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

FEBS Letters
M Teresa Fernández-SánchezAntonello Novelli

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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Citations

Jul 23, 1999·Brain Research·M B Suárez-FernándezM T Fernández-Sánchez
Oct 31, 1998·Brain Research. Molecular Brain Research·V SolovyanA Salminen
Jun 2, 1998·Cellular Signalling·F J Gunn-Moore, J M Tavaré
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Jan 22, 2013·Toxicological Sciences : an Official Journal of the Society of Toxicology·Maria-Teresa Fernández-SánchezAntonello Novelli
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Mar 4, 2008·Free Radical Biology & Medicine·Amaia Ferrero-GutiérrezM Teresa Fernández-Sánchez
Dec 5, 2008·Journal of Neurochemistry·Kun Don YiJames W Simpkins
Jun 15, 2004·Neurobiology of Disease·Andrea M VincentEva L Feldman
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May 22, 2013·Neurotoxicology·Pradip K KamatChandishwar Nath
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Dec 3, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anabel Pérez-GómezM Teresa Fernández-Sánchez
Oct 14, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Anabel Pérez-GómezAntonello Novelli

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis