循环中的 N-乳酰氨基酸和 N-甲酰基蛋氨酸反映线粒体功能障碍并预测脓毒性休克的死亡率。

IF 3.5 3区 医学 Q2 ENDOCRINOLOGY & METABOLISM
Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha
{"title":"循环中的 N-乳酰氨基酸和 N-甲酰基蛋氨酸反映线粒体功能障碍并预测脓毒性休克的死亡率。","authors":"Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha","doi":"10.1007/s11306-024-02089-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.</p><p><strong>Objective: </strong>To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.</p><p><strong>Methods: </strong>We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.</p><p><strong>Results: </strong>Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.</p><p><strong>Conclusion: </strong>Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.</p>","PeriodicalId":18506,"journal":{"name":"Metabolomics","volume":null,"pages":null},"PeriodicalIF":3.5000,"publicationDate":"2024-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917846/pdf/","citationCount":"0","resultStr":"{\"title\":\"Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.\",\"authors\":\"Robert S Rogers, Rohit Sharma, Hardik B Shah, Owen S Skinner, Xiaoyan A Guo, Apekshya Panda, Rahul Gupta, Timothy J Durham, Kelsey B Shaughnessy, Jared R Mayers, Kathryn A Hibbert, Rebecca M Baron, B Taylor Thompson, Vamsi K Mootha\",\"doi\":\"10.1007/s11306-024-02089-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.</p><p><strong>Objective: </strong>To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.</p><p><strong>Methods: </strong>We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.</p><p><strong>Results: </strong>Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.</p><p><strong>Conclusion: </strong>Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.</p>\",\"PeriodicalId\":18506,\"journal\":{\"name\":\"Metabolomics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2024-03-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10917846/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Metabolomics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s11306-024-02089-z\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Metabolomics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s11306-024-02089-z","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0

摘要

导言:败血症是一种发病率很高的疾病,其特点是急性感染时炎症反应失调导致多器官功能障碍。线粒体功能障碍可能是败血症的发病机制之一,但线粒体功能障碍的量化仍然具有挑战性:目的:评估脓毒性休克时线粒体功能障碍循环标志物的增加程度及其与严重程度和死亡率的关系:我们对血浆进行了全扫描和靶向(已知的遗传线粒体疾病标志物)代谢组学研究,以确定线粒体功能障碍的标志物,这些标志物可将脓毒性休克患者(42 人)与无感染的心源性休克患者(19 人)、无败血症的菌血症患者(18 人)和非卧床对照组患者(19 人)区分开来--后三种情况下,线粒体功能(以外周耗氧量为指标)被认为是完好的:结果:与所有三个对照组相比,脓毒性休克患者体内有九种代谢物明显增加。其中包括线粒体蛋白翻译失调的标志物 N-甲酰基-L-蛋氨酸(f-Met)和 N-乳酰苯丙氨酸(lac-Phe),后者是 N-乳酰氨基酸(lac-AAs)的代表,在单基因线粒体疾病患者的血浆中会升高。与用于界定脓毒性休克的临床生物标志物乳酸盐相比,脓毒性休克存活者和非存活者之间在入院 24 小时内测量的 f-Met 和 lac-AAs 的差异更大。此外,与其他所有组别相比,色氨酸是脓毒性休克患者体内显著减少的代谢物,而其分解产物犬尿酸盐则是显著增加的9种代谢物之一:结论:未来的研究将lac-AAs和f-Met的测量与乳酸结合起来进行验证,从而确定以线粒体功能障碍为特征的脓毒症亚型。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.

Circulating N-lactoyl-amino acids and N-formyl-methionine reflect mitochondrial dysfunction and predict mortality in septic shock.

Introduction: Sepsis is a highly morbid condition characterized by multi-organ dysfunction resulting from dysregulated inflammation in response to acute infection. Mitochondrial dysfunction may contribute to sepsis pathogenesis, but quantifying mitochondrial dysfunction remains challenging.

Objective: To assess the extent to which circulating markers of mitochondrial dysfunction are increased in septic shock, and their relationship to severity and mortality.

Methods: We performed both full-scan and targeted (known markers of genetic mitochondrial disease) metabolomics on plasma to determine markers of mitochondrial dysfunction which distinguish subjects with septic shock (n = 42) from cardiogenic shock without infection (n = 19), bacteremia without sepsis (n = 18), and ambulatory controls (n = 19) - the latter three being conditions in which mitochondrial function, proxied by peripheral oxygen consumption, is presumed intact.

Results: Nine metabolites were significantly increased in septic shock compared to all three comparator groups. This list includes N-formyl-L-methionine (f-Met), a marker of dysregulated mitochondrial protein translation, and N-lactoyl-phenylalanine (lac-Phe), representative of the N-lactoyl-amino acids (lac-AAs), which are elevated in plasma of patients with monogenic mitochondrial disease. Compared to lactate, the clinical biomarker used to define septic shock, there was greater separation between survivors and non-survivors of septic shock for both f-Met and the lac-AAs measured within 24 h of ICU admission. Additionally, tryptophan was the one metabolite significantly decreased in septic shock compared to all other groups, while its breakdown product kynurenate was one of the 9 significantly increased.

Conclusion: Future studies which validate the measurement of lac-AAs and f-Met in conjunction with lactate could define a sepsis subtype characterized by mitochondrial dysfunction.

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
Metabolomics
Metabolomics 医学-内分泌学与代谢
CiteScore
6.60
自引率
2.80%
发文量
84
审稿时长
2 months
期刊介绍: Metabolomics publishes current research regarding the development of technology platforms for metabolomics. This includes, but is not limited to: metabolomic applications within man, including pre-clinical and clinical pharmacometabolomics for precision medicine metabolic profiling and fingerprinting metabolite target analysis metabolomic applications within animals, plants and microbes transcriptomics and proteomics in systems biology Metabolomics is an indispensable platform for researchers using new post-genomics approaches, to discover networks and interactions between metabolites, pharmaceuticals, SNPs, proteins and more. Its articles go beyond the genome and metabolome, by including original clinical study material together with big data from new emerging technologies.
×
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