Neomycin inhibits mastoparan-induced lactate dehydrogenase release, ethidium bromide accumulation, and intracellular fluorescein depletion in MDCK cells.
Mechanisms of cell death induced by toxins probably involve one or more processes such as inhibition of protein synthesis and impairment of plasma membrane integrity leading to an increase in membrane permeability. Since one of the possible actions of mastoparan, a cationic tetradecapeptide from wasp venom, is to perturb membrane phospholipids resulting in an increase in membrane permeability, we studied the effect of chemically synthesized mastoparan on lactate dehydrogenase release (LDH), ethidium bromide and fluorescein accumulation in Madin-Darby Canine Kidney (MDCK) cultured cells. Our results demonstrated that mastoparan induced cytosolic LDH release, ethidium bromide accumulation and intracellular fluorescein depletion in MDCK cells. Neomycin, a polycationic aminoglycoside, interacts with anionic polyphosphoinositides at the plasma membrane. Since both mastoparan and neomycin are cationic peptides and react with the negatively charged membrane phospholipids, we studied the interaction of these two peptides on membrane permeability. Our results demonstrated that neomycin inhibited mastoparan-induced LDH release, ethidium bromide accumulation and intracellular fluorescein depletion.
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Department of Physiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
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D000818:Animals; D001514:Bee Venoms / Q000494:pharmacology*; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D004285:Dogs; D004996:Ethidium / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000166:cytology* / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D009355:Neomycin / Q000494:pharmacology*; D010455:Peptides; D014862:Wasp Venoms / Q000494:pharmacology*
D001514:Bee Venoms; D005452:Fluoresceins; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; C037500:mastoparan; D007770:L-Lactate Dehydrogenase; D004996:Ethidium; D009355:Neomycin