Volume 3, Issue 2 (Winter 2012 -- 2012)                   BCN 2012, 3(2): 47-55 | Back to browse issues page

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15-Deoxy-Δ12,14-Prostaglandin J2 Protects PC12 cells from LPS-Induced Cell Death Through Nrf2 pathway in PPAR-γ Dependent Manner
Shahnaz Babaei Abraki * , Parnian Eslami , Fariba Khodagholi
Abstract:  

Introduction:

The inflammatory response requires a coordinated integration of various signaling pathway including cyclooxygenase (COX). COX catalyzes the formation of prostaglandins from arachidonic acid. Among prostaglandins, 15-Deoxy-D12, 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 15d-PGJ2 as a PPAR-γ ligand could exert neuroprotective effects in rat pheochromocytoma (PC12) cells in PPAR-γ dependent manner. In our experiment, using PC12 cells, the levels of NF-κB, Nrf2, γ-glutamylcysteine synthetase (γ-GCS), hemeoxygenase (HO-1) and apoptosis factors were determined using Western blot in different groups. Also cell viability was determined by the conventional MTT (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) reduction assay and two staining involved Hoechst staining and Acridine Ordange/Ethidiume Bromide staining respectively.

Results:

Our results show that NS-398, a selective COX-2 inhibitor and 15d-PGJ2, a natural potent ligand of PPAR-γ, were neuroprotective through modulation of at least three different, but related pathways and molecules, including NF-κB and Nrf2 signaling pathway. Our data showed that 15d-PGJ2 and NS-398 induced Nrf2 signaling pathway and its downstream factors such as HO-1 and γ-GCS, while 15d-PGJ2 and NS-398 decreased NF-κB level. Interestingly, the observed protective effects were mediated through PPAR-γ-dependent mechanisms, as they reversed by GW9662, an irreversible antagonist of PPAR-γ receptor.

Discussion:

Thus we conclude that 15d-PGJ2 as well as NS-398 exert anti cell death effect in a PPAR-γ dependent mechanisms.

Methods:

Keywords: Cyclooxygenase, PPAR-γ, PC12, Nrf2, 15d-PGJ2, Neuroprotective.
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Type of Study: Original | Subject: Clinical Neuroscience
Received: 2012/04/19 | Published: 2012/02/15
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