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Angiotensin II induces peroxisome proliferator‐activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation
Author(s) -
Zhao Yi,
ForystLudwig Anna,
Bruemmer Dennis,
Culman Juraj,
Bader Michael,
Unger Thomas,
Kintscher Ulrich
Publication year - 2005
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03275.x
Subject(s) - neurite , angiotensin ii , receptor , neuroprotection , peroxisome proliferator activated receptor , microbiology and biotechnology , angiotensin ii receptor type 1 , endocrinology , medicine , biology , chemistry , pharmacology , biochemistry , in vitro
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.