|Celastrol Enhances Cell Viability and Inhibits Amyloid-beta Production Induced by Lipopolysaccharide In Vitro|
|Zhao, Yan1,2; Zhao, Hailin2; Lobo, Niyati2; Guo, Xiangyang1; Gentleman, Steve M.3; Ma, Daqing2|
|关键词||Alzheimer&Prime s Disease Amyloid-beta Celastrol Cell Signal Lipopolysaccharide Neuroinflammation|
|刊名||JOURNAL OF ALZHEIMERS DISEASE|
|WOS标题词||Science & Technology|
|研究领域[WOS]||Neurosciences & Neurology|
|关键词[WOS]||HEAT-SHOCK PROTEINS ; ALZHEIMERS-DISEASE ; ANTIINFLAMMATORY DRUGS ; GENE POLYMORPHISMS ; PRECURSOR PROTEIN ; APOPTOSIS ; ACCUMULATION ; PEPTIDE ; DEATH ; PHOSPHORYLATION|
Background: Neuroinflammation is a notable hallmark of Alzheimer′s disease pathogenesis and can markedly exacerbate amyloid pathology. Celastrol, a pentacyclic-triterpene, has been found to possess anti-inflammatory properties.
Objective: The purpose of this study was to characterize the effects of celastrol on cell viability and amyloid-(A) peptide production induced by lipopolysaccharide (LPS) administration in H4 human neuroglioma cells stably transfected to overexpress human full length APP (H4-APP). Methods: H4-APP cells were exposed to 1, 10, and 100nM of celastrol in the presence of 0.1 g/ ml or 100g/ ml of LPS for 24 hours. The effects of celastrol were determined using MTT cell viability assay, immunohistochemistry, western blot, and ELISA.
Results: Cell viability tests revealed that a dose-dependent death of H4-APP cells following administration of LPS. Moreover, celastrol significantly reduced (p < 0.05) cell death induced by LPS compared to LPS alone. Furthermore, the administration of celastrol was associated with a significant reduction in LPS-stimulated A production compared to LPS alone. Western blot and immunofluorescence analysis showed that exposure to celastrol increased HSP-70 and Bcl-2 expression but decreased NF.B activity, phosphorylated glycogen synthase kinase-3 (GSK-3) at tyrosine 216 and cyclooxygenase-2 (COX-2) expression, A accumulation together with a reduction of superoxide and hydrogen peroxide generation. HSP-70 siRNA abolished celastrol mediated cytoprotection.
Conclusion: This study demonstrates that celastrol reduced both LPS-induced cell death and A production in vitro through increasing HSP-70 and Bcl-2 expression and reducing NF.B, COX-2, and GSK-3 expression and oxidative stress.
|资助机构||Chinese Society of Anesthesiology, Beijing, China ; The Alzheimer&prime ; s Society/BUPA foundation, London, UK|
|作者单位||1.Peking Univ, Dept Anaesthesiol, Hosp 3, Beijing 100871, Peoples R China|
2.Univ London Imperial Coll Sci Technol & Med, Chelsea & Westminster Hosp, Dept Surg & Canc, Fac Med, London, England
3.Univ London Imperial Coll Sci Technol & Med, Dept Med, Neuropathol Unit, London, England
|Zhao, Yan,Zhao, Hailin,Lobo, Niyati,et al. Celastrol Enhances Cell Viability and Inhibits Amyloid-beta Production Induced by Lipopolysaccharide In Vitro[J]. JOURNAL OF ALZHEIMERS DISEASE,2014,41(3):835-844.|
|APA||Zhao, Yan,Zhao, Hailin,Lobo, Niyati,Guo, Xiangyang,Gentleman, Steve M.,&Ma, Daqing.(2014).Celastrol Enhances Cell Viability and Inhibits Amyloid-beta Production Induced by Lipopolysaccharide In Vitro.JOURNAL OF ALZHEIMERS DISEASE,41(3),835-844.|
|MLA||Zhao, Yan,et al."Celastrol Enhances Cell Viability and Inhibits Amyloid-beta Production Induced by Lipopolysaccharide In Vitro".JOURNAL OF ALZHEIMERS DISEASE 41.3(2014):835-844.|