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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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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 |
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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 |
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