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

FEBS Letters

Díaz-Trelles, Ramón¹  Novelli, Antonello¹  Fernández-Sánchez, María-Teresa¹  García-Rodríguez, Armando¹ 

[1] Departamento de Bioquímica y Biología Molecular, Universidad de Oviedo, 33006 Oviedo, Spain

关键词: Okadaic acid;    Neurotoxicity;    Cerebellar neuron;    Calcium channel;    Protein kinase C;    Phosphorylation;   

DOI  :  10.1016/S0014-5793(96)01192-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown