15-Deoxy-∆12,14-PGJ2, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis

Jui Sheng Wu, Hsin Da Tsai, Chien Yu Huang, Jin Jer Chen, Teng Nan Lin

Research output: Contribution to journalReview article

12 Citations (Scopus)

Abstract

15-Deoxy-∆12,14-PGJ2(15d-PGJ2) and thiazolidinedione attenuate reactive oxygen species (ROS) production via a peroxisome proliferator-activated receptor-gamma (PPAR-γ)-dependent pathway. Nonetheless, how PPAR-γ mediates ROS production to ameliorate ischemic brain injury is not clear. Recent studies indicated that nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is the major source of ROS in the vascular system. In the present study, we used an in vitro oxygen–glucose deprivation and reoxygenation (hypoxia reoxygenation [HR]) paradigm to study whether PPAR-γ interacts with NADPH oxidase, thereby regulating ROS formation in cerebral endothelial cells (CECs). With pharmacological (PPAR-γ antagonist GW9662), loss-of-function (PPAR-γ siRNA), and gain-of-function (Ad-PPAR-γ) approaches, we first demonstrated that 15d-PGJ2protected HR-treated CECs against ROS-induced apoptosis in a PPAR-γ-dependent manner. Results of promoter and subcellular localization analyses further revealed that 15d-PGJ2, by activating PPAR-γ, blocked HR-induced NF-κB nuclear translocation, which led to inhibited transcription of the NADPH oxidase subunit p22phox. In summary, we report a novel transrepression mechanism whereby PPAR-γ downregulates hypoxia-activated p22phox transcription and the subsequent NADPH oxidase activation, ROS formation, and CEC apoptosis.

Original languageEnglish
Pages (from-to)221-238
Number of pages18
JournalMolecular Neurobiology
Volume50
Issue number1
DOIs
Publication statusPublished - Oct 2 2014
Externally publishedYes

Keywords

  • Gene regulation
  • NF-κB
  • Nox2
  • Oxygen–glucose deprivation
  • Superoxide dismutase 1

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of '15-Deoxy-∆<sup>12,14</sup>-PGJ<sub>2</sub>, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis'. Together they form a unique fingerprint.

  • Cite this