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

To the best of our knowledge, the role of peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 PPAR gamma 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 PPAR gamma, 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 PPAR gamma antagonist GW9662 or PPAR gamma 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 PPAR gamma in protecting PC12 cells against oxidative stress injury, which may lead to novel therapeutic approaches for neurodegenerative diseases.