Simultaneous inhibition of COX-2 and activation of PPAR-γ resulted in the same level and pattern of neuroprotection as they were targeted separately

(2013) Simultaneous inhibition of COX-2 and activation of PPAR-γ resulted in the same level and pattern of neuroprotection as they were targeted separately. Journal of Molecular Neuroscience.

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Abstract

The inflammatory response is an immune response of the body when exposed to internal and external stimuli. Cyclooxygenases (COX) are major inflammatory mediators implicated in inflammation. COX-2 is reported to be involved in neuroinflammation. Moreover, 15-Deoxy-d 12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPAR-γ), has been demonstrated to have anti-inflammatory actions. In this study, we investigated whether co-therapy of a selective COX-2 inhibitor NS-398 and 15d-PGJ2 as a PPAR-γ ligand could exert additional neuroprotective effects in rat pheochromocytoma (PC12) cells. Our findings showed that 15d-PGJ2 and NS-398 suppress the apoptotic pathway in PC12 cells exposed to H2O2 by attenuation of the Bax/Bcl-2 ratio. This effect was mediated through PPAR-γ, as it was reversed by GW9662 (a PPAR-γ inhibitor). Also, 15d-PGJ2 and NS-398 induced the Nrf2 signaling pathway and decreased NF-κB level in a PPAR-γ-dependent manner. We found that coadministration of a selective COX-2 inhibitor and a PPAR-γ ligand in PC12 cells has equal neuroprotective effect compared to their effects when used separately. Considering the higher affinity of 15d-PGJ2 for PPAR-γ than NS-398, it seems that the observed neuroprotection of this combination therapy was from 15d-PGJ2. © 2012 Springer Science+Business Media New York.

Item Type: Article
Additional Information: cited By
Keywords: 15d-PGJ2; Cyclooxygenase-2; Neuroprotection; NF-κB; Nrf2; PPAR-γ
Subjects: pharmacology
Divisions: Education Vice-Chancellor Department > Faculty of Medicine > Department of Basic Science > Department of Physiology Pharmacology Medical
Depositing User: دکتر مهری غلامی
URI: http://eprints.abzums.ac.ir/id/eprint/1929

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