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Oxidant stress modulates PPARγ expression and activity in vascular endothelial cells
Author(s) -
Blanquicett Carmelo,
Ritzenthaler Jeff,
Kleinhenz Dean,
Hart C. Michael
Publication year - 2008
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.22.1_supplement.758.20
Subject(s) - umbilical vein , peroxisome proliferator activated receptor , catalase , chemistry , oxidative stress , messenger rna , receptor , medicine , endocrinology , microbiology and biotechnology , biology , biochemistry , in vitro , gene
The ligand‐activated nuclear transcription factor, peroxisome proliferator‐activated receptor γ (PPARγ), exerts pleiotropic effects on metabolism and inflammation and modulates vascular endothelial nitroso‐redox balance. We hypothesized that oxidant stress alters PPARγ expression and activity, an effect that could be prevented by the antioxidant, catalase. Human umbilical vein endothelial cells (HUVEC) were exposed to 100 μM H 2 O 2 for 0.5–4 h. PPARγ activity and mRNA levels were determined ± catalase addition using a PPARγ activity assay and real‐time PCR, respectively. H 2 O 2 ‐mediated alterations in PPARγ mRNA were examined using Actinomycin‐D and luciferase reporter assays. PPARγ activity in bovine aortic endothelial cells (BAEC) was also examined by altering the extracellular redox potential (E h ), using the cysteine (Cys)/cystine (CySS) couple. Thirty min. following exposure to H 2 O 2 , HUVEC PPARγ activity and mRNA levels were significantly reduced. Catalase prevented H 2 O 2 ‐induced reductions in PPARγ activity and mRNA. Compared with normal (−80 mV) and reduced (−150 mV) E h , treatment with oxidized (0 mV) E h significantly decreased PPARγ activity. Neither H 2 O 2 nor catalase significantly affected PPARγ mRNA half‐life. These findings demonstrate that oxidant stress modulates both PPARγ mRNA and activity in vascular endothelial cells. Supported by grants from the NIH and VA Research Service.