摘要: Oxidative stress is a major cause of sporadic Parkinson's disease (PD). Here, we demonstrated that c-Abl plays an important role in oxidative stress-induced neuronal cell death. C-Abl, a nonreceptor tyrosine kinase, was activated in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced acute PD model. Conditional knockout of c-Abl in neurons or treatment of mice with STI571, a c-Abl family kinase inhibitor, reduced the loss of dopaminergic neurons and ameliorated the locomotive defects induced by short-term MPTP treatment. By combining the SILAC (stable isotope labeling with amino acids in cell culture) technique with other biochemical methods, we identified p38 alpha as a major substrate of c-Abl both in vitro and in vivo and c-Abl-mediated phosphorylation is critical for the dimerization of p38 alpha. Furthermore, p38 alpha inhibition mitigated the MPTP-induced loss of dopaminergic neurons. Taken together, these data suggested that c-Abl-p38 alpha signaling may represent a therapeutic target for PD.
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期刊:
CELL DEATH AND DIFFERENTIATION
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分类:
生物学
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生物物理学
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生物物理、生物化学与分子生物学
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引用:
ChinaXiv:201605.00748
(或此版本
ChinaXiv:201605.00748V1)
DOI:10.12074/201605.00748V1
CSTR:32003.36.ChinaXiv.201605.00748.V1
- 推荐引用方式:
Wu, R.,Chen, H.,Ma, J.,He, Q.,Yuan, Z.,Wu, R.,Ma, J.,He, Q.,Yuan, Z.,Chen, H.,Yuan, Z.,Huang, Q.,Li, M.,Huang, Q.,Li, M.,Liu, Q.,.(2016).c-Abl-p38 alpha signaling plays an important role in MPTP-induced neuronal death.CELL DEATH AND DIFFERENTIATION.[ChinaXiv:201605.00748]
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