Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders

China

Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders

China
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Wang W.,Qingdao University | Wang W.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | Song N.,Qingdao University | Song N.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | And 7 more authors.
Annals of Translational Medicine | Year: 2015

We previously reported that acetylated and phosphorylated derivatives of porphyran extracted from Porphyra haitanensis exhibit antioxidant activity in cell-free system. The aim of the present study was to investigate the neuroprotective effects of porphyran and its derivatives on 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to measure cell viability. Changes in the mitochondrial transmembrane potential (ΔΨm) were measured by rhodamine123 using flow cytometry. The results showed that porphyran and its two derivatives, acetylated porphyran (AP) and phosphorylated porphyran (PP) (<1 mg/mL) alone did not have any toxic effects on MES23.5 cells. The cell viability decreased when cells were treated with 25 μmol/L 6-OHDA. Both AP and PP, rather than porphyran, significantly antagonized 25 μmol/L 6-OHDA-induced cytotoxicity. However, neither AP nor PP could antagonize 6-OHDA-induced mitochondrial transmembrane potential (ΔΨm) collapse. None of the three materials were effective on cell survival when cells were cotreated with 75 μmol/L 6-OHDA. These results suggest that two derivatives of porphyran, AP and PP, could antagonize the weak toxicity of 6-OHDA on MES23.5 dopaminergic cells, possessing minor neuroprotective effects independent of mitochondria restoration. © Annals of Translational Medicine.


Sun X.-C.,Qingdao University | Ren X.-F.,Qingdao University | Ren X.-F.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | Chen L.,Qingdao University | And 7 more authors.
Journal of Steroid Biochemistry and Molecular Biology | Year: 2016

Accumulating clinical and experimental evidence suggests that chronic neuroinflammation is associated with dopaminergic neuronal death in Parkinson's disease (PD). Ginsenoside Rg1, the most active components of ginseng, possesses a variety of biological effects on the central nervous system, cardiovascular system and immune system. The present study aimed to evaluate the protective effects of ginsenoside Rg1 on lipopolysaccharide (LPS)-induced microglia activation and dopaminergic neuronal degeneration in rat substantia nigra (SN) and its potential mechanisms. Treatment with Rg1 could ameliorate the apomorphine-induced rotational behavior in LPS-lesioned rats. GR antagonist RU486 partly abolished the protective effect of Rg1. Rg1 treatment significantly attenuated LPS-induced loss of tyrosin hydroxlase (TH) positive neurons in substantial nigra par compacta (SNpc) and decreased content of dopamine (DA) and its metabolites in striatum of the lesioned side. Meanwhile, Rg1 significantly inhibited LPS-induced microglial activation and production of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and nitric oxide (NO). These effects were abolished by co-treatment with RU486. In addition, Rg1 treatment significantly inhibited the LPS-induced phosphorylation of IκB, extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal protein kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK) in the lesioned side of substantial nigra. These effect could be also partly blocked by RU486. Taken together, these data indicate that Rg1 has protective effects on mesencephalic dopaminergic neurons from LPS-induced microglia inflammation. GR signaling pathway might be involved in the anti-inflammatory effect of Rg1. © 2015 Elsevier Ltd. All rights reserved.


Ju C.,Qingdao University | Ju C.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | Hou L.,Qingdao University | Hou L.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | And 8 more authors.
Neurochemical Research | Year: 2015

The purpose of the study was to investigate the protective effect and molecular mechanism of chondroitin sulfate (CS) against 6-hydroxydopamine (6-OHDA) induced toxicity in the human neuroblastoma cell line SH-SY5Y. The results showed that CS could protect SH-SY5Y cells against 6-OHDA-induced injury. The subsequent mechanism study showed that the anti-oxidation of CS may partly be mediated through inhibiting the intracellular reactive oxygen species overproduction, recovering the reduction of nuclear NF-E2-related factor-2 (Nrf2) expression and the reduction of antioxidants activity induced by 6-OHDA. Furthermore, CS pretreatment significantly attenuated 6-OHDA-induced cell apoptosis and nuclear condensation. 6-OHDA-induced dysfunctions, including the decrease of mitochondrial membrane potential (ΔΨm), increase of intracellular free Ca2+, imbalance of Bcl-2/Bax ratio, release of Cyt-c from the mitochondria and activation of caspase-3 and caspase-9 were attenuated by CS pretreatment, which demonstrated that CS suppressed 6-OHDA-induced apoptosis in SH-SY5Y cells possibly through mitochondria protection. These results suggest that CS exhibits anti-oxidation through the up-regulation of Nrf2 along with endogenous antioxidant, and reduces apoptosis via inhibiting the mitochondrial pathway to protect SH-SY5Y cells damaged by 6-OHDA. © 2015, Springer Science+Business Media New York.


Zhang H.-Y.,Qingdao University | Zhang H.-Y.,Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders | Zhang H.-Y.,Weifang Medical University | Song N.,Qingdao University | And 7 more authors.
Biochimica et Biophysica Acta - Molecular Cell Research | Year: 2014

Iron accumulation is observed in the substantia nigra of patients with Parkinson's disease. However, it is unknown whether neurotrophic factors, brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) participate in the modulation of neuronal iron metabolism. Here, we investigated the effects and underlying mechanisms of BDNF and GDNF on the iron influx process in primary cultured ventral mesencephalic neurons. 6-hydroxydopamine-induced enhanced ferrous iron influx via improper up-regulation of divalent metal transporter 1 with iron responsive element (DMT1. +. IRE) was consistently relieved by BDNF and GDNF. Both the mRNA and protein levels of DMT1. +. IRE were down-regulated by BDNF or GDNF treatment alone. We further demonstrated the involvement of iron regulatory protein 1 (IRP1) in BDNF- and GDNF-induced DMT1. +. IRE expression. Extracellular-regulated kinase 1/2 (ERK1/2) and Akt were activated and participated in these processes. Inhibition of ERK1/2 and Akt phosphorylation abolished the down-regulation of IRP1 and DMT1. +. IRE induced by BDNF and GDNF. Taken together, these results show that BDNF and GDNF ameliorate iron accumulation via the ERK/Akt pathway, followed by inhibition of IRP1 and DMT1. +. IRE expression, which may provide new targets for the neuroprotective effects of these neurotrophic factors. © 2014 Elsevier B.V.

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