Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. Recent studies suggest that sulfated hetero-polysaccharides (UF) protect against developing PD. However, the detailed mechanisms of how UF suppress neuronal death have not been fully elucidated. We investigated the cytoprotective mechanisms of UF using human dopaminergic neuroblastoma SH-SY5Y cells as a PD model. UF prevented H2O2-induced apoptotic cell death in SH-SY5Y cells in a dose-dependent manner. An examination of the PI3K/Akt upstream pathway revealed that UF-pretreated cells showed a decreased relative density of Akt, PI3K, and TrkA, and increased the phosphorylation of Akt, PI3K, and NGF; the PI3K inhibitor, LY294002, partially prevented this effect. An examination of the PI3K/Akt downstream pathway revealed the increased expression of the apoptosis-associated markers Bax, p53, CytC, and GSK3β, and the decreased expression of Bcl-2 in UF-treated cells. UF-treated cells also exhibited decreased caspase-3, caspase-8, and caspase-9 activities, which induced cell apoptosis. Our results demonstrate that UF affect the PI3K/Akt pathway, as well as downstream signaling. Therefore, the UF-mediated activation of PI3K/Akt could provide a new potential therapeutic strategy for neurodegenerative diseases associated with oxidative injury. These findings contribute to a better understanding of the critical roles of UF in the treatment of PD.
Highlights
Parkinson’s disease (PD), the second most common neurogegenerative disease in the elderly, is pathologically characterized by the loss of dopaminergic neurons (DA) in the substantia nigra and in the striatum [1]
Our results demonstrate that UF affect the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway, as well as downstream signaling
We found that the mRNA expression of the key apoptosis-related genes group and that of PAkt and PPI3K significantly increased to 1.96 ± 0.38 and 1.86 ± 0.25 of the control
Summary
Parkinson’s disease (PD), the second most common neurogegenerative disease in the elderly, is pathologically characterized by the loss of dopaminergic neurons (DA) in the substantia nigra and in the striatum [1]. Research suggests that there are several factors such as apoptosis, oxidative stress, genetic factors, environmental factors, mitochondrial function defect, and ubiquitin proteasome system dysfunction, which may be related to the pathogenesis of PD [2,3,4,5,6]. Neuroprotection is a useful therapeutic strategy for PD; there are almost no such drugs in clinic for halting or retarding the degeneration of dopaminergic neurons. Much research has focused on a neuroprotective strategy, and several drugs have been proposed as candidate neuroprotective agents for PD [7,8]. Mar. Drugs 2017, 15, 110; doi:10.3390/md15040110 www.mdpi.com/journal/marinedrugs
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