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
- PMID: 20452332
- DOI: 10.1016/j.brainres.2010.04.085
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
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 4h 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.
Copyright (c) 2010 Elsevier B.V. All rights reserved.
Similar articles
-
Meloxicam ameliorates motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling in a mouse Parkinson's disease model.Neurosci Lett. 2012 Jul 11;521(1):15-9. doi: 10.1016/j.neulet.2012.05.045. Epub 2012 May 19. Neurosci Lett. 2012. PMID: 22617635
-
Oxicam structure in non-steroidal anti-inflammatory drugs is essential to exhibit Akt-mediated neuroprotection against 1-methyl-4-phenyl pyridinium-induced cytotoxicity.Eur J Pharmacol. 2012 Feb 15;676(1-3):57-63. doi: 10.1016/j.ejphar.2011.11.046. Epub 2011 Dec 7. Eur J Pharmacol. 2012. PMID: 22182582
-
Oxicam-derived non-steroidal anti-inflammatory drugs suppress 1-methyl-4-phenyl pyridinium-induced cell death via repression of endoplasmic reticulum stress response and mitochondrial dysfunction in SH-SY5Y cells.Biochem Biophys Res Commun. 2018 Sep 18;503(4):2963-2969. doi: 10.1016/j.bbrc.2018.08.078. Epub 2018 Aug 11. Biochem Biophys Res Commun. 2018. PMID: 30107908
-
SH-SY5Y human neuroblastoma cell line: in vitro cell model of dopaminergic neurons in Parkinson's disease.Chin Med J (Engl). 2010 Apr 20;123(8):1086-92. Chin Med J (Engl). 2010. PMID: 20497720 Review.
-
COX-2 and neurodegeneration in Parkinson's disease.Ann N Y Acad Sci. 2003 Jun;991:272-7. doi: 10.1111/j.1749-6632.2003.tb07482.x. Ann N Y Acad Sci. 2003. PMID: 12846993 Review.
Cited by
-
Neuroprotective effects of low-dose G-CSF plus meloxicam in a rat model of anterior ischemic optic neuropathy.Sci Rep. 2020 Jun 25;10(1):10351. doi: 10.1038/s41598-020-66977-9. Sci Rep. 2020. PMID: 32587280 Free PMC article.
-
Design, synthesis and evaluation of indole derivatives as multifunctional agents against Alzheimer's disease.Medchemcomm. 2018 Jan 16;9(2):357-370. doi: 10.1039/c7md00569e. eCollection 2018 Feb 1. Medchemcomm. 2018. PMID: 30108930 Free PMC article.
-
RESP18 is involved in the cytotoxicity of dopaminergic neurotoxins in MN9D cells.Neurotox Res. 2013 Aug;24(2):164-75. doi: 10.1007/s12640-013-9375-6. Epub 2013 Jan 15. Neurotox Res. 2013. PMID: 23319378
-
Versatility of 7-Substituted Coumarin Molecules as Antimycobacterial Agents, Neuronal Enzyme Inhibitors and Neuroprotective Agents.Molecules. 2017 Sep 30;22(10):1644. doi: 10.3390/molecules22101644. Molecules. 2017. PMID: 28973990 Free PMC article.
-
Akt as a victim, villain and potential hero in Parkinson's disease pathophysiology and treatment.Cell Mol Neurobiol. 2011 Oct;31(7):969-78. doi: 10.1007/s10571-011-9671-8. Epub 2011 Mar 10. Cell Mol Neurobiol. 2011. PMID: 21547489 Free PMC article.
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Research Materials
Miscellaneous