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

Abstract:

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) (1-30μM) 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 (0.5-8h). Meanwhile, pharmacological inhibition of the JAK/STAT pathway with AG490 (10-40μM) 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 +. © 2010 Elsevier Ltd.

Año de publicación:

2010

Keywords:

• apoptosis
• MPP +
• Akt
• STAT3, Cerebellar granule cells

Fuente:

scopus