Pioglitazone protects PC12 cells against oxidative stress injury: An <em>in vitro</em> study of its antiapoptotic effects via the PPARγ pathway

Li,Yali; Long,Jun; Li,Libo; Yu,Ziyao; Liang,Yanjing; Hou,Bin; Xiang,Li; Niu,Xiaolin

doi:10.3892/etm.2023.12221

Pioglitazone protects PC12 cells against oxidative stress injury: An in vitro study of its antiapoptotic effects via the PPARγ pathway

Authors:
- Yali Li
- Jun Long
- Libo Li
- Ziyao Yu
- Yanjing Liang
- Bin Hou
- Li Xiang
- Xiaolin Niu
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Affiliations: Department of Rehabilitation, Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University, Weihai, Shandong 264200, P.R. China, Department of Rehabilitation, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, College of Sports and Health, Shandong Sport University, Jinan, Shandong 250000, P.R. China, Department of Neurology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China, Department of Cardiology, The Second Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
Published online on: September 22, 2023 https://doi.org/10.3892/etm.2023.12221
Article Number: 522
Copyright: © Li et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

To the best of our knowledge, the role of peroxisome proliferator‑activated receptor γ (PPARγ) in oxidative stress‑induced PC12 cell damage is unknown. Using a PC12 cell model with H₂O₂ treatment, the present study investigated the expression levels of apoptosis‑related genes and neuronal apoptosis after oxidative stress injury. The present study further investigated the protective effect and mechanism of pioglitazone, a PPARγ agonist. PC12 cells treated with H₂O₂ were used as a model of oxidative stress injury. An MTT assay and flow cytometry were used to detect the effect of H₂O₂ on PC12 cell viability and the protective effect of pioglitazone. A TUNEL assay was used to detect neuronal apoptosis. The expression levels of PPARγ, Bax, Bcl‑2 and caspase‑3 were examined by reverse transcription‑quantitative PCR and western blotting. H₂O₂ reduced PC12 cell viability in a dose‑ and time‑dependent manner. H₂O₂ significantly upregulated the protein expression levels of Bax and the cleaved caspase‑3/caspase‑3 ratio (P<0.01), decreased the protein expression levels of Bcl‑2 (P<0.01), and increased the apoptosis rate of PC12 cells. Pioglitazone significantly reduced the protein expression levels of Bax and the cleaved caspase‑3/caspase‑3 ratio (P<0.01), increased the expression levels of Bcl‑2 (P<0.01), decreased the Bax/Bcl‑2 expression ratio (P<0.01) and increased the viability of H₂O₂‑damaged PC12 cells in a dose‑dependent manner. Treatment with the PPARγ antagonist GW9662 or PPARγ small interfering RNA counteracted the protective effect of pioglitazone on PC12 cells to different extents (P<0.01). Therefore, the present study reported the role of PPARγ in protecting PC12 cells against oxidative stress injury, which may lead to novel therapeutic approaches for neurodegenerative diseases.

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