Meloxicam protects cell damage from 1-methyl-4-phenyl pyridinium toxicity via the phosphatidylinositol 3-kinase/Akt pathway in human dopaminergic neuroblastoma SH-SY5Y cells

Yoshikazu Tasaki, Tomohiro Omura, Takehiro Yamada, Tomoko Ohkubo, Manabu Suno, Shinya Iida, Tomoki Sakaguchi, Masaru Asari, Keiko Shimizu, Kazuo Matsubara

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal death in the substantia nigra pars compacta. There is growing interest in the effects of nonsteroidal antiinflammatory drugs (NSAIDs) against PD progression. In this study, we investigated the neuroprotective effect of NSAIDs on neuronal damage induced by 1-methyl-4-phenyl pyridinium (MPP+) in human dopaminergic SH-SY5Y neuroblastoma cells. Of the NSAIDs tested, only meloxicam indicated protective effect on MPP+-induced neurotoxicity in SH-SY5Y cells, although such an effect was not established with indomethacin, ibuprofen and cyclooxygenase (COX)-2 selective inhibitors (NS-398 and CAY-10404). The neuroprotective effect of meloxicam against MPP+ toxicity was specific, as toxicities induced by other cytotoxic agents (such as rotenone, MG-132, tunicamycin and ethacrynic acid) were not attenuated by meloxicam. The neuroprotective effect of meloxicam on MPP+-induced apoptosis was abolished by a phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002, but not by a MEK inhibitor, PD98059. The Akt phosphorylation levels were predominantly suppressed 4 h after MPP+ incubation (i.e. when the cell toxicity was not apparently observed yet). Meloxicam completely prevented the Akt phosphorylation suppression caused by MPP+ exposure, while meloxicam per se did not promote the Akt phosphorylation. These results strongly suggest that the neuroprotective effect of meloxicam is mediated by the maintenance of cell survival signaling in the PI3K/Akt pathway, but not by COX-2 inhibition. Therefore, meloxicam may have therapeutic potential in preventing development or delaying progress of PD.

Original languageEnglish
Pages (from-to)25-33
Number of pages9
JournalBrain Research
Volume1344
DOIs
Publication statusPublished - Jul 16 2010

Keywords

  • Akt
  • MPP
  • Meloxicam
  • NSAID
  • Neuroprotection
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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