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• W2013646403 startingPage "1541" @default.
• W2013646403 abstract "Fumonisin B1 (FB1), a potent and naturally occurring mycotoxin produced by the fungus Fusarium verticillioides, has been implicated in fatal and debilitating diseases in animals and humans. FB1 affects a variety of cell signaling proteins including protein kinase C (PKC); a serine/threonine kinase, involved in a number of signal transduction pathways that include cytokine induction, carcinogenesis and apoptosis. The aim of this study was to investigate the short-term temporal and concentration-dependent effects of FB1 on PKC isoforms present in LLC-PK1 cells in relation to the FB1-induced accumulation of sphinganine and sphingosine utilizing various inhibitors and activators. Our studies demonstrated that FB1 (0.1–1 μM) selectively and transiently activated PKCα at 5 min, without affecting PKC-δ, -ε and -ζ isoforms. At higher FB1 concentrations and later time points (15–120 min), PKCα membrane concentrations declined to untreated levels. The observed increase in cytosol PKCα protein expression at 15 min was not associated with an increase in its activity or protein biosynthesis. Calphostin C, a PKC inhibitor, abrogated the FB1-induced translocation of PKCα. Pre-incubation with the PKC activator, phorbol 12-myristate 13-acetate, resulted in an additive effect on membrane translocation of PKCα. Intracellular sphinganine and sphingosine concentrations were unaltered at the time points tested. Myriocin, a specific inhibitor of serine palmitoyltransferase, the first enzyme in de novo sphingolipid biosynthesis, did not prevent the FB1-induced PKCα cytosol to membrane redistribution. Altering PKCα and its signal transduction pathways may be of importance in the ability of FB1 to exert its toxicity via apoptosis and/or carcinogenesis." @default.
• W2013646403 created "2016-06-24" @default.
• W2013646403 creator A5001090733 @default.
• W2013646403 creator A5079763055 @default.
• W2013646403 date "2004-02-01" @default.
• W2013646403 modified "2023-10-16" @default.
• W2013646403 title "Selective and transient activation of protein kinase C α by fumonisin B1, a ceramide synthase inhibitor mycotoxin, in cultured porcine renal cells" @default.
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• W2013646403 doi "https://doi.org/10.1016/j.lfs.2003.08.022" @default.
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