Fumonisin B1-induced apoptosis is associated with delayed inhibition of protein kinase C, nuclear factor-κB and tumor necrosis factor α in LLC-PK1 cells

摘要: Abstract Fumonisin B1 (FB1), the most potent of fumonisin mycotoxins, is a carcinogen and causes wide range species-specific toxicoses. FB1 modulates activity protein kinase C (PKC), family phospholipid-dependent serine/threonine kinases that play important role in modulating variety biologic responses ranging from regulation cell growth to death. Although it has been demonstrated induces apoptosis many lines, precise mechanism not fully understood. In this study, we investigated membrane localization various PKC isoforms, enzyme activity, its downstream targets, namely nuclear factor-kappa B (NF-κB), tumor necrosis factor α (TNFα), caspase 3, porcine renal epithelial (LLC-PK1) cells. repressed cytosol translocation PKC-α, -δ, -e, -ζ isoforms over 24–72 h. The FB1-induced repression was corroborated by concentration-dependent decrease total activity. Exposure cells phorbol 12-myristate 13-acetate (PMA) for duration also resulted comparable FB1. (10 μM) associated with inhibition NF-κB NF-κB-DNA binding at 72 expression TNFα significantly inhibited 24 48 h response 1 10 μM Increased 3 observed LLC-PK1 exposed ≥1 PMA increased Results suggest involves activation which possibly down-stream effectors, TNFα.