{"title":"细胞外组蛋白对神经元细胞的毒性作用：线粒体功能障碍和凋亡。","authors":"Wei Cao, Jun Fang","doi":"10.1002/jbt.70477","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Extracellular histones, emerging as critical inflammatory mediators, have unclear yet significant implications in nerve injury. This study, through in vitro assays using PC-12 and SH-SY5Y neuronal cells, reveals the toxicological mechanisms of histones. Histones trigger calcium influx and disrupt mitochondrial function by opening the MPTP, resulting in a marked decline in MMP. This mitochondrial perturbation further leads to Cyt-C release and upregulation of Caspase-3, triggering apoptotic cell death. However, interventions with MgSO4 and CsA mitigate histone-induced toxicity by blocking calcium influx and inhibiting MPTP opening. These results enhance our understanding of histone-related neurotoxicity and may contribute to developing antidotes against histone-mediated nerve damage at the biochemical and molecular toxicology levels.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Toxic Effects of Extracellular Histones on Neuronal Cells: Mitochondrial Dysfunction and Apoptosis\",\"authors\":\"Wei Cao, Jun Fang\",\"doi\":\"10.1002/jbt.70477\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Extracellular histones, emerging as critical inflammatory mediators, have unclear yet significant implications in nerve injury. This study, through in vitro assays using PC-12 and SH-SY5Y neuronal cells, reveals the toxicological mechanisms of histones. Histones trigger calcium influx and disrupt mitochondrial function by opening the MPTP, resulting in a marked decline in MMP. This mitochondrial perturbation further leads to Cyt-C release and upregulation of Caspase-3, triggering apoptotic cell death. However, interventions with MgSO4 and CsA mitigate histone-induced toxicity by blocking calcium influx and inhibiting MPTP opening. These results enhance our understanding of histone-related neurotoxicity and may contribute to developing antidotes against histone-mediated nerve damage at the biochemical and molecular toxicology levels.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 9\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70477\",\"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":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70477","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Toxic Effects of Extracellular Histones on Neuronal Cells: Mitochondrial Dysfunction and Apoptosis
Extracellular histones, emerging as critical inflammatory mediators, have unclear yet significant implications in nerve injury. This study, through in vitro assays using PC-12 and SH-SY5Y neuronal cells, reveals the toxicological mechanisms of histones. Histones trigger calcium influx and disrupt mitochondrial function by opening the MPTP, resulting in a marked decline in MMP. This mitochondrial perturbation further leads to Cyt-C release and upregulation of Caspase-3, triggering apoptotic cell death. However, interventions with MgSO4 and CsA mitigate histone-induced toxicity by blocking calcium influx and inhibiting MPTP opening. These results enhance our understanding of histone-related neurotoxicity and may contribute to developing antidotes against histone-mediated nerve damage at the biochemical and molecular toxicology levels.
期刊介绍：
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.
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