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- W2076705091 abstract "Cyclooxygenase (COX) catalyzes the formation of prostaglandins from arachidonic acid. 15-Deoxy-delta (12,14)-prostaglandinJ2 (15d-PGJ2), a terminal dehydration product of prostaglandin D2, is an endogenous ligand of peroxisome proliferator-activated receptor- gamma (PPAR-γ). It is reported that, 15d-PGJ2 has neuroprotective effects induction of Nrf-2 activation as well as PPAR-γ expression. NS-398, a COX-2 inhibitor, has also been reported to exert neuroprotection in some contexts. In this study, we sought to determine whether co-administration of COX-2 inhibitor and PPAR-γ ligand will produce higher neuroprotection, and the involved mechanisms in PC12 cells. Using PC12 adrenal pheochromocytoma cells, the levels of NF-κB, Nrf2, ?-glutamylcysteine synthetase (?-GCS), hemeoxygenase (HO-1) and PPAR-γ were determined in the experimental groups using Western blot. Cell viability was determined by the conventional MTT (3-[4,5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) reduction assay. : Pretreatment of PC12 cells with NS-398 (COX-2 inhibitor), followed by exposure to LPS resulted in about 58% higher cell viability relative to the LPS-treated cells. The group that received NS-398, 15d-PGJ2 and LPS, showed higher cell viability (%69), as well as significantly increased expression of PPAR-γ, Nrf-2 and HO-1 and γ-GCS, which are considered as downstream products of activated Nrf-2 pathway. In the group that received NS-398, 15d-PGJ2, GW-9662 (PPAR-γinhibitor) and LPS, both cell viability and the expression of Nrf-2 and PPAR-γ decreased compared to the pervious group. Results indicated that protective effects of co-administration of NS-398 and 15d-PGJ2 in the context of this study are PPAR-γ-dependent. It is suggested that combination therapy with NS-398 and 15d-PGJ2 will result in a stronger neuroprotective outcome, compared to using them alone." @default.
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- W2076705091 date "2011-07-01" @default.
- W2076705091 modified "2023-09-27" @default.
- W2076705091 title "P3-288: Inhibition of PPAR-γ using GW, attenuates transcription factor Nrf-2 expression in PC12 cells" @default.
- W2076705091 doi "https://doi.org/10.1016/j.jalz.2011.05.1730" @default.
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