PMID- 37447299 OWN - NLM STAT- MEDLINE DCOM- 20230717 LR - 20230718 IS - 2072-6643 (Electronic) IS - 2072-6643 (Linking) VI - 15 IP - 13 DP - 2023 Jun 30 TI - Piceatannol Protects PC-12 Cells against Oxidative Damage and Mitochondrial Dysfunction by Inhibiting Autophagy via SIRT3 Pathway. LID - 10.3390/nu15132973 [doi] LID - 2973 AB - 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(2)O(2))-induced pheochromocytoma-12 (PC-12) cell damage and explore the underlying mechanisms. Our findings indicated that piceatannol pre-treatment significantly attenuated H(2)O(2)-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-gamma coactivator-1alpha (PGC-1alpha) 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. FAU - Liu, Jie AU - Liu J AUID- ORCID: 0000-0003-0843-0358 AD - Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University (BTBU), Beijing 100048, China. AD - China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology and Business University (BTBU), Beijing 100048, China. FAU - Mai, Peishi AU - Mai P AD - Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University (BTBU), Beijing 100048, China. FAU - Yang, Zihui AU - Yang Z AD - Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University (BTBU), Beijing 100048, China. FAU - Wang, Zongwei AU - Wang Z AD - Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University (BTBU), Beijing 100048, China. FAU - Yang, Wei AU - Yang W AD - College of Basic Science, Tianjin Agricultural University, Tianjin 300392, China. FAU - Wang, Ziyuan AU - Wang Z AUID- ORCID: 0000-0002-7095-8527 AD - Key Laboratory of Geriatric Nutrition and Health, Ministry of Education, Beijing Technology and Business University (BTBU), Beijing 100048, China. AD - China-Canada Joint Lab of Food Nutrition and Health (Beijing), Beijing Technology and Business University (BTBU), Beijing 100048, China. LA - eng GR - BPHR202203044/Project of Cultivation for young top-notch Talents of Beijing Municipal Institutions/ GR - KM202110011004/General Project of Beijing Municipal Commission of Education/ GR - 2021CXGC010807-03/Key R&D Program of Shandong Province/ PT - Journal Article DEP - 20230630 PL - Switzerland TA - Nutrients JT - Nutrients JID - 101521595 RN - EC 3.5.1.- (Sirtuin 3) RN - 6KS3LS0D4F (3,3',4,5'-tetrahydroxystilbene) RN - BBX060AN9V (Hydrogen Peroxide) RN - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha) RN - EC 3.5.1.- (SIRT3 protein, human) SB - IM MH - Humans MH - *Sirtuin 3/genetics/metabolism MH - Hydrogen Peroxide/metabolism MH - *Pheochromocytoma/metabolism MH - Oxidative Stress MH - Mitochondria/metabolism MH - Autophagy MH - *Adrenal Gland Neoplasms/metabolism MH - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/genetics/metabolism PMC - PMC10346636 OTO - NOTNLM OT - SIRT3 OT - autophagy OT - mitochondrial function OT - oxidative damage OT - piceatannol COIS- The authors declare that there are no conflict of interest. EDAT- 2023/07/14 13:06 MHDA- 2023/07/17 06:42 PMCR- 2023/06/30 CRDT- 2023/07/14 01:22 PHST- 2023/05/19 00:00 [received] PHST- 2023/06/22 00:00 [revised] PHST- 2023/06/25 00:00 [accepted] PHST- 2023/07/17 06:42 [medline] PHST- 2023/07/14 13:06 [pubmed] PHST- 2023/07/14 01:22 [entrez] PHST- 2023/06/30 00:00 [pmc-release] AID - nu15132973 [pii] AID - nutrients-15-02973 [pii] AID - 10.3390/nu15132973 [doi] PST - epublish SO - Nutrients. 2023 Jun 30;15(13):2973. doi: 10.3390/nu15132973.