Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation
Article first published online: 30 JUN 2005
Journal of Neurochemistry
Volume 94, Issue 5, pages 1395–1401, September 2005
How to Cite
Zhao, Y., Foryst-Ludwig, A., Bruemmer, D., Culman, J., Bader, M., Unger, T. and Kintscher, U. (2005), Angiotensin II induces peroxisome proliferator-activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation. Journal of Neurochemistry, 94: 1395–1401. doi: 10.1111/j.1471-4159.2005.03275.x
- Issue published online: 30 JUN 2005
- Article first published online: 30 JUN 2005
- Received January 27, 2005; revised manuscript received May 3, 2005; accepted May 5, 2005.
- angiotensin II;
- angiotensin receptors;
- cell differentiation;
- peroxisome proliferator-activated receptor gamma
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.