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The PPAR‐γ agonist Rosiglitazone increases angiotensin‐converting enzyme 2 (ACE2) promoter activity in neurons
Author(s) -
Scroggin Melissa,
Pedersen Kim B.,
Lazartigues Eric
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.875.13
Subject(s) - rosiglitazone , agonist , endocrinology , medicine , angiotensin ii , receptor , peroxisome proliferator activated receptor , angiotensin converting enzyme 2 , chemistry , activator (genetics) , renin–angiotensin system , reporter gene , homeostasis , gene expression , biology , gene , blood pressure , biochemistry , disease , covid-19 , infectious disease (medical specialty)
Angiotensin converting enzyme 2 (ACE2) converts angiotensin‐(Ang)‐II to the vasodilator peptide Ang‐(1–7). Our laboratory has previously observed that ACE2 expression and activity in brain regions involved in the central regulation of blood pressure (BP) and volume homeostasis (e.g. SFO, PVN, and RVLM) are reduced in mice with elevated brain Ang‐II levels. Other investigators have shown that Rosiglitazone, a peroxisome proliferator‐activator receptor gamma (PPAR‐γ) agonist, increases ACE2 mRNA in adipocytes. Here we assessed the potential of PPAR‐γ to activate the ACE2 gene promoter. A reporter plasmid containing the human ACE2 proximal promoter sequence was constructed, and luciferase activity was measured after transfection of mouse Neuro‐2a cells in the presence or absence of Rosiglitazone (1 μM) and Ang‐II (100 nM) for 24 hours. Human ACE2 promoter activity increased by 2‐fold ( P <0.05) with Rosiglitazone treatment independently of Ang‐II treatment, suggesting that PPAR‐γ may bind the proximal promoter and induce expression of hACE2. On the other hand, our data suggest that Ang‐II regulation of the hACE2 gene expression is not dependent on its proximal promoter. Altogether, we show that PPAR‐γ positively regulates the hACE2 promoter activity, supporting a beneficial role in modulating Ang‐II levels in neurogenic hypertension and in the regulation of volume homeostasis. (Funding: HL093178 )