Methodological Aspects of μLC-MS/MS for Wide-Scale Proteomic Analysis of Anthracycline-Induced Cardiomyopathy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F25%3A10498803" target="_blank" >RIV/00179906:_____/25:10498803 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11150/25:10498803

Výsledek na webu

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=359T3z4JTT" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=359T3z4JTT</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acsomega.4c09377" target="_blank" >10.1021/acsomega.4c09377</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Methodological Aspects of μLC-MS/MS for Wide-Scale Proteomic Analysis of Anthracycline-Induced Cardiomyopathy

Popis výsledku v původním jazyce

The efforts to utilize microflow liquid chromatography hyphenated to tandem mass spectrometry (mu LC-MS/MS) for deep-scale proteomic analysis are still growing. In this work, two-dimensional LC separation and peptide derivatization by a tandem mass tag (TMT) were used to assess the capability of mu LC-MS/MS to reveal protein changes associated with the severe chronic anthracycline cardiotoxicity phenotype in comparison with nanoflow liquid chromatography (nLC-MS/MS). The analysis of the control and anthracycline-treated rabbit myocardium by mu LC-MS/MS and nLC-MS/MS allowed quantification of 3956 and 4549 proteins, respectively, with 84% of these proteins shared in both data sets. Both nLC-MS/MS and mu LC-MS/MS revealed marked global proteome dysregulation in severe anthracycline cardiotoxicity, with a significant change in approximately 55% of all detected proteins. The mu LC-MS/MS analysis allowed less compressed and more precise determination of the TMT channel ratio and correspondingly broader fold-change protein distribution than nLC-MS/MS. The total number of significantly changed proteins was higher in nLC-MS/MS (2498 vs 2183, 1900 proteins shared), whereas the opposite was true for a number of significantly changed proteins with a fold-change cutoff &gt;= 2 (535 vs 820). The profound changes concerned mainly proteins of cardiomyocyte sarcomeres, costameres, intercalated discs, mitochondria, and extracellular matrix. In addition, distinct alterations in immune and defense response were found with a remarkable involvement of type I interferon signaling that has been recently hypothesized to be essential for anthracycline cardiotoxicity pathogenesis. Hence, mu LC-MS/MS was found to be a sound alternative to nLC-MS/MS that can be useful for comprehensive mapping of global myocardial proteome alterations such as those associated with severe anthracycline cardiotoxicity.

Název v anglickém jazyce

Methodological Aspects of μLC-MS/MS for Wide-Scale Proteomic Analysis of Anthracycline-Induced Cardiomyopathy

Popis výsledku anglicky

The efforts to utilize microflow liquid chromatography hyphenated to tandem mass spectrometry (mu LC-MS/MS) for deep-scale proteomic analysis are still growing. In this work, two-dimensional LC separation and peptide derivatization by a tandem mass tag (TMT) were used to assess the capability of mu LC-MS/MS to reveal protein changes associated with the severe chronic anthracycline cardiotoxicity phenotype in comparison with nanoflow liquid chromatography (nLC-MS/MS). The analysis of the control and anthracycline-treated rabbit myocardium by mu LC-MS/MS and nLC-MS/MS allowed quantification of 3956 and 4549 proteins, respectively, with 84% of these proteins shared in both data sets. Both nLC-MS/MS and mu LC-MS/MS revealed marked global proteome dysregulation in severe anthracycline cardiotoxicity, with a significant change in approximately 55% of all detected proteins. The mu LC-MS/MS analysis allowed less compressed and more precise determination of the TMT channel ratio and correspondingly broader fold-change protein distribution than nLC-MS/MS. The total number of significantly changed proteins was higher in nLC-MS/MS (2498 vs 2183, 1900 proteins shared), whereas the opposite was true for a number of significantly changed proteins with a fold-change cutoff &gt;= 2 (535 vs 820). The profound changes concerned mainly proteins of cardiomyocyte sarcomeres, costameres, intercalated discs, mitochondria, and extracellular matrix. In addition, distinct alterations in immune and defense response were found with a remarkable involvement of type I interferon signaling that has been recently hypothesized to be essential for anthracycline cardiotoxicity pathogenesis. Hence, mu LC-MS/MS was found to be a sound alternative to nLC-MS/MS that can be useful for comprehensive mapping of global myocardial proteome alterations such as those associated with severe anthracycline cardiotoxicity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30100 - Basic medicine

Projekt

<a href="/cs/project/EF18_069%2F0010046" target="_blank" >EF18_069/0010046: Předaplikační výzkum inovativních léčiv a medicínských technologií</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

ACS Omega

ISSN

2470-1343

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

12

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

14

Strana od-do

11980-11993

Kód UT WoS článku

001447295800001

EID výsledku v databázi Scopus

2-s2.0-105003037653