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Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes
Increased secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), is often associated with adipose tissue dysregulation, which often accompanies obesity. High levels of TNFα have been linked to the development of insulin resistance in several tissues and organs, including...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464716/ https://www.ncbi.nlm.nih.gov/pubmed/34576943 http://dx.doi.org/10.3390/molecules26185472 |
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author | Mohallem, Rodrigo Aryal, Uma K. |
author_facet | Mohallem, Rodrigo Aryal, Uma K. |
author_sort | Mohallem, Rodrigo |
collection | PubMed |
description | Increased secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), is often associated with adipose tissue dysregulation, which often accompanies obesity. High levels of TNFα have been linked to the development of insulin resistance in several tissues and organs, including skeletal muscle and the liver. In this study, we examined the complex regulatory roles of TNFα in murine hepatocytes utilizing a combination of global proteomic and phosphoproteomic analyses. Our results show that TNFα promotes extensive changes not only of protein levels, but also the dynamics of their downstream phosphorylation signaling. We provide evidence that TNFα induces DNA replication and promotes G1/S transition through activation of the MAPK pathway. Our data also highlight several other novel proteins, many of which are regulated by phosphorylation and play a role in the progression and development of insulin resistance in hepatocytes. |
format | Online Article Text |
id | pubmed-8464716 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84647162021-09-27 Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes Mohallem, Rodrigo Aryal, Uma K. Molecules Article Increased secretion of proinflammatory cytokines, such as tumor necrosis factor-alpha (TNFα), is often associated with adipose tissue dysregulation, which often accompanies obesity. High levels of TNFα have been linked to the development of insulin resistance in several tissues and organs, including skeletal muscle and the liver. In this study, we examined the complex regulatory roles of TNFα in murine hepatocytes utilizing a combination of global proteomic and phosphoproteomic analyses. Our results show that TNFα promotes extensive changes not only of protein levels, but also the dynamics of their downstream phosphorylation signaling. We provide evidence that TNFα induces DNA replication and promotes G1/S transition through activation of the MAPK pathway. Our data also highlight several other novel proteins, many of which are regulated by phosphorylation and play a role in the progression and development of insulin resistance in hepatocytes. MDPI 2021-09-08 /pmc/articles/PMC8464716/ /pubmed/34576943 http://dx.doi.org/10.3390/molecules26185472 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Mohallem, Rodrigo Aryal, Uma K. Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title | Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title_full | Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title_fullStr | Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title_full_unstemmed | Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title_short | Quantitative Proteomics and Phosphoproteomics Reveal TNF-α-Mediated Protein Functions in Hepatocytes |
title_sort | quantitative proteomics and phosphoproteomics reveal tnf-α-mediated protein functions in hepatocytes |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8464716/ https://www.ncbi.nlm.nih.gov/pubmed/34576943 http://dx.doi.org/10.3390/molecules26185472 |
work_keys_str_mv | AT mohallemrodrigo quantitativeproteomicsandphosphoproteomicsrevealtnfamediatedproteinfunctionsinhepatocytes AT aryalumak quantitativeproteomicsandphosphoproteomicsrevealtnfamediatedproteinfunctionsinhepatocytes |