A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation

Mammalian skeletal muscle (SkM) tissue engages the Nrf2-Keap1-dependent antioxidant defense mechanism to respond adaptively to stress. Redox homeostasis mediated by the reversible modification of selective cysteines is the prevalent mode of regulation. The protein targets of SkM redox regulation are...

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Autores principales:	Rafay Abu, Li Yu, Ashok Kumar, Lie Gao, Vikas Kumar
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	Nrf2/Keap1 system skeletal muscle sedox cysteine quantitative proteomics IPA Genetics QH426-470
Acceso en línea:	https://doaj.org/article/06728d06c1824df38dc15c82956252ca
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spelling	oai:doaj.org-article:06728d06c1824df38dc15c82956252ca2021-11-25T17:40:17ZA Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation10.3390/genes121116552073-4425https://doaj.org/article/06728d06c1824df38dc15c82956252ca2021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4425/12/11/1655https://doaj.org/toc/2073-4425Mammalian skeletal muscle (SkM) tissue engages the Nrf2-Keap1-dependent antioxidant defense mechanism to respond adaptively to stress. Redox homeostasis mediated by the reversible modification of selective cysteines is the prevalent mode of regulation. The protein targets of SkM redox regulation are largely unknown. We previously reported the proteomic profiles of soleus (Sol) and extensor digitorum longus (EDL) with Nrf2 or Keap1 gene deletion, using SkM-specific Nrf2 or Keap1 knockout models; iMS-Nrf2flox/flox; and iMS-Keap1flox/flox. Here, we employed these two animal models to understand the global expression profile of red tibialis anterior (RTA) using a label free approach and its redox proteomics using iodoacetyl tandem mass tag (iodoTMT<sup>TM</sup>)-labeled cysteine quantitation. We quantified 298 proteins that were significantly altered globally in the RTA with Nrf2 deficiency but only 21 proteins in the Keap1 KO samples. These proteins are involved in four intracellular signaling pathways: sirtuin signaling, Nrf2 mediated oxidative stress response, oxidative phosphorylation, and mitochondrion dysfunction. Moreover, we identified and quantified the cysteine redox peptides of 34 proteins, which are associated with mitochondrial oxidative phosphorylation, energy metabolism, and extracellular matrix. Our findings suggest that Nrf2-deficient RTA is implicated in metabolic myopathy, mitochondrial disorders, and motor dysfunction, possibly due to an enhanced oxidative modification of the structure and functional proteins in skeletal myocytes.Rafay AbuLi YuAshok KumarLie GaoVikas KumarMDPI AGarticleNrf2/Keap1 systemskeletal musclesedox cysteinequantitative proteomicsIPAGeneticsQH426-470ENGenes, Vol 12, Iss 1655, p 1655 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nrf2/Keap1 system skeletal muscle sedox cysteine quantitative proteomics IPA Genetics QH426-470
spellingShingle	Nrf2/Keap1 system skeletal muscle sedox cysteine quantitative proteomics IPA Genetics QH426-470 Rafay Abu Li Yu Ashok Kumar Lie Gao Vikas Kumar A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
description	Mammalian skeletal muscle (SkM) tissue engages the Nrf2-Keap1-dependent antioxidant defense mechanism to respond adaptively to stress. Redox homeostasis mediated by the reversible modification of selective cysteines is the prevalent mode of regulation. The protein targets of SkM redox regulation are largely unknown. We previously reported the proteomic profiles of soleus (Sol) and extensor digitorum longus (EDL) with Nrf2 or Keap1 gene deletion, using SkM-specific Nrf2 or Keap1 knockout models; iMS-Nrf2flox/flox; and iMS-Keap1flox/flox. Here, we employed these two animal models to understand the global expression profile of red tibialis anterior (RTA) using a label free approach and its redox proteomics using iodoacetyl tandem mass tag (iodoTMT<sup>TM</sup>)-labeled cysteine quantitation. We quantified 298 proteins that were significantly altered globally in the RTA with Nrf2 deficiency but only 21 proteins in the Keap1 KO samples. These proteins are involved in four intracellular signaling pathways: sirtuin signaling, Nrf2 mediated oxidative stress response, oxidative phosphorylation, and mitochondrion dysfunction. Moreover, we identified and quantified the cysteine redox peptides of 34 proteins, which are associated with mitochondrial oxidative phosphorylation, energy metabolism, and extracellular matrix. Our findings suggest that Nrf2-deficient RTA is implicated in metabolic myopathy, mitochondrial disorders, and motor dysfunction, possibly due to an enhanced oxidative modification of the structure and functional proteins in skeletal myocytes.
format	article
author	Rafay Abu Li Yu Ashok Kumar Lie Gao Vikas Kumar
author_facet	Rafay Abu Li Yu Ashok Kumar Lie Gao Vikas Kumar
author_sort	Rafay Abu
title	A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
title_short	A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
title_full	A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
title_fullStr	A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
title_full_unstemmed	A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation
title_sort	quantitative proteomics approach to gain insight into nrf2-keap1 skeletal muscle system and its cysteine redox regulation
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/06728d06c1824df38dc15c82956252ca
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A Quantitative Proteomics Approach to Gain Insight into NRF2-KEAP1 Skeletal Muscle System and Its Cysteine Redox Regulation

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