Inhibition of protein phosphatases induces IGF-1-blocked neurotrophin-insensitive neuronal apoptosis

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Abstract

We have previously described the marine toxin okadaic acid (OKA) to be a potent neurotoxin for-cultured rat cerebellar neurons, Here we show that OKA-induced neurodegeneration involves the DNA fragmentation characteristic of apoptosis and is protein synthesis-dependent. DNA fragmentation and neurotoxicity correlated with inhibition of protein phosphatase (PP) 2A rather than PP1 activity. Neurotrophins NT-3 and BDNF failed to protect from OKA-induced apoptotic neurotoxicity that was, however, totally prevented by insulin-like growth factor-1. Neuronal death by OKA was significantly reduced by protein kinase C inhibitors and by the L-type calcium channel agonist Bay K8644, while it was potentiated by the reduction of free extracellular calcium concentrations.

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Fernández-Sánchez, M. T., García-Rodríguez, A., Díaz-Trelles, R., & Novelli, A. (1996). Inhibition of protein phosphatases induces IGF-1-blocked neurotrophin-insensitive neuronal apoptosis. FEBS Letters, 398(1), 106–112. https://doi.org/10.1016/S0014-5793(96)01192-1

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