期刊
EXPERIMENTAL NEUROBIOLOGY
卷 30, 期 1, 页码 73-86出版社
KOREAN SOC BRAIN & NEURAL SCIENCE, KOREAN SOC NEURODEGENERATIVE DISEASE
DOI: 10.5607/en20051
关键词
Nobiletin; Mitochondria; Electron transport chains; Complex I; ROS,Apoptosis-inducing factor
资金
- Jeju National University Hospital Research Fund of Jeju National University
The study found that nobiletin regulates mitochondrial function by inhibiting complex I (CI) rather than complex III (CIII), reducing oxidative stress, inhibiting apoptotic signaling, and enhancing ATP production, thus restoring neuronal viability. These effects can be attributed to the downregulation of apoptosis-induced factor (AIF) by nobiletin and the upregulation of antioxidant enzymes such as Nrf2 and HO-1.
Nobiletin, a polymethoxylated flavonoid found in citrus, has been studied because of its modulatory functions in cellular signaling cascades, and effects to prevent mitochondrial calcium overload and neuronal cell death. Particularly, we previously reported that nobiletin induced changes in the mitochondrial membrane potential through K+ channel regulation, suggesting that nobiletin might exert neuroprotective effects via regulating mitochondrial functions associated with the electron transport chain (ETC) system. This study investigated whether nobiletin regulated mitochondrial dysfunction mediated by ETC system downregulation by inhibiting complex I (CI) and complex III (CIII) in pure mitochondria and the cortical neurons of rats. The results showed that nobiletin significantly reduced mitochondrial reactive oxygen species (ROS) production, inhibited apoptotic signaling, enhanced ATP production and then restored neuronal viability under conditions of CI inhibition, but not CIII inhibition. These effects were attributed to the downregulation of translocation of apoptosis-induced factor (AIF), and the upregulation of CI activity and the expression of antioxidant enzymes such as Nrf2 and HO-1. Together with our previous study, these results indicate that the neuroprotective effects of nobiletin under mitochondrial dysfunction may be associated with its function to activate antioxidant signaling cascades. Our findings suggest the possibility that nobiletin has therapeutic potential in treating oxidative neurological and neurodegenerative diseases mediated by mitochondrial dysfunction.
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