title: The protective effects of tanshinone IIA on neurotoxicity induced by β-amyloid protein through calpain and the p35/Cdk5 pathway in primary cortical neurons.
abstract: The characteristic pathological change of Alzheimer's disease (AD) include deposits of β-amyloid protein (Aβ) in brain, neurofibrillary tangles (NFTs), as well as a few neuronal loss. Evidence shows that Aβ causes calcium influx and induces the cleavage of p35 into p25. Furthermore, the binding of p25 to cyclin-dependent kinase 5 (Cdk5) constitutively activates Cdk5. The p25/Cdk5 complex then hyperphosphorylates tau. Tanshinone IIA (tanIIA), a natural product extracted from Chinese herbal medicine Salvia miltiorrhiza BUNGE, has been reported to exert antioxidative activity. However, its neuroprotective activity remains unclear. The present study determined whether tanIIA protects neurons against Aβ(25-35)-induced cytotoxicity and detected the association of this protective effect with calpain and the p35/Cdk5 pathway. The results showed that tanIIA protected neurons against the neurotoxicity of Aβ(25-35), increased the viability of neurons, decreased expression of phosphorylated tau in neurons induced by Aβ(25-35), improved the impairment of the cell ultrastructure (such as nuclear condensation and fragmentation, and neurofibril collapse). Further more, we found that tanIIA maintained the normal expression of p35 on peripheral membranes, and decreased p25 expression in the cytoplasm. TanIIA also inhibited the translocation of Cdk5 from the nucleus into the cytoplasm of primary neurons induced by Aβ(25-35). These data suggested that tanIIA possessed neuroprotective action and the protection may involve in calpain and the p35/Cdk5 pathway.
authors.affiliation: Department of Human Anatomy and Histology Embryology, Institute of Neurobiology, Key Laboratory of Environment and Genes Related to Diseases of Education Ministry, Xi'an Jiaotong University College of Medicine, 76, Yanta West Road, Xi'an 710061, Shaanxi, China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shi
authors.forename: Wei-Na
authors.initials: WN
authors.lastname: Yang
authors.forename: Xin-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Jian-Shui
authors.initials: JS
authors.lastname: Zhang
authors.forename: Peng-Bo
authors.initials: PB
authors.lastname: Yang
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Hu
authors.forename: Hua
authors.initials: H
authors.lastname: Han
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qian
authors.forename: Yong
authors.initials: Y
authors.lastname: Liu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D015153:Blotting, Western; D002154:Calpain / Q000502:physiology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D003593:Cytoplasm / Q000378:metabolism; D005260:Female; D007150:Immunohistochemistry; D051379:Mice; D046529:Microscopy, Electron, Transmission; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D018696:Neuroprotective Agents; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D010766:Phosphorylation; D010770:Phosphotransferases / Q000502:physiology*; D011247:Pregnancy; D021381:Protein Transport; D015398:Signal Transduction / Q000187:drug effects; D013778:Tetrazolium Salts; D013844:Thiazoles; D016875:tau Proteins / Q000096:biosynthesis
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; C492236:Cdk5r1 protein, mouse; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D013778:Tetrazolium Salts; D013844:Thiazoles; C074636:amyloid beta-protein (25-35); D016875:tau Proteins; C021751:tanshinone; D010770:Phosphotransferases; D002154:Calpain; C022616:thiazolyl blue