Protein profile in neuroblastoma cells incubated with S- and R-enantiomers of ibuprofen by iTRAQ-coupled 2-D LC-MS/MS analysis: possible action of induced proteins on Alzheimer's disease.
Ibuprofen is a member of the proprionic acid group of nonsteroidal anti-inflammatory drugs (NSAID), with the S-enantiomer being more active than the R-enantiomer. It has been shown to display protective effects against neuroinflammation, which is linked to the pathogenesis of several neurodegenerative disorders, including Alzheimer's disease (AD). While its prophylactic effect on AD has been suggested, a comprehensive understanding of its mechanism of action remains unclear. Using iTRAQ-coupled 2-D LC-MS/MS analysis, we report here the first study of protein profiles of neuroblastoma cells incubated separately with the two enantiomers of ibuprofen. Three types of cellular proteins, including metabolic enzymes, signaling molecules and cytoskeletal proteins, displayed changes. The changes in the level of a number of enzymes involved in fatty acid synthesis and antioxidant activity in cells incubated with the S-enantiomer were further supported by the real-time PCR analysis as well as the reduced level of reactive oxygen species in cells incubated with the S-enantiomer of ibuprofen. Our findings, therefore, provide the possible mechanism of ibuprofen-induced proteins on AD, and the beneficial effects of ibuprofen in reducing the development of AD.
Zhang
Jianhua
J
School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore.
Sui
Jianjun
J
Ching
Chi Bun
CB
Chen
Wei Ning
WN
D000544:Alzheimer Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002853:Chromatography, Liquid; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D009447:Neuroblastoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000032:analysis; D020543:Proteome / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015415:Biomarkers; D007202:Indicators and Reagents; D010446:Peptide Fragments; D020543:Proteome; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007052:Ibuprofen