Prosurvival role of JAK/STAT and Akt signaling pathways in MPP+-induced apoptosis in neurons
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- 作者：Felix Junyent ; Daniel Alvira ; Marc Yeste-Velasco ; Aurelio Vazquez de la Torre ; Carlos Beas-Zarate ; Francesc X. Sureda ; Jaume Folch ; Mercè ; Pallà ; s ; Antoni Camins ; Ester Verdaguer
- 关键词：MPP+ ; STAT3 ; Cerebellar granule cells ; Akt ; Apoptosis
- 刊名：Neurochemistry International
- 出版年：2010
- 出版时间：December 2010
- 年：2010
- 卷：57
- 期：7
- 页码：774-782
- 全文大小：780 K
文摘
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 μM) 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 μM) 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+.