DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle

Abstract

Protein S-glutathionylation is an important reversible post-translational modification implicated in redox signaling. Oxidative modifications to protein thiols can alter the activity of metabolic enzymes, transcription factors, kinases, phosphatases, and the function of contractile proteins. However, the extent to which muscle contraction induces oxidative modifications in redox sensitive thiols is not known. The purpose of this study was to determine the targets of S-glutathionylation redox signaling following fatiguing contractions. Anesthetized adult male CB6F1 (BALB/cBy × C57BL/6) mice were subjected to acute fatiguing contractions for 15 min using in vivo stimulations. The right (stimulated) and left (unstimulated) gastrocnemius muscleswere collected 60 min after the last stimulation and processed for redox proteomics assay of S-glutathionylation.

Authors:
 [1];  [2];  [2];  [2];  [1];  [1];  [2];  [1]
  1. Univ. of Washington, Seattle, WA (United States)
  2. Pacific Northwest National Lab. (PNNL), Richland, WA (United States)
Publication Date:
Research Org.:
Pacific Northwest National Laboratory (PNNL), Richland, WA (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1439099
Report Number(s):
PNNL-SA-135523
Journal ID: ISSN 2213-2317; PII: S2213231718303550
Grant/Contract Number:  
AC05-76RL01830
Resource Type:
Accepted Manuscript
Journal Name:
Redox Biology
Additional Journal Information:
Journal Volume: 17; Journal Issue: C; Journal ID: ISSN 2213-2317
Publisher:
Elsevier
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; Muscle contraction; Post-translational modification; S-glutathionylation; Redox signaling; Skeletal muscle; Thiol redox proteomics

Citation Formats

Kramer, Philip A., Duan, Jicheng, Gaffrey, Matthew J., Shukla, Anil K., Wang, Lu, Bammler, Theo K., Qian, Wei -Jun, and Marcinek, David J. Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle. United States: N. p., 2018. Web. doi:10.1016/j.redox.2018.05.011.
Kramer, Philip A., Duan, Jicheng, Gaffrey, Matthew J., Shukla, Anil K., Wang, Lu, Bammler, Theo K., Qian, Wei -Jun, & Marcinek, David J. Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle. United States. https://doi.org/10.1016/j.redox.2018.05.011
Kramer, Philip A., Duan, Jicheng, Gaffrey, Matthew J., Shukla, Anil K., Wang, Lu, Bammler, Theo K., Qian, Wei -Jun, and Marcinek, David J. Wed . "Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle". United States. https://doi.org/10.1016/j.redox.2018.05.011. https://www.osti.gov/servlets/purl/1439099.
@article{osti_1439099,
title = {Fatiguing contractions increase protein S-glutathionylation occupancy in mouse skeletal muscle},
author = {Kramer, Philip A. and Duan, Jicheng and Gaffrey, Matthew J. and Shukla, Anil K. and Wang, Lu and Bammler, Theo K. and Qian, Wei -Jun and Marcinek, David J.},
abstractNote = {Protein S-glutathionylation is an important reversible post-translational modification implicated in redox signaling. Oxidative modifications to protein thiols can alter the activity of metabolic enzymes, transcription factors, kinases, phosphatases, and the function of contractile proteins. However, the extent to which muscle contraction induces oxidative modifications in redox sensitive thiols is not known. The purpose of this study was to determine the targets of S-glutathionylation redox signaling following fatiguing contractions. Anesthetized adult male CB6F1 (BALB/cBy × C57BL/6) mice were subjected to acute fatiguing contractions for 15 min using in vivo stimulations. The right (stimulated) and left (unstimulated) gastrocnemius muscleswere collected 60 min after the last stimulation and processed for redox proteomics assay of S-glutathionylation.},
doi = {10.1016/j.redox.2018.05.011},
journal = {Redox Biology},
number = C,
volume = 17,
place = {United States},
year = {Wed May 23 00:00:00 EDT 2018},
month = {Wed May 23 00:00:00 EDT 2018}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 45 works
Citation information provided by
Web of Science

Figures / Tables:

Table 1 Table 1: Known glutathionylation sites associated with altered protein function. Table of P-SSG modifications significantly affected by fatiguing contractions sorted by Excitation/contraction Coupling, Metabolism, Redox Regulation, and Other. Significance determined by p-value (≤ 0.05). Note: Some P-SSG sites were no longer significant with FDR correction.

