Lei Wei

Sun Yat-Sen University of Medical Sciences, Shengcheng, Guangdong, China

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Publications (4)11.54 Total impact

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    ABSTRACT: Wnt1, initially described as a modulator of embryonic development, has recently been discovered to exert cytoprotective effects in cellular models of several diseases, including Parkinson's disease (PD). We, therefore, examined the neuroprotective effects of exogenous Wnt1 on dopaminergic SH-SY5Y cells treated with 6-hydroxydopamine (6-OHDA). Here, we show that 10-500 μM 6-OHDA treatment decreased cell viability and increased lactate dehydrogenase (LDH) leakage. SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h showed reduced Wnt/β-catenin activity, decreased mitochondrial transmembrane potential, elevated levels of reactive oxidative species (ROS) and phosphatidylserine (PS) extraversion, increased levels of Chop and Bip/GRP78 and reduced level of p-Akt (Ser473). In contrast, exogenous Wnt1 attenuated 6-OHDA-induced changes. These results suggest that activation of the Wnt/β-catenin pathway by exogenous Wnt1 protects against 6-OHDA-induced changes by restoring mitochondria and endoplasmic reticulum (ER) function.
    Journal of Molecular Neuroscience 10/2012; · 2.89 Impact Factor
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    ABSTRACT: Endoplasmic reticulum (ER) stress has been shown to be associated with the pathogenesis of neurodegenerative disorders including Parkinson's disease (PD). HtrA2/Omi, from its participation in protein quality control, is involved in ER stress. However, little is known about the relationship between HtrA2/Omi and ER stress in PD. Here, we explored the association of HtrA2/Omi and ER stress in a cell model of PD and found that the expression level of HtrA2/Omi decreased with ER stress induction in 6-OHDA-treated SH-SY5Y cells. Furthermore, silencing endogenous expression of HtrA2/Omi with siRNA resulted in aggregated ER stress and cell death. Taken together, our results show that HtrA2/Omi may exert a protective function in 6-OHDA-induced cell death by regulating ER stress-related proteins. This research offers some clues as why mutations in HtrA2/Omi lead to higher susceptibility in some PD patients.
    Journal of Molecular Neuroscience 01/2012; 47(1):120-7. · 2.89 Impact Factor
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    ABSTRACT: Immune disorders may play an important role in the pathogenesis of Parkinson's disease (PD). Recently, polymorphisms in the HLA-DR region have been found to be associated with sporadic PD in European ancestry populations. However, polymorphisms in the HLA complex are highly variable with ethnic and geographic origin. To explore the relationships between polymorphisms of the HLA-DR region and sporadic PD in Chinese Han population, we genotyped 567 sporadic PD patients and 746 healthy controls in two independent series for the HLA-DRB1 locus with Polymerase chain reaction-sequence based typing(PCR-SBT). The χ(2) test was used to evaluate the distribution of allele frequencies between the patients and healthy controls. The impact of HLA-DRB1 alleles on PD risk was estimated by unconditional logistic regression. We found a significant higher frequency of HLA-DRB1*0301 in sporadic PD patients than in healthy controls and a positive association, which was independent of onset age, between HLA-DRB1*0301 and PD risk. Conversely, a lower frequency of HLA-DRB1*0406 was found in sporadic PD patients than in healthy controls, with a negative association between HLA-DRB1*0406 and PD risk. Furthermore, a meta-analysis involving 195205 individuals was conducted to summarize the frequencies of these two alleles in populations from various ethnic regions, we found a higher frequency of HLA-DRB1*0301, but a lower frequency of HLA-DRB1*0406 in European ancestry populations than that in Asians, this was consistent with the higher prevalence of sporadic PD in European ancestry populations. Based on these results, we speculate that HLA-DRB1 alleles are associated with the susceptibility to sporadic PD in Chinese Han population, among them HLA-DRB1*0301 is a risk allele while the effect of HLA-DRB1*0406 deserves debate.
    PLoS ONE 01/2012; 7(11):e48594. · 3.73 Impact Factor
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    ABSTRACT: Glycogen synthase kinase 3 beta (GSK3β) plays a critical role in signal transductions concerning neuronal death. In the present study, we investigated the potential role of GSK3β in 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma cell line SH-SY5Y. We assessed the apoptotic proteins and the relative levels of pGSK3β (Ser9) and pGSK3β (Tyr216) to GSK3β in 6-OHDA-treated SH-SY5Y. Furthermore, we downregulated the expression of GSK3β by short hairpin RNA (shRNA) interference and compared the cell viability and expression of apoptotic proteins in knockdown group with those in control group under the treatment of 6-OHDA. We found that 6-OHDA increased the expression of caspase-3 and caspase-9 but not caspase-8. Additionally, 6-OHDA decreased the ratio of pGSK3β (Ser9)/GSK3β and increased the ratio of pGSK3β (Tyr216)/GSK3β. Moreover, 6-OHDA induced less cell viability loss and lower expression of caspase-9 and caspase-3 in GSK3β knockdown group compared with control. The present data indicate that 6-OHDA may induce apoptosis in SH-SY5Y via the intrinsic death pathway and GSK3β knockdown can partly attenuate 6-OHDA-induced neuronal death and apoptosis, suggesting that GSK3β may have the potential to serve as a therapeutic target for PD.
    Neuroscience Letters 10/2010; 487(1):41-6. · 2.03 Impact Factor

Publication Stats

12 Citations
11.54 Total Impact Points

Institutions

  • 2012
    • Sun Yat-Sen University of Medical Sciences
      • Department of Neurology
      Shengcheng, Guangdong, China
  • 2010
    • Sun Yat-Sen University
      Shengcheng, Guangdong, China