在肌营养不良症肌肉细胞模型中补充油酸的治疗潜力。

IF 4.3 2区 生物学 Q1 BIOLOGY
Nerea Moreno, Maria Sabater-Arcis, Teresa Sevilla, Manuel Perez Alonso, Jessica Ohana, Ariadna Bargiela, Ruben Artero
{"title":"在肌营养不良症肌肉细胞模型中补充油酸的治疗潜力。","authors":"Nerea Moreno, Maria Sabater-Arcis, Teresa Sevilla, Manuel Perez Alonso, Jessica Ohana, Ariadna Bargiela, Ruben Artero","doi":"10.1186/s40659-024-00496-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.</p><p><strong>Results: </strong>We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts.</p><p><strong>Conclusions: </strong>For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100173/pdf/","citationCount":"0","resultStr":"{\"title\":\"Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.\",\"authors\":\"Nerea Moreno, Maria Sabater-Arcis, Teresa Sevilla, Manuel Perez Alonso, Jessica Ohana, Ariadna Bargiela, Ruben Artero\",\"doi\":\"10.1186/s40659-024-00496-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.</p><p><strong>Results: </strong>We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts.</p><p><strong>Conclusions: </strong>For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.</p>\",\"PeriodicalId\":9084,\"journal\":{\"name\":\"Biological Research\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-05-17\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11100173/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Research\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s40659-024-00496-z\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s40659-024-00496-z","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

背景:我们最近报告说,在罕见的神经肌肉疾病肌营养不良症1型中,Musashi 2(MSI2)蛋白的上调通过降低miR-7的水平导致肌肉分解代谢过程自噬和UPS的过度激活。由于油酸(OA)是miR-7生物生成过程中MSI2活性的已知异构调节剂,我们在此试图评估这种脂肪酸的内源性水平及其在体外挽救细胞分化表型方面的治疗潜力。在这项工作中,我们用OA处理了来自DM1患者的四种肌肉细胞系24小时,并分析了自噬和肌肉分化参数:结果:我们发现在不同的疾病细胞模型中,OA的水平都有所下降。结果:我们发现,在不同的疾病细胞模型中,OA水平都有所下降,补充OA后,疾病相关表型(如融合指数、肌管直径)得到改善,自噬功能受到抑制。这涉及抑制MSI2对直接分子靶标miR-7的调控,因为OA异构体麦饭石酸(EA)不能产生同样的挽救效果。OA水平的降低似乎源于生物生成受损,因为在DM1中,负责将硬脂酸转化为油酸的硬脂酰-CoA脱饱和酶1(SCD1)的水平降低,并与OA数量相关:我们首次在 DM1 中描述了脂肪酸代谢障碍,这种障碍至少部分源于 SCD1 的减少。由于OA会异位抑制MSI2与分子靶标的结合,因此OA水平的降低会与MSI2的过度表达产生协同作用,并促成MSI2 > miR-7 > 自噬轴,我们提出了这一轴来解释肌肉萎缩表型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Therapeutic potential of oleic acid supplementation in myotonic dystrophy muscle cell models.

Background: We recently reported that upregulation of Musashi 2 (MSI2) protein in the rare neuromuscular disease myotonic dystrophy type 1 contributes to the hyperactivation of the muscle catabolic processes autophagy and UPS through a reduction in miR-7 levels. Because oleic acid (OA) is a known allosteric regulator of MSI2 activity in the biogenesis of miR-7, here we sought to evaluate endogenous levels of this fatty acid and its therapeutic potential in rescuing cell differentiation phenotypes in vitro. In this work, four muscle cell lines derived from DM1 patients were treated with OA for 24 h, and autophagy and muscle differentiation parameters were analyzed.

Results: We demonstrate a reduction of OA levels in different cell models of the disease. OA supplementation rescued disease-related phenotypes such as fusion index, myotube diameter, and repressed autophagy. This involved inhibiting MSI2 regulation of direct molecular target miR-7 since OA isoschizomer, elaidic acid (EA) could not cause the same rescues. Reduction of OA levels seems to stem from impaired biogenesis since levels of the enzyme stearoyl-CoA desaturase 1 (SCD1), responsible for converting stearic acid to oleic acid, are decreased in DM1 and correlate with OA amounts.

Conclusions: For the first time in DM1, we describe a fatty acid metabolism impairment that originated, at least in part, from a decrease in SCD1. Because OA allosterically inhibits MSI2 binding to molecular targets, reduced OA levels synergize with the overexpression of MSI2 and contribute to the MSI2 > miR-7 > autophagy axis that we proposed to explain the muscle atrophy phenotype.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信