Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway

• Published in: Nutrients 2023-06, Vol.15 (13), p.2973
• Main Authors: Liu, Jie, Mai, Peishi, Yang, Zihui, Wang, Zongwei, Yang, Wei, Wang, Ziyuan
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms - metabolism; Alzheimer's disease; Antibodies; Apoptosis; Autophagy; Cell death; Cells; Flow cytometry; Homeostasis; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Membrane potential; Microcomputers; Mitochondria; Mitochondria - metabolism; mitochondrial function; Neurophysiology; Oxidation; oxidative damage; Oxidative Stress; Penicillin; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - genetics; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Pheochromocytoma; Pheochromocytoma - metabolism; Physiology; Piceatannol; Proteins; Rapamycin; Reactive oxygen species; SIRT3; Sirtuin 3 - genetics; Sirtuin 3 - metabolism
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15132973

Oxidative stress has been identified as a major cause of cellular injury in a variety of neurodegenerative disorders. This study aimed to investigate the cytoprotective effects of piceatannol on hydrogen peroxide (H O )-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H O -induced PC-12 cell death. Furthermore, piceatannol effectively improved mitochondrial content and mitochondrial function, including enhancing mitochondrial reactive oxygen species (ROS) elimination capacity and increasing mitochondrial transcription factor (TFAM), peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria Complex IV expression. Meanwhile, piceatannol treatment inhibited mitochondria-mediated autophagy as demonstrated by restoring mitochondrial membrane potential, reducing autophagosome formation and light chain 3B II/I (LC3B II/I) and autophagy-related protein 5 (ATG5) expression level. The protein expression level of SIRT3 was significantly increased by piceatannol in a concentration-dependent manner. However, the cytoprotective effect of piceatannol was dramatically abolished by sirtuin 3 (SIRT3) inhibitor, 3-(1H-1,2,3-Triazol-4-yl) pyridine (3-TYP), which led to an exacerbated mitochondrial dysfunction and autophagy in PC-12 cells under oxidative stress. In addition, the autophagy activator (rapamycin) abrogated the protective effects of piceatannol on PC-12 cell death. These findings demonstrated that piceatannol could alleviate PC-12 cell oxidative damage and mitochondrial dysfunction by inhibiting autophagy via the SIRT3 pathway.