title: Phosphoproteomic profiling of selenate-treated Alzheimer's disease model cells.
abstract: The reversible phosphorylation of proteins regulates most biological processes, while abnormal phosphorylation is a cause or consequence of many diseases including Alzheimer's disease (AD). One of the hallmarks of AD is the formation of neurofibrillary tangles (NFTs), which is composed of hyperphosphorylated tau proteins. Sodium selenate has been recently found to reduce tau hyperphosphorylation and NFTs formation, and to improve spatial learning and motor performance in AD mice. In the current study, the phosphoproteomics of N2aSW cells treated with selenate were investigated. To avoid missing low-abundance phosphoproteins, both the total proteins of cells and the phosphor-enriched proteins were extracted and subjected to the two-dimensional gel electrophoresis with Pro-Q diamond staining and then LC-MS/MS analysis. A total of 65 proteins were altered in phosphorylation level, of which 39 were up-regulated and 26 were down-regulated. All identified phosphoproteins were bioinformatically annotated according to their physiochemical features, subcellular location, and biological function. Most of these significantly changed phosphoproteins are involved in crucial neural processes such as protesome activity, oxidative stress, cysteine and methionine metabolism, and energy metabolism. Furthermore, decreases were found in homocysteine, phosphor-tau and amyloid β upon selenate treatment. Our results suggest that selenate may intervene in the pathological process of AD by altering the phosphorylation of some key proteins involved in oxidative stress, energy metabolism and protein degradation, thus play important roles in maintaining redox homeostasis, generating ATP, and clearing misfolded proteins and aggregates. The present paper provides some new clues to the mechanism of selenate in AD prevention.
authors.affiliation: College of Life Sciences, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, China; Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Chen
authors.affiliation: Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Lixiang
authors.initials: L
authors.lastname: Wang
authors.affiliation: College of Life Sciences, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Shuiming
authors.initials: S
authors.lastname: Li
authors.affiliation: College of Life Sciences, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Liming
authors.initials: L
authors.lastname: Shen
authors.affiliation: Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Liu
authors.affiliation: College of Life Sciences, Shenzhen Key Laboratory of Microbial Genetic Engineering, Shenzhen University, Shenzhen, 518060, China; Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen, 518060, China.
authors.forename: Jiazuan
authors.initials: J
authors.lastname: Ni
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019295:Computational Biology / Q000379:methods; D006801:Humans; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D058977:Molecular Sequence Annotation; D010750:Phosphoproteins / Q000378:metabolism*; D020543:Proteome; D040901:Proteomics / Q000379:methods; D064586:Selenic Acid / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D000975:Antioxidants; D010750:Phosphoproteins; D020543:Proteome; D064586:Selenic Acid