Resveratrol Improves Mitochondrial Biogenesis Function and Activates PGC-1α Pathway in a Preclinical Model of Early Brain Injury Following Subarachnoid Hemorrhage

Frontiers in Molecular Biosciences

Huiduan Zheng¹  Zhenggang Chen²  Jian Zhou²  Wangwang Zhong²  Jianjian Tang²  Ruiming Shen³  Juan Zhu⁴  Zaijia Yang⁵ 

[1] Department of Neurology, Hainan Provincial People’s Hospital, Haikou, China;Department of Neurosurgery, The First Affiliated Hospital of Hainan Medical University, Haikou, China;Department of Rheumatology, The First Affiliated Hospital of Hainan Medical University, Haikou, China;Hainan Provincial Key Laboratory for Human Reproductive Medicine and Genetic Research, Department of Reproductive Medicine, The First Affiliated Hospital of Hainan Medical University, Haikou, China;School of Medical Management, Hainan Medical University, Haikou, China;

关键词: subarachnoid hemorrhage;    early brain injury;    resveratrol;    PGC-1α;    mitochondrial biogenesis-function;   

DOI  :  10.3389/fmolb.2021.620683

来源: DOAJ

【 摘 要 】

Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) has been shown to play a pivotal role in the regulation of mitochondrial biogenesis in diseases. Resveratrol (RSV), a natural polyphenolic reagent, has powerful antioxidant properties and the ability to scavenge mitochondrial reactive oxygen species (ROS) in a variety of central nervous system diseases. However, the underlying molecular mechanisms of RSV on mitochondrial biogenesis in early brain injury (EBI) following subarachnoid hemorrhage (SAH) remain poorly understood. This study aimed to explore the potential neuroprotective effects of RSV on mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in a prechiasmatic cistern SAH model. PGC-1α expression and related mitochondrial biogenesis were detected. Amounts of nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (TFAM) were determined to evaluate the extent of mitochondrial biogenesis. Increased PGC-1α and mitochondrial biogenesis after SAH were observed in the temporal cortex. Resveratrol increased the expression of PGC-1α, NRF1, and TFAM, and promoted PGC-1α nuclear translocation. Moreover, RSV could scavenge excess ROS, increase the activity of superoxide dismutase (SOD), enhance the potential of mitochondrial membrane and ATP levels, reduce the number of mitochondrial DNA copy, and decrease the level of malondialdehyde (MDA). RSV significantly ameliorated the release of apoptosis-related cytokines, namely P53, cleaved caspase-3, cytochrome c, and BAX, leading to the amelioration of neuronal apoptosis, brain edema, and neurological impairment 24 h after SAH. These results indicate that resveratrol promotes mitochondrial biogenesis and function by activation of the PGC-1α signaling pathway in EBI following SAH.

【 授权许可】

Unknown