title: Astragaloside IV Attenuates Glutamate-Induced Neurotoxicity in PC12 Cells through Raf-MEK-ERK Pathway.
abstract: Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective, antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In the present study, we employed a high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. Differential proteins were identified, among which 13 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (vimentin and Gap43) were randomly selected, and their expression levels were further confirmed by western blots analysis. The results matched well with those of proteomics. Furthermore, network analysis of protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated proteins were carried out to illustrate its underlying molecular mechanism. Proteins associated with signal transduction, immune system, signaling molecules and interaction, and energy metabolism play important roles in neuroprotective effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This study demonstrates that comparative proteomics based on shotgun approach is a valuable tool for molecular mechanism studies, since it allows the simultaneously evaluate the global proteins alterations.
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Yue
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Bingyang
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Mathematics, Logistical Engineering University, Chongqing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: School of Pharmacy, East China University of Science and Technology, Shanghai, China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: He
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Hu
authors.initials: H
authors.lastname: Yuan
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Yuan
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Guozhen
authors.initials: G
authors.lastname: Wu
authors.affiliation: School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Huizi
authors.initials: H
authors.lastname: Jin
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shan
authors.affiliation: School of Pharmacy, Second Military Medical University, Shanghai, China; School of Pharmacy, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018698:Glutamic Acid / Q000633:toxicity*; D057166:High-Throughput Screening Assays; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000378:metabolism; D058977:Molecular Sequence Annotation; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D016716:PC12 Cells; D025341:Principal Component Analysis; D025941:Protein Interaction Mapping; D051381:Rats; D012503:Saponins / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D014315:Triterpenes / Q000494:pharmacology*; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D018698:Glutamic Acid; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D020930:MAP Kinase Kinase Kinases