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

10 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

Fingerprint

Cell Hypoxia
PPAR gamma
Endothelial Cells
Apoptosis
Reactive Oxygen Species
Brain
NADP
Oxidoreductases
9-deoxy-delta-9-prostaglandin D2
Brain Injuries
Small Interfering RNA
Blood Vessels
Down-Regulation
Pharmacology
Hypoxia

Keywords

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

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

15-Deoxy-∆12,14-PGJ2, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis. / Wu, Jui Sheng; Tsai, Hsin Da; Huang, Chien Yu; Chen, Jin Jer; Lin, Teng Nan.

In: Molecular Neurobiology, Vol. 50, No. 1, 02.10.2014, p. 221-238.

Research output: Contribution to journalReview article

@article{75e376a49bd74d64b694dfd3b7418691,
title = "15-Deoxy-∆12,14-PGJ2, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis",
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.",
keywords = "Gene regulation, NF-κB, Nox2, Oxygen–glucose deprivation, Superoxide dismutase 1",
author = "Wu, {Jui Sheng} and Tsai, {Hsin Da} and Huang, {Chien Yu} and Chen, {Jin Jer} and Lin, {Teng Nan}",
year = "2014",
month = "10",
day = "2",
doi = "10.1007/s12035-013-8600-x",
language = "English",
volume = "50",
pages = "221--238",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "1",

}

TY - JOUR

T1 - 15-Deoxy-∆12,14-PGJ2, by Activating Peroxisome Proliferator-Activated Receptor-Gamma, Suppresses p22phox Transcription to Protect Brain Endothelial Cells Against Hypoxia-Induced Apoptosis

AU - Wu, Jui Sheng

AU - Tsai, Hsin Da

AU - Huang, Chien Yu

AU - Chen, Jin Jer

AU - Lin, Teng Nan

PY - 2014/10/2

Y1 - 2014/10/2

N2 - 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.

AB - 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.

KW - Gene regulation

KW - NF-κB

KW - Nox2

KW - Oxygen–glucose deprivation

KW - Superoxide dismutase 1

UR - http://www.scopus.com/inward/record.url?scp=84911001504&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911001504&partnerID=8YFLogxK

U2 - 10.1007/s12035-013-8600-x

DO - 10.1007/s12035-013-8600-x

M3 - Review article

VL - 50

SP - 221

EP - 238

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 1

ER -