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Published on: November 18, 2022
Piceatannol alleviate ROS-mediated PC-12 cells damage and mitochondrial dysfunction through SIRT3/FOXO3a signaling
Wei Yang1,2, Yu Wang1, Yiming Hao1
1China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology and Business University (BTBU), Beijing, China.
Abstract:
Oxidative stress-associated mitochondrial dysfunction has been identified as a major mechanism in multiple neurodegenerative diseases. This study aims to investigate the cytoprotective effects of piceatannol on ROS-mediated PC-12 cells damage and related mitochondrial dysfunction. Piceatannol treatment could significantly attenuate PC-12 cells oxidative damage and ROS-mediated cells apoptosis. Moreover, pretreatment with piceatannol effectively decreased mitochondrial membrane depolarization, cleaved-caspase 3, and increased Bcl-2 and Bcl-2/Bax compared with control H2 O2 group. Meanwhile, piceatannol treatment improved mitochondrial respiration function which led to an enhancement in the maximal respiration and spare respiratory capacity. Further mechanisms analysis showed that the protein expression of SIRT3 and its downstream protein FOXO3a were significantly increased after piceatannol addition in a dose-dependent manner. Whereas the cytoprotective role of piceatannol was markedly abolished by the SIRT3 inhibitor 3-TYP, suggesting that SIRT3/FOXO3a signaling pathway played a vital role in mediating the neuronal cytoprotective effects of piceatannol. PRACTICAL APPLICATIONS: The results of our study provide a novel insight that piceatannol could be potentially used as a promising bioactive component against oxidative damage and neurocyte apoptosis. The findings may provide theoretical basis for brain health of piceatannol consumption in some extent.
Insights
Piceatannol protects against oxidative stress and neuronal apoptosis by improving mitochondrial function. This compound activates the SIRT3/FOXO3a pathway, offering potential benefits for brain health.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Oxidative stress and mitochondrial dysfunction are key factors in neurodegenerative diseases.
- PC-12 cells are a common model for studying neuronal damage.
Purpose of the Study:
- To investigate the protective effects of piceatannol against reactive oxygen species (ROS)-induced damage in PC-12 cells.
- To elucidate the role of mitochondrial function and the SIRT3/FOXO3a pathway in piceatannol's cytoprotective mechanism.
Main Methods:
- PC-12 cells were exposed to hydrogen peroxide (H2O2) to induce oxidative stress.
- Piceatannol treatment was administered, followed by assessments of cell viability, apoptosis markers (cleaved-caspase 3, Bcl-2/Bax ratio), mitochondrial membrane potential, and mitochondrial respiration.
- Western blotting was used to analyze the expression of SIRT3 and FOXO3a proteins.
- The SIRT3 inhibitor 3-TYP was employed to confirm pathway involvement.
Main Results:
- Piceatannol significantly reduced H2O2-induced oxidative damage and apoptosis in PC-12 cells.
- It preserved mitochondrial membrane potential, decreased cleaved-caspase 3, and modulated Bcl-2 family proteins.
- Piceatannol enhanced mitochondrial respiration, increasing maximal respiration and spare respiratory capacity.
- Dose-dependent increases in SIRT3 and FOXO3a protein expression were observed.
- Inhibition of SIRT3 abolished the protective effects of piceatannol.
Conclusions:
- Piceatannol exhibits significant cytoprotective effects against oxidative stress and apoptosis in neuronal cells.
- These effects are mediated through the enhancement of mitochondrial function and the activation of the SIRT3/FOXO3a signaling pathway.
- Piceatannol shows promise as a therapeutic agent for neurodegenerative conditions linked to oxidative damage.
