title: Cytotoxic Effects of Tropodithietic Acid on Mammalian Clonal Cell Lines of Neuronal and Glial Origin.
abstract: The marine metabolite tropodithietic acid (TDA), produced by several Roseobacter clade bacteria, is known for its broad antimicrobial activity. TDA is of interest not only as a probiotic in aquaculture, but also because it might be of use as an antibacterial agent in non-marine or non-aquatic environments, and thus the potentially cytotoxic influences on eukaryotic cells need to be evaluated. The present study was undertaken to investigate its effects on cells of the mammalian nervous system, i.e., neuronal N2a cells and OLN-93 cells as model systems for nerve cells and glia. The data show that in both cell lines TDA exerted morphological changes and cytotoxic effects at a concentration of 0.3-0.5 µg/mL (1.4-2.4 µM). Furthermore, TDA caused a breakdown of the mitochondrial membrane potential, the activation of extracellular signal-regulated kinases ERK1/2, and the induction of the small heat shock protein HSP32/HO-1, which is considered as a sensor of oxidative stress. The cytotoxic effects were accompanied by an increase in intracellular Ca(2+)-levels, the disturbance of the microtubule network, and the reorganization of the microfilament system. Hence, mammalian cells are a sensitive target for the action of TDA and react by the activation of a stress response resulting in cell death.
authors.affiliation: Aquatic Microbial Ecology Group, Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, Oldenburg 26129, Germany. heidi.wichmann@uni-oldenburg.de.
authors.forename: Heidi
authors.initials: H
authors.lastname: Wichmann
authors.affiliation: Biochemistry Group, Department of Neurosciences, University of Oldenburg, Oldenburg 26111, Germany. farina.vocke@uni-oldenburg.de.
authors.forename: Farina
authors.initials: F
authors.lastname: Vocke
authors.affiliation: Aquatic Microbial Ecology Group, Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, Oldenburg 26129, Germany. thorsten.brinkhoff@icbm.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brinkhoff
authors.affiliation: Aquatic Microbial Ecology Group, Institute for Chemistry and Biology of the Marine Environment (ICBM), University of Oldenburg, Oldenburg 26129, Germany. meinhard.simon@icbm.de.
authors.forename: Meinhard
authors.initials: M
authors.lastname: Simon
authors.affiliation: Molecular Neurobiology, Department of Neurosciences, University of Oldenburg, Oldenburg 26111, Germany. christiane.richter.landsberg@uni-oldenburg.de.
authors.forename: Christiane
authors.initials: C
authors.lastname: Richter-Landsberg
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002460:Cell Line; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D041904:Roseobacter / Q000378:metabolism; D013312:Stress, Physiological / Q000187:drug effects; D014334:Tropolone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000633:toxicity
chemical_list: C527336:tropodithietic acid; D014334:Tropolone; D002118:Calcium
keywords: MAP kinases; Roseobacter clade bacteria; cytoskeleton; mitochondria; nerve cells; oligodendrocytes; oxidative stress