期刊
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY
卷 2022, 期 -, 页码 -出版社
HINDAWI LTD
DOI: 10.1155/2022/6298786
关键词
-
类别
In rat hippocampal neurons, hypoxia leads to mitochondrial abnormalities and oxidative stress, resulting in reduced neuron viability. However, propofol protects against mitochondrial dysfunction and preserves neuron viability through its antioxidant properties. This protection is mediated by HIF-1α-induced expression of Drp1 and ERK/PKA-mediated phosphorylation of Drp1.
Background. Hypoxia may induce mitochondrial abnormality, which is associated with a variety of clinical phenotypes in the central nervous system. Propofol is an anesthetic agent with neuroprotective property. We examined whether and how propofol protected hypoxia-induced mitochondrial abnormality in neurons. Methods. Primary rat hippocampal neurons were exposed to propofol followed by hypoxia treatment. Neuron viability, mitochondrial morphology, mitochondrial permeability transition pore (mPTP) opening, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) production were measured. Mechanisms including reactive oxygen species (ROS), extracellular regulated protein kinase (ERK), protein kinase A (PKA), HIF-1 alpha, Drp1, Fis1, Mfn1, Mfn2, and Opa1 were investigated. Results. Hypoxia increased intracellular ROS production and induced mPTP opening, while reducing ATP production, MMP values, and neuron viability. Hypoxia impaired mitochondrial dynamic balance by increasing mitochondrial fragmentation. Further, hypoxia induced the translocation of HIF-1 alpha and increased the expression of Drp1, while having no effect on Fis1 expression. In addition, hypoxia induced the phosphorylation of ERK and Drp1(ser616), while reducing the phosphorylation of PKA and Drp1(ser637). Importantly, we demonstrated all these effects were attenuated by pretreatment of neurons with 50 mu M propofol, antioxidant alpha-tocopherol, and ROS scavenger ebselen. Besides, hypoxia, propofol, alpha-tocopherol, or ebselen had no effect on the expression of Mfn1, Mfn2, and Opa1. Conclusions. In rat hippocampal neurons, hypoxia induced oxidative stress, caused mitochondrial dynamic imbalance and malfunction, and reduced neuron viability. Propofol protected mitochondrial abnormality and neuron viability via antioxidant property, and the molecular mechanisms involved HIF-1 alpha-mediated Drp1 expression and ERK/PKA-mediated Drp1 phosphorylation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据