPS)-induced collapse of mitochondrial membrane potential and ROS production in LPS-sensitive U-251 glioma cells, suggesting that BGP-15 may have a protective role in inflammatory diseases. However, BGP-15 did not have any antioxidant effects as shown by in vitro chemical and cell culture systems. These data suggest that BGP-15 could be a novel mitochondrial drug candidate for the prevention of ROS-related and inflammatory disease progression.
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Sumegi
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Katalin
authors.initials: K
authors.lastname: Fekete
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Csenge
authors.initials: C
authors.lastname: Antus
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Debreceni
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Eniko
authors.initials: E
authors.lastname: Hocsak
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.|MTA-PTE Nuclear-Mitochondrial Interactions Research Group, University of Pécs Medical School, Pécs, Hungary.|Szentagothai Research Centre, Pécs, Hungary.
authors.forename: Ferenc
authors.initials: F
authors.lastname: Gallyas
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.|MTA-PTE Nuclear-Mitochondrial Interactions Research Group, University of Pécs Medical School, Pécs, Hungary.|Szentagothai Research Centre, Pécs, Hungary.
authors.forename: Balazs
authors.initials: B
authors.lastname: Sumegi
authors.affiliation: Department of Biochemistry and Medical Chemistry, University of Pécs Medical School, Pécs, Hungary.
authors.forename: Aliz
authors.initials: A
authors.lastname: Szabo
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010091:Oximes / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D002232:Carbocyanines; D008070:Lipopolysaccharides; D010091:Oximes; D010880:Piperidines; D017382:Reactive Oxygen Species; D013481:Superoxides; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D006861:Hydrogen Peroxide; C405586:BGP 15