title: The protective effects of tanshinone IIA on β-amyloid protein (1-42)-induced cytotoxicity via activation of the Bcl-xL pathway in neuron.
abstract: The deposition of β-amyloid protein(Aβ) and loss of neurons within the brain are the pathologic hallmarks of Alzheimer's disease (AD). Apoptosis is a crucial pathway in neuronal loss in AD. Tanshinone IIA (tanIIA) is one of ingredients of tanshinone which is the major component of the traditional Chinese herb Danshen. The present study explores the effects of tanIIA on Aβ(1-42)-induced cytotoxicity. Cultured cortical neurons that were treated with 4 μM Aβ(1-42) showed shrunken perikaryon with loss of neurite processes; the survival rate of neurons decreased almost to 57% and the apoptotic rate of neurons increased to 47%. In addition, the level of gene bcl-xl mRNA and Bcl-xL protein decreased significantly. These changes, however, were prevented by pretreatment of neurons with tanIIA for 24h before Aβ(1-42), which markedly increased neuron survival rate compared to neurons treated with Aβ(1-42) alone; the apoptotic rate of neurons decreased to 15%, and the decrease in level of gene bcl-xl mRNA and Bcl-xL protein in Aβ-treated neurons, were prevented. Thus, we conclude that tanIIA might serve as an obvious neuroprotection. TanIIA protected neurons against the Aβ-induced cytotoxicity most likely via activation of the Bcl-xL 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, China. qianyh38@mail.xjtu.edu.cn
authors.forename: Yi-Hua
authors.initials: YH
authors.lastname: Qian
authors.forename: Qingli
authors.initials: Q
authors.lastname: Xiao
authors.forename: Jan
authors.initials: J
authors.lastname: Xu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D015153:Blotting, Western; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051020:bcl-X Protein / Q000378:metabolism*
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D051020:bcl-X Protein; C021751:tanshinone