Neuroprotective effects of pituitary adenylate cyclase-activating polypeptide (PACAP) in MPP+-induced alteration of translational control in Neuro-2a neuroblastoma cells.
نویسندگان
چکیده
UNLABELLED Parkinson's disease (PD) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity are both associated with dopaminergic neuron death in the substantia nigra. Although a variety of evidence has shown that degenerative cells have apoptotic features, the role of apoptosis in disease pathology remains controversial. The 1-methyl-4-phenylpyridinium ion (MPP(+)), a metabolite of MPTP, was recently shown to alter the expression of proteins involved in translational control. The initiation step of translational control is regulated by a cascade of phosphorylation affecting proteins of the antiapoptotic way controlled by mammalian target of rapamycin (mTOR) and of the proapoptotic way controlled by double-stranded RNA protein-dependent kinase (PKR). A study showed that MPP(+) induced an increase in eIF2alpha phosphorylation, leading to inhibition of protein synthesis. THE AIMS OF OUR STUDY WERE (1) to assess the effects of MPP(+) toxicity on molecular factors of PKR and mTOR signaling pathways in murine neuroblastoma cells, and (2) to examine the ability of VIP and PACAP peptides to counteract the MPP(+) toxicity. Our findings showed that MPP(+) induced phosphorylation of eIF2alpha and significantly reduced the expression of phosphorylated mTOR, p70S6K, eIF4E, and 4E-BP1, suggesting its toxicity in controlling protein synthesis. Furthermore, the VIP peptide had no effect on either the PKR or the mTOR signaling pathway. On the contrary, the PACAP 27 neuropeptide prevented MPP(+)-induced eIF2alpha phosphorylation and blocked MPP(+) toxicity in molecular factors of the mTOR pathway. And last, PACAP 27 seemed to protect Neuro-2a cells from the apoptotic process as assessed by the decreased nuclear condensation after DAPI staining. These results could open new paths of research of PACAP in PD.
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ورودعنوان ژورنال:
- Journal of neuroscience research
دوره 85 9 شماره
صفحات -
تاریخ انتشار 2007