Download Peroxisome proliferator-activated receptor-γ (PPAR

PPAR-γ attenuates oxidative-inflammatory damage in acute ischemic stroke: mechanisms and clinical
perspective
Teng-Nan Lin
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Dr. Teng-Nan Lin
Teng-Nan Lin, PhD, is a Research Fellow and Deputy Director in the Institute of Biomedical Sciences
(IBMS) at Academia Sinica, Taipei, Taiwan. He received his bachelor’s degree from the Tunghai University
in Taiwan and his doctorate in neurochemistry from the University of Missouri-Columbia. He was a
postdoctoral associate at Baylor College of Medicine where he investigated the neurotransmission
mechanisms underlying the ischemic stroke. Since joining IBMS, his research group has unraveled the role
of COX-PGJ2-PPAR-γ axis in cerebral ischemic stroke and identified the anti-neuronal apoptosis
mechanism of PPAR-γ.
Abstract
Peroxisome Proliferator-Activated Receptor-γ (PPAR-γ) protects neurons against ischemic insult by
attenuating reactive oxygen species (ROS) production. However, the detailed molecular mechanism is not
fully understood. Recent studies indicated that nicotinamide adenine dinucleotide phosphate (NADPH)
oxidase is one of the major sources of ROS in ischemic brain. In the present study, we used an in vitro
oxygen-glucose deprivation and reoxygenation paradigm to study whether PPAR-γ interacts with NADPH
oxidase, thereby regulating ROS formation in primary cortical neurons. With pharmacological,
loss-of-function and gain-of-function approaches, we demonstrated that 15d-PGJ2 protected neurons
against ROS-induced apoptosis in a PPAR-γ-dependent manner. Results of reporter and ChIP assays as
well as subcellular localization and confocal analyses further revealed that 15d-PGJ2, by activating
PPAR-γ, blocked hypoxia-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 ischemic-activated p22phox transcription and the subsequent NADPH oxidase
activation, ROS formation, and ischemic brain damage.
Name
Teng-Nan Lin
Institution
Institute of
Biomedical
Sciences,
Academia Sinica
Address
128, Academia
Road, Section 2,
Nankang, Taipei,
Taiwan
Tel
886-2-27899141
E-mail
[email protected]