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Medical Science Monitor Basic Research


eISSN: 1643-3750

Aggravation of Cerebral Ischemia/Reperfusion Injury by Peroxisome Proliferator-Activated Receptor-Gamma Deficiency via Endoplasmic Reticulum Stress

Yueping Chen, Shihui Liu, Guangyong Chen

Clinical Laboratory, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, Zhejiang, China (mainland)

Med Sci Monit 2019; 25:7518-7526

DOI: 10.12659/MSM.915914

Available online:

Published: 2019-10-07


BACKGROUND: Ischemic stroke is a dominant contributor to disability and mortality worldwide and is recognized as an important health concern. As a transcription factor triggered via stress, peroxisome proliferator-activated receptor-gamma (PPAR-γ) has a crucial impact on differentiation, cell death, and cell growth. However, the role of PPAR-γ and its precise mechanism in cerebral ischemia injury (CII) remain unclear.
MATERIAL AND METHODS: The male C57Bl/6 mice (12 weeks old, n=52) were subjected to middle cerebral artery occlusion (MCAO). Infarct volume was evaluated by 2, 3, 5-Triphenyltetrazolium chloride staining. Cell apoptosis was measured by terminal dUTP nick-end labeling (TUNEL) staining. The expression of apoptotic-related protein was examined by Western blotting. Neuron2A cells were transfected with PPAR-γ-specific siRNA and then were subjected to oxygen-glucose exhaustion and reoxygenation.
RESULTS: It was observed that PPAR-γ-deficient mice displayed extended infarct trigon in the MCAO stroke model. Neuronal deficiency was more severe in PPAR-γ-deficient models. Additionally, expression of cell death-promoting Bcl-2 associated X and active caspase-3 was reinforced, while that of cell death-counteracting Bcl-2 was repressed in PPAR-γ-deficient mice. This was characterized by reinforced endoplasmic reticulum (ER) stress reactions in in vivo brain specimens as well as in vitro neurons in ischemia/reperfusion (I/R) injury.
CONCLUSIONS: This research proved that PPAR-γ protected the brain from cerebral I/R injury by repressing ER stress and indicated that PPAR-γ is a potential target in the treatment of ischemia.

Keywords: Apoptosis Regulatory Proteins, MAP Kinase Kinase Kinase 5