title: The effect of diphtheria toxin on the cellular uptake and efflux of L-carnitine. Evidence for a protective effect of prednisolone.
abstract: Diphtheria toxin added to the incubation medium reduced the rate of uptake and increased the efflux of L-[3H]carnitine in an established cell line from human heart (CCL 27, Girardi human heart cells). This resulted in a decrease in the level of intracellular carnitine to about 55% of control after exposure to 10(-8) mol/l diphtheria toxin for 24 h. As expected, a decrease in protein synthesis was found to be caused by the toxin, and this inhibition seemed to a large extent to antedate the alterations in the transport processes. Measurement of the kinetic parameters for the mechanism of uptake of L-[3H]carnitine revealed a reduction in V with unaltered Km after exposure to the toxin. We therefore suggest that diphtheria toxin imposes its effect on carnitine transport by inhibiting the synthesis of carriers. Prednisolone in the medium along with the toxin opposed its effect both on the uptake and efflux mechanism, but not on the inhibition of protein synthesis. Still, the decline in the intracellular level of carnitine was prevented by the corticoid hormone. Such a decline, accompanied by accumulation of triacyglycerols, occurs during the course of a diphtheric myocarditis. It is possible that prednisolone, by counteracting the effects of diphtheria toxin on the carnitine transport processes, could be beneficial in the treatment of this condition.
mesh_terms: D001693:Biological Transport, Active / Q000187:drug effects; D002331:Carnitine / Q000378:metabolism*; D002460:Cell Line; D004167:Diphtheria Toxin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D011239:Prednisolone / Q000494:pharmacology*; D014176:Protein Biosynthesis
chemical_list: D004167:Diphtheria Toxin; D011239:Prednisolone; D002331:Carnitine