Prosurvival role of JAK/STAT and Akt signaling pathways in MPP+-induced apoptosis in neurons

Junyent, F.; Alvira, D.; Yeste-Velasco, M.; de la Torre, AV; Beas-Zarate C.; Sureda, FX; Folch, J; Pallas, M.; Camins, A; Verdaguer, E

Keywords: apoptosis, mpp+, akt, STAT3, Cerebellar granule cells


In the present study the role of JAK/STAT and Akt in apoptosis was evaluated in cerebellar granule cells after treatment with the mitochondrial toxin MPP+. Firstly, we evaluated the role of the prosurvival Akt pathway in MPP+-induced apoptosis and found that MPP+ rapidly reduced the phosphorylation of Akt at Ser473. Since PTEN is an upstream regulator of Akt, its inhibition with bpV(pic) (1-30 mu M) should activate Akt, however, it did not attenuate CGC cell death mediated by MPP+ but protected CGC from apoptosis mediated by S/K deprivation. We also demonstrated that after the treatment with the complex I inhibitor, the expression levels of STAT1 increased and the levels of STAT3 decreased at the time points tested (0.5-8 h). Meanwhile, pharmacological inhibition of the JAK/STAT pathway with AG490 (10-40 mu M) was neuroprotective, probably due to its antioxidant properties, the Jak2-inhibitor-II potentiated MPP+ neurotoxicity. Collectively, our data indicate that the treatment of CGC with the neurotoxin MPP+ decreased two prosurvival pathways: STAT3 and Akt. Meanwhile Akt activation, using a PTEN inhibitor, did not play a prominent role in neuroprotection; loss of STAT3 could be a signal pathway involved in neuroprotection against the Parkinsonian neurotoxin MPP+. (C) 2010 Elsevier Ltd. All rights reserved.

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Título según WOS: Prosurvival role of JAK/STAT and Akt signaling pathways in MPP+-induced apoptosis in neurons
Volumen: 57
Número: 7
Fecha de publicación: 2010
Página de inicio: 774
Página final: 782
Idioma: English


Notas: ISI