title: The cytotoxic mechanism of karlotoxin 2 (KmTx 2) from Karlodinium veneficum (Dinophyceae).
abstract: This study demonstrates that the polyketide toxin karlotoxin 2 (KmTx 2) produced by Karlodinium veneficum, a dinoflagellate associated with fish kills in temperate estuaries world-wide, alters vertebrate cell membrane permeability. Microfluorimetric and electrophysiological measurements were used to determine that vertebrate cellular toxicity occurs through non-selective permeabilization of plasma membranes, leading to osmotic cell lysis. Previous studies showed that KmTx 2 is lethal to fish at naturally-occurring concentrations measured during fish kills, while sub-lethal doses severely damage gill epithelia. This study provides a mechanistic explanation for the association between K. veneficum blooms and fish kills that has long been observed in temperate estuaries worldwide.
authors.affiliation: University of Maryland Center for Environmental Science, Institute of Marine and Environmental Technology, 701 East Pratt Street, Suite 236, Baltimore, MD 21202, USA. Electronic address: jonathan.deeds@fda.hhs.gov.
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Deeds
authors.affiliation: University of Maryland, Baltimore, Center for Biomedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Robert E
authors.initials: RE
authors.lastname: Hoesch
authors.affiliation: University of Maryland Center for Environmental Science, Institute of Marine and Environmental Technology, 701 East Pratt Street, Suite 236, Baltimore, MD 21202, USA. Electronic address: place@umces.edu.
authors.forename: Allen R
authors.initials: AR
authors.lastname: Place
authors.affiliation: University of Maryland, Baltimore, Center for Biomedical Engineering and Technology and Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Joseph P Y
authors.initials: JP
authors.lastname: Kao
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability / Q000187:drug effects; D004141:Dinoflagellida / Q000737:chemistry / Q000502:physiology; D004912:Erythrocytes / Q000187:drug effects; D005399:Fishes; D008297:Male; D061065:Polyketides; D011714:Pyrans / Q000494:pharmacology* / Q000633:toxicity; D011817:Rabbits; D051381:Rats; D014874:Water Pollutants, Chemical / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D061065:Polyketides; D011714:Pyrans; D014874:Water Pollutants, Chemical; C550130:karlotoxin 2
keywords: Colloid osmotic lysis; Fish kills; Karlotoxin; Non-selective membrane permeability; Pore-forming toxin