Save / Share:

Works referenced in this record:

The basics of thiols and cysteines in redox biology and chemistry
journal, March 2015


Cysteine Function Governs Its Conservation and Degeneration and Restricts Its Utilization on Protein Surfaces
journal, December 2010


The cysteine proteome
journal, July 2015


Glutathione and mitochondria
journal, July 2014

  • Ribas, Vicent; García-Ruiz, Carmen; Fernández-Checa, José C.
  • Frontiers in Pharmacology, Vol. 5
  • DOI: 10.3389/fphar.2014.00151

Causes and Consequences of Cysteine S -Glutathionylation
journal, July 2013

  • Grek, Christina L.; Zhang, Jie; Manevich, Yefim
  • Journal of Biological Chemistry, Vol. 288, Issue 37
  • DOI: 10.1074/jbc.R113.461368

Glutaredoxin: Role in Reversible Protein S -Glutathionylation and Regulation of Redox Signal Transduction and Protein Translocation
journal, March 2005

  • Shelton, Melissa D.; Chock, P. Boon; Mieyal, John J.
  • Antioxidants & Redox Signaling, Vol. 7, Issue 3-4
  • DOI: 10.1089/ars.2005.7.348

Molecular Mechanisms and Clinical Implications of Reversible Protein S -Glutathionylation
journal, November 2008

  • Mieyal, John J.; Gallogly, Molly M.; Qanungo, Suparna
  • Antioxidants & Redox Signaling, Vol. 10, Issue 11
  • DOI: 10.1089/ars.2008.2089

Protein S-glutathionylation: a regulatory device from bacteria to humans
journal, February 2009

  • Dalle-Donne, Isabella; Rossi, Ranieri; Colombo, Graziano
  • Trends in Biochemical Sciences, Vol. 34, Issue 2
  • DOI: 10.1016/j.tibs.2008.11.002

Xanthine oxidase inhibition attenuates skeletal muscle signaling following acute exercise but does not impair mitochondrial adaptations to endurance training
journal, April 2013

  • Wadley, G. D.; Nicolas, M. A.; Hiam, D. S.
  • American Journal of Physiology-Endocrinology and Metabolism, Vol. 304, Issue 8
  • DOI: 10.1152/ajpendo.00568.2012

Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production
journal, October 2008


Interactions Between Reactive Oxygen Species Generated by Contractile Activity and Aging in Skeletal Muscle?
journal, September 2013


Free radical generation by skeletal muscle of adult and old mice: effect of contractile activity
journal, April 2006


Impact of Oxidative Stress on Exercising Skeletal Muscle
journal, April 2015


Reactive Oxygen Species in Skeletal Muscle Signaling
journal, December 2012

  • Barbieri, Elena; Sestili, Piero
  • Journal of Signal Transduction, Vol. 2012
  • DOI: 10.1155/2012/982794

S-Glutathionylation signaling in cell biology: Progress and prospects
journal, August 2012


The Ability of Exercise-Associated Oxidative Stress to Trigger Redox-Sensitive Signalling Responses
journal, August 2017

  • Webb, Richard; Hughes, Michael; Thomas, Andrew
  • Antioxidants, Vol. 6, Issue 3
  • DOI: 10.3390/antiox6030063

Application of redox proteomics to skeletal muscle aging and exercise
journal, August 2014

  • McDonagh, Brian; Sakellariou, Giorgos K.; Jackson, Malcolm J.
  • Biochemical Society Transactions, Vol. 42, Issue 4
  • DOI: 10.1042/BST20140085

Differential Cysteine Labeling and Global Label-Free Proteomics Reveals an Altered Metabolic State in Skeletal Muscle Aging
journal, September 2014

  • McDonagh, Brian; Sakellariou, Giorgos K.; Smith, Neil T.
  • Journal of Proteome Research, Vol. 13, Issue 11
  • DOI: 10.1021/pr5006394

Redox-dependent increases in glutathione reductase and exercise preconditioning: role of NADPH oxidase and mitochondria
journal, January 2013

  • Frasier, Chad R.; Moukdar, Fatiha; Patel, Hetal D.
  • Cardiovascular Research, Vol. 98, Issue 1
  • DOI: 10.1093/cvr/cvt009

Antioxidants prevent health-promoting effects of physical exercise in humans
journal, May 2009

  • Ristow, M.; Zarse, K.; Oberbach, A.
  • Proceedings of the National Academy of Sciences, Vol. 106, Issue 21
  • DOI: 10.1073/pnas.0903485106

Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice
journal, June 2013

  • Siegel, Michael P.; Kruse, Shane E.; Percival, Justin M.
  • Aging Cell, Vol. 12, Issue 5
  • DOI: 10.1111/acel.12102

Targeting redox biology to reverse mitochondrial dysfunction
journal, August 2013


Ectopic Catalase Expression in Mitochondria by Adeno-Associated Virus Enhances Exercise Performance in Mice
journal, August 2009


Adaptive responses of mouse skeletal muscle to contractile activity: The effect of age
journal, November 2006

  • Vasilaki, A.; McArdle, F.; Iwanejko, L. M.
  • Mechanisms of Ageing and Development, Vol. 127, Issue 11
  • DOI: 10.1016/j.mad.2006.08.004

Molecular basis for an attenuated mitochondrial adaptive plasticity in aged skeletal muscle
journal, September 2009

  • Ljubicic, Vladimir; Joseph, Anna-Maria; Adhihetty, Peter J.
  • Aging, Vol. 1, Issue 9
  • DOI: 10.18632/aging.100083

Resin-assisted enrichment of thiols as a general strategy for proteomic profiling of cysteine-based reversible modifications
journal, December 2013


Crystal structures of MKK4 kinase domain reveal that substrate peptide binds to an allosteric site and induces an auto-inhibition state
journal, September 2010

  • Matsumoto, Takashi; Kinoshita, Takayoshi; Kirii, Yasuyuki
  • Biochemical and Biophysical Research Communications, Vol. 400, Issue 3
  • DOI: 10.1016/j.bbrc.2010.08.071

Architecture of Human Mitochondrial Respiratory Megacomplex I2III2IV2
journal, September 2017


Crystal structure of sarcoplasmic reticulum Ca2+-ATPase (SERCA) from bovine muscle
journal, April 2012

  • Sacchetto, Roberta; Bertipaglia, Ilenia; Giannetti, Sara
  • Journal of Structural Biology, Vol. 178, Issue 1
  • DOI: 10.1016/j.jsb.2012.02.008

Skeletal Muscle Fatigue: Cellular Mechanisms
journal, January 2008


Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene lists
journal, November 2008

  • Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.
  • Nucleic Acids Research, Vol. 37, Issue 1
  • DOI: 10.1093/nar/gkn923

Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
journal, December 2008

  • Huang, Da Wei; Sherman, Brad T.; Lempicki, Richard A.
  • Nature Protocols, Vol. 4, Issue 1
  • DOI: 10.1038/nprot.2008.211

Health benefits of physical activity: the evidence
journal, March 2006

  • Warburton, D. E. R.
  • Canadian Medical Association Journal, Vol. 174, Issue 6
  • DOI: 10.1503/cmaj.051351

Role of Exercise Therapy in Prevention of Decline in Aging Muscle Function: Glucocorticoid Myopathy and Unloading
journal, January 2012


Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions
journal, January 2014


Protein Glutathionylation in Cardiovascular Diseases
journal, October 2013

  • Pastore, Anna; Piemonte, Fiorella
  • International Journal of Molecular Sciences, Vol. 14, Issue 10
  • DOI: 10.3390/ijms141020845

The Giant Protein Titin: A Regulatory Node That Integrates Myocyte Signaling Pathways
journal, March 2011

  • Krüger, Martina; Linke, Wolfgang A.
  • Journal of Biological Chemistry, Vol. 286, Issue 12
  • DOI: 10.1074/jbc.R110.173260

S-Glutathionylation of Cryptic Cysteines Enhances Titin Elasticity by Blocking Protein Folding
journal, March 2014


Disulfide isomerization reactions in titin immunoglobulin domains enable a mode of protein elasticity
journal, January 2018


Identification of Cysteines Involved in S-Nitrosylation, S-Glutathionylation, and Oxidation to Disulfides in Ryanodine Receptor Type 1
journal, December 2006

  • Aracena-Parks, Paula; Goonasekera, Sanjeewa A.; Gilman, Charles P.
  • Journal of Biological Chemistry, Vol. 281, Issue 52
  • DOI: 10.1074/jbc.M600876200

Cross talk between Ca 2+ and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca 2+ release channels
journal, November 2005

  • Hidalgo, Cecilia
  • Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 360, Issue 1464
  • DOI: 10.1098/rstb.2005.1759

Hydrogen Peroxide–Mediated SERCA Cysteine 674 Oxidation Contributes to Impaired Cardiac Myocyte Relaxation in Senescent Mouse Heart
journal, August 2013

