Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway
文献类型：期刊论文
| 作者 | Liu, Yang1,2,3 ; Yan, Jiawei1,2,3,4; Sun, Cao1,2,3; Li, Guo5; Li, Sirui5; Zhang, Luwei1,2,3; Di, Cuixia1,2,3; Gan, Lu1,2,3,4; Wang, Yupei1,2,3,4; Zhou, Rong1,2,3
|
| 刊名 | REDOX BIOLOGY
 |
| 出版日期 | 2018-07 |
| 卷号 | 17页码:143-157 |
| ISSN号 | 2213-2317 |
| 关键词 | Carbon ions Cognitive deficits NRF2 PINK1 Mitochondrial dysfunction Mitochondrial homeostasis Redox balance |
| DOI | 10.1016/j.redox.2018.04.012 |
| 英文摘要 | Carbon ion therapy is a promising modality in radiotherapy to treat tumors, however, a potential risk of induction of late normal tissue damage should still be investigated and protected. The aim of the present study was to explore the long-term cognitive deficits provoked by a high-linear energy transfer (high-LET) carbon ions in mice by targeting to hippocampus which plays a crucial role in memory and learning. Our data showed that, one month after 4 Gy carbon ion exposure, carbon ion irradiation conspicuously resulted in the impaired cognitive performance, neurodegeneration and neuronal cell death, as well as the reduced mitochondrial integrity, the disrupted activities of tricarboxylic acid cycle flux and electron transport chain, and the depressed antioxidant defense system, consequently leading to a decline of ATP production and persistent oxidative damage in the hippocampus region. Mechanistically, we demonstrated the disruptions of mitochondrial homeostasis and redox balance typically characterized by the disordered mitochondrial dynamics, mitophagy and glutathione redox couple, which is closely associated with the inhibitions of PINK1 and NRF2 signaling pathway as the key regulators of molecular responses in the context of neurotoxicity and neurodegenerative disorders. Most importantly, we found that administration with melatonin as a mitochondria-targeted antioxidant promoted the PINK1 accumulation on the mitochondrial membrane, and augmented the NRF2 accumulation and translocation. Moreover, melatonin pronouncedly enhanced the molecular interplay between NRF2 and PINK1. Furthermore, in the mouse hippocampal neuronal cells, overexpression of NRF2/PINK1 strikingly protected the hippocampal neurons from carbon ion-elicited toxic insults. Thus, these data suggest that alleviation of the sustained mitochondria! dysfunction and oxidative stress through co-modulation of NRF2 and PINK1 may be in charge of restoration of the cognitive impairments in a mouse model of high-LET carbon ion irradiation. |
| WOS关键词 | NEURAL-TUBE DEFECTS ; EARLY BRAIN-INJURY ; OXIDATIVE STRESS ; ALZHEIMERS-DISEASE ; NEURODEGENERATIVE DISEASES ; CELL-DEATH ; SUBARACHNOID HEMORRHAGE ; DOPAMINERGIC-NEURONS ; PARKINSONS-DISEASE ; IONIZING-RADIATION |
| 资助项目 | National Natural Science Foundation of China[U1432248] ; National Natural Science Foundation of China[11575262] ; National Natural Science Foundation of China[11675234] |
| WOS研究方向 | Biochemistry & Molecular Biology |
| 语种 | 英语 |
| 出版者 | ELSEVIER SCIENCE BV |
| WOS记录号 | WOS:000446792900012 |
| 源URL | [http://119.78.100.186/handle/113462/64392]  |
| 专题 | 中国科学院近代物理研究所 |
| 通讯作者 | Zhang, Hong |
| 作者单位 | 1.Chinese Acad Sci, Inst Modern Phys, Lanzhou 730000, Gansu, Peoples R China 2.Chinese Acad Sci, Key Lab Heavy Ion Radiat Med, Lanzhou 730000, Gansu, Peoples R China 3.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou 730000, Gansu, Peoples R China 4.Univ Chinese Acad Sci, Beijing 100039, Peoples R China 5.Lanzhou Univ, Lanzhou 730000, Gansu, Peoples R China |
| 推荐引用方式 GB/T 7714 | Liu, Yang,Yan, Jiawei,Sun, Cao,et al. Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway[J]. REDOX BIOLOGY,2018,17:143-157. |
| APA | Liu, Yang.,Yan, Jiawei.,Sun, Cao.,Li, Guo.,Li, Sirui.,...&Zhang, Hong.(2018).Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway.REDOX BIOLOGY,17,143-157. |
| MLA | Liu, Yang,et al."Ameliorating mitochondrial dysfunction restores carbon ion-induced cognitive deficits via co-activation of NRF2 and PINK1 signaling pathway".REDOX BIOLOGY 17(2018):143-157. |
入库方式： OAI收割
来源：近代物理研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。