{"title":"3-硝基酪氨酸通过抑制线粒体的运动缩短非多巴胺能神经元的轴突。","authors":"Masahiro Hirai , Kohei Suzuki , Yusuke Kassai , Yoshiyuki Konishi","doi":"10.1016/j.neuint.2024.105832","DOIUrl":null,"url":null,"abstract":"<div><p>3-Nitrotyrosine (3-NT), a byproduct of oxidative and nitrosative stress, is implicated in age-related neurodegenerative disorders. Current literature suggests that free 3-NT becomes integrated into the carboxy-terminal domain of α-tubulin via the tyrosination/detyrosination cycle. Independently of this integration, 3-NT has been associated with the cell death of dopaminergic neurons. Given the critical role of tyrosination/detyrosination in governing axonal morphology and function, the substitution of tyrosine with 3-NT in this process may potentially disrupt axonal homeostasis, although this aspect remains underexplored. In this study, we examined the impact of 3-NT on the axons of cerebellar granule neurons, which is used as a model for non-dopaminergic neurons. Our observations revealed axonal shortening, which correlated with the incorporation of 3-NT into α-tubulin. Importantly, this axonal effect was observed prior to the onset of cellular death. Furthermore, 3-NT was found to diminish mitochondrial motility within the axon, leading to a subsequent reduction in mitochondrial membrane potential. The suppression of syntaphilin, a protein responsible for anchoring mitochondria to microtubules, restored the mitochondrial motility and axonal elongation that were inhibited by 3-NT. These findings underscore the inhibitory role of 3-NT in axonal elongation by impeding mitochondrial movement, suggesting its potential involvement in axonal dysfunction within non-dopaminergic neurons.</p></div>","PeriodicalId":398,"journal":{"name":"Neurochemistry international","volume":null,"pages":null},"PeriodicalIF":4.4000,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0197018624001591/pdfft?md5=c622486016fb3db4a3f3635c1405a254&pid=1-s2.0-S0197018624001591-main.pdf","citationCount":"0","resultStr":"{\"title\":\"3-Nitrotyrosine shortens axons of non-dopaminergic neurons by inhibiting mitochondrial motility\",\"authors\":\"Masahiro Hirai , Kohei Suzuki , Yusuke Kassai , Yoshiyuki Konishi\",\"doi\":\"10.1016/j.neuint.2024.105832\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>3-Nitrotyrosine (3-NT), a byproduct of oxidative and nitrosative stress, is implicated in age-related neurodegenerative disorders. Current literature suggests that free 3-NT becomes integrated into the carboxy-terminal domain of α-tubulin via the tyrosination/detyrosination cycle. Independently of this integration, 3-NT has been associated with the cell death of dopaminergic neurons. Given the critical role of tyrosination/detyrosination in governing axonal morphology and function, the substitution of tyrosine with 3-NT in this process may potentially disrupt axonal homeostasis, although this aspect remains underexplored. In this study, we examined the impact of 3-NT on the axons of cerebellar granule neurons, which is used as a model for non-dopaminergic neurons. Our observations revealed axonal shortening, which correlated with the incorporation of 3-NT into α-tubulin. Importantly, this axonal effect was observed prior to the onset of cellular death. Furthermore, 3-NT was found to diminish mitochondrial motility within the axon, leading to a subsequent reduction in mitochondrial membrane potential. The suppression of syntaphilin, a protein responsible for anchoring mitochondria to microtubules, restored the mitochondrial motility and axonal elongation that were inhibited by 3-NT. These findings underscore the inhibitory role of 3-NT in axonal elongation by impeding mitochondrial movement, suggesting its potential involvement in axonal dysfunction within non-dopaminergic neurons.</p></div>\",\"PeriodicalId\":398,\"journal\":{\"name\":\"Neurochemistry international\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.4000,\"publicationDate\":\"2024-08-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0197018624001591/pdfft?md5=c622486016fb3db4a3f3635c1405a254&pid=1-s2.0-S0197018624001591-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Neurochemistry international\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0197018624001591\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Neurochemistry international","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0197018624001591","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
3-Nitrotyrosine shortens axons of non-dopaminergic neurons by inhibiting mitochondrial motility
3-Nitrotyrosine (3-NT), a byproduct of oxidative and nitrosative stress, is implicated in age-related neurodegenerative disorders. Current literature suggests that free 3-NT becomes integrated into the carboxy-terminal domain of α-tubulin via the tyrosination/detyrosination cycle. Independently of this integration, 3-NT has been associated with the cell death of dopaminergic neurons. Given the critical role of tyrosination/detyrosination in governing axonal morphology and function, the substitution of tyrosine with 3-NT in this process may potentially disrupt axonal homeostasis, although this aspect remains underexplored. In this study, we examined the impact of 3-NT on the axons of cerebellar granule neurons, which is used as a model for non-dopaminergic neurons. Our observations revealed axonal shortening, which correlated with the incorporation of 3-NT into α-tubulin. Importantly, this axonal effect was observed prior to the onset of cellular death. Furthermore, 3-NT was found to diminish mitochondrial motility within the axon, leading to a subsequent reduction in mitochondrial membrane potential. The suppression of syntaphilin, a protein responsible for anchoring mitochondria to microtubules, restored the mitochondrial motility and axonal elongation that were inhibited by 3-NT. These findings underscore the inhibitory role of 3-NT in axonal elongation by impeding mitochondrial movement, suggesting its potential involvement in axonal dysfunction within non-dopaminergic neurons.
期刊介绍:
Neurochemistry International is devoted to the rapid publication of outstanding original articles and timely reviews in neurochemistry. Manuscripts on a broad range of topics will be considered, including molecular and cellular neurochemistry, neuropharmacology and genetic aspects of CNS function, neuroimmunology, metabolism as well as the neurochemistry of neurological and psychiatric disorders of the CNS.