  • Qin, Fuzhong; Siwik, Deborah A.; Lancel, Steve
  • Journal of the American Heart Association, Vol. 2, Issue 4
  • DOI: 10.1161/JAHA.113.000184

Mechanism of ATP-sensitive K Channel Inhibition by Sulfhydryl Modification
journal, September 1998

  • Trapp, Stefan; Tucker, Stephen J.; Ashcroft, Frances M.
  • Journal of General Physiology, Vol. 112, Issue 3
  • DOI: 10.1085/jgp.112.3.325

How mitochondria produce reactive oxygen species
journal, December 2008


Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism
journal, June 2015

  • Liemburg-Apers, Dania C.; Willems, Peter H. G. M.; Koopman, Werner J. H.
  • Archives of Toxicology, Vol. 89, Issue 8
  • DOI: 10.1007/s00204-015-1520-y

Mitochondrial Glutathione, a Key Survival Antioxidant
journal, November 2009

  • Marí, Montserrat; Morales, Albert; Colell, Anna
  • Antioxidants & Redox Signaling, Vol. 11, Issue 11
  • DOI: 10.1089/ars.2009.2695

S-glutathionylation of glyceraldehyde-3-phosphate dehydrogenase induces formation of C150-C154 intrasubunit disulfide bond in the active site of the enzyme
journal, December 2017

  • Barinova, K. V.; Serebryakova, M. V.; Muronetz, V. I.
  • Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1861, Issue 12
  • DOI: 10.1016/j.bbagen.2017.09.008

Posttranslational Modification of Glyceraldehyde-3-phosphate Dehydrogenase by S-Nitrosylation and Subsequent NADH Attachment
journal, February 1996

  • Mohr, Susanne; Stamler, Jonathan S.; Brüne, Bernhard
  • Journal of Biological Chemistry, Vol. 271, Issue 8
  • DOI: 10.1074/jbc.271.8.4209

Glyceraldehyde Phosphate Dehydrogenase Oxidation During Cardiac Ischemia and Reperfusion
journal, November 2002

  • Eaton, Philip; Wright, Neville; Hearse, David J.
  • Journal of Molecular and Cellular Cardiology, Vol. 34, Issue 11
  • DOI: 10.1006/jmcc.2002.2108

Isotope-Coded Affinity Tag (ICAT) Approach to Redox Proteomics:  Identification and Quantitation of Oxidant-Sensitive Cysteine Thiols in Complex Protein Mixtures
journal, December 2004

  • Sethuraman, Mahadevan; McComb, Mark E.; Huang, Hua
  • Journal of Proteome Research, Vol. 3, Issue 6
  • DOI: 10.1021/pr049887e

Inactivation of creatine kinase by S-glutathionylation of the active-site cysteine residue
journal, April 2000

  • Reddy, Sharanya; Jones, A. Daniel; Cross, Carroll E.
  • Biochemical Journal, Vol. 347, Issue 3
  • DOI: 10.1042/bj3470821

Quantitative Analysis of Redox-Sensitive Proteome with DIGE and ICAT
journal, August 2008

  • Fu, Cexiong; Hu, Jun; Liu, Tong
  • Journal of Proteome Research, Vol. 7, Issue 9
  • DOI: 10.1021/pr800233r

S-glutathionylation reactions in mitochondrial function and disease
journal, November 2014

  • Mailloux, Ryan J.; Willmore, William G.
  • Frontiers in Cell and Developmental Biology, Vol. 2
  • DOI: 10.3389/fcell.2014.00068

Sites and Mechanisms of Aconitase Inactivation by Peroxynitrite:  Modulation by Citrate and Glutathione
journal, August 2005

  • Han, Derick; Canali, Raffaella; Garcia, Jerome
  • Biochemistry, Vol. 44, Issue 36
  • DOI: 10.1021/bi0509393

Redox proteomics of thiol proteins in mouse heart during ischemia/reperfusion using ICAT reagents and mass spectrometry
journal, May 2013


Glutaredoxin-2 Is Required to Control Oxidative Phosphorylation in Cardiac Muscle by Mediating Deglutathionylation Reactions
journal, April 2014

  • Mailloux, Ryan J.; Xuan, Jian Ying; McBride, Skye
  • Journal of Biological Chemistry, Vol. 289, Issue 21
  • DOI: 10.1074/jbc.M114.550574

