title: The influence of chronic ibuprofen treatment on proteins expressed in the mouse hippocampus.
abstract: Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID), treatment with which has been shown to delay the onset, slows the cognitive decline, and decreases the incidence of Alzheimer׳s disease (AD) in epidemiological and clinical studies. However, a comprehensive understanding of its mechanism of action remains unclear. To elucidate the prophylactic effect of ibuprofen on the onset of the learning and memory disturbances of AD, we performed proteomic analysis of the hippocampus of chronic ibuprofen-treated mice using two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry. Twenty-eight proteins and seven phosphoproteins were identified to be significantly changed in the hippocampus of chronic ibuprofen-treated mice: translationally controlled tumor protein, thioredoxin-dependent peroxide reductase, and peroxiredoxin 6 were increased, and glial fibrillary acidic protein, dihydropyrimidinase-related protein 2, EF-hand domain-containing protein D2, and 14-3-3ζ were decreased. These identified proteins and phosphoproteins could be classified as cytoskeletal, neuronal development, chaperone, metabolic, apoptosis, neurotransmitter release, ATP synthase, deubiquitination, proteasome, NOS inhibitor, adapter, vesicle transport, signal transduction, antioxidant enzyme, proton transport, synaptogenesis, and serine/threonine phosphatase types. Western blot analysis showed the changes in dihydropyrimidinase-related protein 2, heat shock protein 8, ubiquitin carboxyl-terminal hydrolase PGP9.5, and γ-enolase levels in the hippocampus of chronic ibuprofen-treated mice. These findings showed that the chronic treatment with ibuprofen changed the levels of some proteins and phosphoproteins in the hippocampus. We propose that these identified proteins and phosphoproteins play an important role in decreasing the incidence of AD, especially impaired learning and memory functions.
authors: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan.
authors: Kenji
authors: K
authors: Matsuura
authors: Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan.
authors: Mieko
authors: M
authors: Otani
authors: Department of Life Sciences Pharmacy, School of Pharmaceutical Sciences, Kobe Gakuin University, Kobe 650-8586, Japan.
authors: Masaoki
authors: M
authors: Takano
authors: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan.
authors: Keiichi
authors: K
authors: Kadoyama
authors: Department of Pharmaceutical Health Care, Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, Himeji 670-8524, Japan. Electronic address: shogo@himeji-du.ac.jp.
authors: Shogo
authors: S
authors: Matsuyama
mesh_terms: D000544:Alzheimer Disease / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D007052:Ibuprofen / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010750:Phosphoproteins / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D010750:Phosphoproteins; D011506:Proteins; D007052:Ibuprofen
keywords: Alzheimer׳s disease; Hippocampus; Ibuprofen; Ibuprofen (PubChem CID: 3672).; NSAIDs; Proteomics