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Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation

Item Type:Article
Title:Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation
Creators Name:Zhao, Y. and Foryst-Ludwig, A. and Bruemmer, D. and Culman, J. and Bader, M. and Unger, T. and Kintscher, U.
Abstract:The angiotensin type 2 (AT2) receptor has been previously demonstrated to exert neuroprotective actions possibly by inducing neuronal cell differentiation involving neurite outgrowth. The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARγ) is an important transcriptional regulator of cell differentiation. The aim of the present study was to clarify whether PPARγ is involved in AT2-receptor-mediated morphological neuronal cell differentiation. To investigate AT2-receptor- mediated morphological neuronal cell differentiation, rat pheochromocytoma cells (PC12W cells) expressing AT2 but not AT1 receptors, were stimulated with angiotensin II (Ang II, 100 nmol/L) ± the PPARγ antagonists GW9662 (3 μmol/L) and bisphenol A diglycidyl ether (BADGE, 1 μmol/L), and neurite outgrowth of these cells was assessed. Ang II induced neurite outgrowth by 19 ± 1.6-fold (p<0.01). Antagonizing PPARγ activity by GW9662 or BADGE potently blocked Ang II-induced neurite outgrowth (Ang II + GW9662: 6.6 ± 1.5-fold, p < 0.05; Ang II + BADGE: 1.3 ± 0.7-fold, p < 0.01). AT2 receptor activation by Ang II markedly induced mRNA and protein expression of the PPARγ2 isoform and enhanced ligand-induced PPARγ activity in transactivation assays. In conclusion, the present study demonstrates that Ang II induces PPARγ expression and ligand-mediated PPARγ activity via AT2 receptor activation, which appears to be a crucial process in AT2 receptor mediated neurite outgrowth. AT2 receptor/PPARγ- dependent neurite outgrowth may play an important role during neuroprotective processes.
Keywords:Angiotensin II, Angiotensin Receptors, Cell Differentiation, Neuroprotection, Peroxisome Proliferator-Activated Receptor Gamma, Animals, Rats
Source:Journal of Neurochemistry
ISSN:0022-3042
Publisher:Blackwell Publishing (U.K.)
Volume:94
Number:5
Page Range:1395-1401
Date:30 June 2005
Official Publication:https://doi.org/10.1111/j.1471-4159.2005.03275.x
PubMed:View item in PubMed

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