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
著者
田崎, 嘉一
(Tasaki, Yoshikazu)
Omura, Tomohiro
Yamada, Takehiro
Ohkubo, Tomoko
Suno, Manabu
Iida, Shinya
Sakaguchi, Tomoki
Asari, Masaru
Shimizu, Keiko
Matsubara, Kazuo
上位タイトル
Brain Research
Vol.1344,
(2010.
7)
,p.25-
33
識別番号
ISSN
0006-8993
DOI
10.1016/j.brainres.2010.04.085
抄録
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.
