Cargando…

Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy

Nuclear factor erythroid 2-related factor 2 (NRF2), a redox sensor, is vital for cellular redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2-TG) exhibit reductive stress (RS). In this study, we identified novel protein signature for RS-induced cardiomyo...

Descripción completa

Detalles Bibliográficos
Autores principales: Sunny, Sini, Jyothidasan, Arun, David, Cynthia L., Parsawar, Krishna, Veerappan, Arul, Jones, Dean P., Pogwizd, Steven, Rajasekaran, Namakkal S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234166/
https://www.ncbi.nlm.nih.gov/pubmed/35770227
http://dx.doi.org/10.3389/fcvm.2022.848045
_version_ 1784735998171676672
author Sunny, Sini
Jyothidasan, Arun
David, Cynthia L.
Parsawar, Krishna
Veerappan, Arul
Jones, Dean P.
Pogwizd, Steven
Rajasekaran, Namakkal S.
author_facet Sunny, Sini
Jyothidasan, Arun
David, Cynthia L.
Parsawar, Krishna
Veerappan, Arul
Jones, Dean P.
Pogwizd, Steven
Rajasekaran, Namakkal S.
author_sort Sunny, Sini
collection PubMed
description Nuclear factor erythroid 2-related factor 2 (NRF2), a redox sensor, is vital for cellular redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2-TG) exhibit reductive stress (RS). In this study, we identified novel protein signature for RS-induced cardiomyopathy using Tandem Mass Tag (TMT) proteomic analysis in heart tissues of TG (CaNrf2-TG) mice at 6–7 months of age. A total of 1,105 proteins were extracted from 22,544 spectra. About 560 proteins were differentially expressed in TG vs. NTg hearts, indicating a global impact of RS on the myocardial proteome. Over 32 proteins were significantly altered in response to RS -20 were upregulated and 12 were downregulated in the hearts of TG vs. NTg mice, suggesting that these proteins could be putative signatures of RS. Scaffold analysis revealed a clear distinction between TG vs. NTg hearts. The majority of the differentially expressed proteins (DEPs) that were significantly altered in RS mice were found to be involved in stress related pathways such as antioxidants, NADPH, protein quality control, etc. Interestingly, proteins that were involved in mitochondrial respiration, lipophagy and cardiac rhythm were dramatically decreased in TG hearts. Of note, we identified the glutathione family of proteins as the significantly changed subset of the proteome in TG heart. Surprisingly, our comparative analysis of NGS based transcriptome and TMT-proteome indicated that ~50% of the altered proteins in TG myocardium was found to be negatively correlated with their transcript levels. In association with the altered proteome the TG mice displayed pathological cardiac remodeling.
format Online
Article
Text
id pubmed-9234166
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-92341662022-06-28 Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy Sunny, Sini Jyothidasan, Arun David, Cynthia L. Parsawar, Krishna Veerappan, Arul Jones, Dean P. Pogwizd, Steven Rajasekaran, Namakkal S. Front Cardiovasc Med Cardiovascular Medicine Nuclear factor erythroid 2-related factor 2 (NRF2), a redox sensor, is vital for cellular redox homeostasis. We reported that transgenic mice expressing constitutively active Nrf2 (CaNrf2-TG) exhibit reductive stress (RS). In this study, we identified novel protein signature for RS-induced cardiomyopathy using Tandem Mass Tag (TMT) proteomic analysis in heart tissues of TG (CaNrf2-TG) mice at 6–7 months of age. A total of 1,105 proteins were extracted from 22,544 spectra. About 560 proteins were differentially expressed in TG vs. NTg hearts, indicating a global impact of RS on the myocardial proteome. Over 32 proteins were significantly altered in response to RS -20 were upregulated and 12 were downregulated in the hearts of TG vs. NTg mice, suggesting that these proteins could be putative signatures of RS. Scaffold analysis revealed a clear distinction between TG vs. NTg hearts. The majority of the differentially expressed proteins (DEPs) that were significantly altered in RS mice were found to be involved in stress related pathways such as antioxidants, NADPH, protein quality control, etc. Interestingly, proteins that were involved in mitochondrial respiration, lipophagy and cardiac rhythm were dramatically decreased in TG hearts. Of note, we identified the glutathione family of proteins as the significantly changed subset of the proteome in TG heart. Surprisingly, our comparative analysis of NGS based transcriptome and TMT-proteome indicated that ~50% of the altered proteins in TG myocardium was found to be negatively correlated with their transcript levels. In association with the altered proteome the TG mice displayed pathological cardiac remodeling. Frontiers Media S.A. 2022-06-13 /pmc/articles/PMC9234166/ /pubmed/35770227 http://dx.doi.org/10.3389/fcvm.2022.848045 Text en Copyright © 2022 Sunny, Jyothidasan, David, Parsawar, Veerappan, Jones, Pogwizd and Rajasekaran. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Sunny, Sini
Jyothidasan, Arun
David, Cynthia L.
Parsawar, Krishna
Veerappan, Arul
Jones, Dean P.
Pogwizd, Steven
Rajasekaran, Namakkal S.
Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title_full Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title_fullStr Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title_full_unstemmed Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title_short Tandem Mass Tagging Based Identification of Proteome Signatures for Reductive Stress Cardiomyopathy
title_sort tandem mass tagging based identification of proteome signatures for reductive stress cardiomyopathy
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9234166/
https://www.ncbi.nlm.nih.gov/pubmed/35770227
http://dx.doi.org/10.3389/fcvm.2022.848045
work_keys_str_mv AT sunnysini tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT jyothidasanarun tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT davidcynthial tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT parsawarkrishna tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT veerappanarul tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT jonesdeanp tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT pogwizdsteven tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy
AT rajasekarannamakkals tandemmasstaggingbasedidentificationofproteomesignaturesforreductivestresscardiomyopathy