Neurochemistry international
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Both insulin and tau, promoting neuronal differentiation (neurite outgrowth, neuronal polarity, and myelination) and cell survival, are associated with neurodegenerative disease (e.g., Alzheimer's disease). The aim of this study was to explore relation between insulin-induced activation of insulin signal and expression of tau protein on neurite-like process outgrowth in adrenal chromaffin cells. Primary cultured bovine adrenal chromaffin cells were incubated with insulin to determine whether stimulant of insulin signal could affect tau expression and neurite-like process outgrowth. ⋯ Pulse-label followed by polyacrylamide gel electrophoresis revealed that insulin accelerated tau protein synthesis rate (t(1/2)) from 2.6 to 1.9h. Insulin did not change tau mRNA level. Taken together, these results suggest that insulin-induced activation of PI3K∼mTOR pathway up-regulated tau protein via acceleration of protein synthesis, on which insulin promoted neurite-like process outgrowth.
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Much evidence exists for the involvement of vesicular zinc in neurotransmission and cortical plasticity. Recent studies have reported that mice deficient in zinc transporter-3 protein (ZnT3) and thus, vesicular zinc, have significant behavioural and biochemical deficits. Here, we examined whether phenotypic differences existed in the barrel cortices of ZnT3 KO mice using functional proteomics and quantitative PCR. ⋯ The reduced expression of Nrtkb persisted with whisker plucking. These data demonstrate that fundamental changes in the expression of proteins and genes important in neurotransmission occur in the absence of vesicular zinc. Furthermore, the complement of experience-dependent changes were different between WT and KO mice, indicating that the lack of vesicular zinc affects the process of cortical plasticity.
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Comparative Study
PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP+-induced neuronal apoptosis.
Vascular endothelial growth factor (VEGF), a specific pro-angiogenic peptide, has shown neuroprotective effects in the Parkinson's disease (PD) models, but the underlying mechanisms remain elusive. In this study, the neuroprotective properties of VEGF on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced neurotoxicity in primary cerebellar granule neurons were investigated. Pretreatment of VEGF prevented MPP(+)-induced neuronal apoptosis in a concentration- and time-dependent manner. ⋯ Interestingly, VEGF and PD98059 (an ERK kinase inhibitor) play a synergistic role in protecting neurons from MPP(+)-induced toxicity. Collectively, these findings suggest that the PI3-K/Akt and ERK pathways activated by VEGF play opposite roles in MPP(+)-induced neuronal apoptosis. This finding offers not only a new and clinically significant modality as to how VEGF exerts its neuroprotective effects but also a novel therapeutic strategy for PD by differentially regulating PD-associated signaling pathways.