RhFGF21 protected PC12 cells against mitochondrial apoptosis triggered by HO via the AKT-mediated ROS signaling pathway.

One of the pathological mechanisms of neurodegenerative diseases is that oxidative stress damages neurons. Therefore, reducing reactive oxygen species (ROS) overload may be a promising approach for preventing and treating neurological diseases. Fibroblast growth factor 21 (FGF21) is crucial for protecting and restoring various forms of pathological injury. Consequently, the operating mechanism of FGF21 was investigated. Our research revealed that rhFGF21 could enhance the cell viability by alleviating the damage to PC12 cells after HO action of via mechanisms decreasing mitochondrial apoptosis, reducing ROS production, increasing antioxidant enzyme levels, adenosine triphosphate (ATP) synthesis and mitochondrial membrane potential (MMP). Excessive ROS trigger cell apoptosis. Our findings revealed that tBHP counteracted the cell viability-boosting effect of rhFGF21 in HO-stimulated PC12 cells, whereas N-acetyl-L-cysteine (NAC) enhanced the viability-promoting effect of rhFGF21 in these cells. AKT is crucial in mediating ROS-induced cell apoptosis. The treatment of PC12 cells exposed to HO with rhFGF21 resulted in upregulation of p-AKT expression. Moreover, rhFGF21 inhibited ROS levels and increased the cell viability, which were both reversed by administration of an AKT inhibitor (wortmannin). The research discovered that rhFGF21 mitigated mitochondrial apoptosis in PC12 cells exposed to HO through the functioning of the AKT and ROS signaling axis.