Protein S-glutathionlyation links energy metabolism to redox signaling in mitochondria
journal, August 2016


Mass Spectrometry Profiles Superoxide-Induced Intramolecular Disulfide in the FMN-Binding Subunit of Mitochondrial Complex I
journal, December 2008

  • Zhang, L.; Xu, H.; Chen, C.
  • Journal of the American Society for Mass Spectrometry, Vol. 19, Issue 12
  • DOI: 10.1016/j.jasms.2008.08.004

Site-Specific S-Glutathiolation of Mitochondrial NADH Ubiquinone Reductase
journal, April 2007

  • Chen, Chwen-Lih; Zhang, Liwen; Yeh, Alexander
  • Biochemistry, Vol. 46, Issue 19
  • DOI: 10.1021/bi602580c

Quantitative Mapping of Reversible Mitochondrial Complex I Cysteine Oxidation in a Parkinson Disease Mouse Model
journal, January 2011

  • Danielson, Steven R.; Held, Jason M.; Oo, May
  • Journal of Biological Chemistry, Vol. 286, Issue 9
  • DOI: 10.1074/jbc.M110.190108

Fatty acid nitroalkenes induce resistance to ischemic cardiac injury by modulating mitochondrial respiration at complex II
journal, August 2016


Mitochondrial Complex II in the Post-ischemic Heart
journal, November 2007

  • Chen, Yeong-Renn; Chen, Chwen-Lih; Pfeiffer, Douglas R.
  • Journal of Biological Chemistry, Vol. 282, Issue 45
  • DOI: 10.1074/jbc.M702294200

S- Sulfhydration of ATP synthase by hydrogen sulfide stimulates mitochondrial bioenergetics
journal, November 2016


Redox Regulation of Mitochondrial ATP Synthase
journal, January 2013

  • Wang, Sheng-Bing; Murray, Christopher I.; Chung, Heaseung S.
  • Trends in Cardiovascular Medicine, Vol. 23, Issue 1
  • DOI: 10.1016/j.tcm.2012.08.005

14-3-3gamma Interacts with and Is Phosphorylated by Multiple Protein Kinase C Isoforms in PDGF-Stimulated Human Vascular Smooth Muscle Cells
journal, July 1999


Unlocking the code of 14-3-3
journal, April 2004

  • Dougherty, Michele K.; Morrison, Deborah K.
  • Journal of Cell Science, Vol. 117, Issue 10
  • DOI: 10.1242/jcs.01171

Mitogen-Activated Protein Kinases and Reactive Oxygen Species: How Can ROS Activate MAPK Pathways?
journal, February 2011

  • Son, Yong; Cheong, Yong-Kwan; Kim, Nam-Ho
  • Journal of Signal Transduction, Vol. 2011
  • DOI: 10.1155/2011/792639

Organization of Iron-Sulfur Clusters in Respiratory Complex I
journal, July 2005


Quantitative proteomic characterization of redox-dependent post-translational modifications on protein cysteines
journal, January 2017

  • Duan, Jicheng; Gaffrey, Matthew J.; Qian, Wei-Jun
  • Molecular BioSystems, Vol. 13, Issue 5
  • DOI: 10.1039/C6MB00861E

Redox Biology: Computational Approaches to the Investigation of Functional Cysteine Residues
journal, July 2011

  • Marino, Stefano M.; Gladyshev, Vadim N.
  • Antioxidants & Redox Signaling, Vol. 15, Issue 1
  • DOI: 10.1089/ars.2010.3561

Works referencing / citing this record:

Increase in muscle power is associated with myofibrillar ATPase adaptations during resistance training
journal, May 2019

  • Philippe, Antony G.; Lionne, Corinne; Sanchez, Anthony M. J.
  • Experimental Physiology, Vol. 104, Issue 8
  • DOI: 10.1113/ep087071

Mitoproteomics: Tackling Mitochondrial Dysfunction in Human Disease
journal, November 2018

  • Gómez-Serrano, María; Camafeita, Emilio; Loureiro, Marta
  • Oxidative Medicine and Cellular Longevity, Vol. 2018
  • DOI: 10.1155/2018/1435934

Isotopically Labeled Clickable Glutathione to Quantify Protein S‐Glutathionylation
journal, October 2019

  • VanHecke, Garrett C.; Yapa Abeywardana, Maheeshi; Huang, Bo
  • ChemBioChem, Vol. 21, Issue 6
  • DOI: 10.1002/cbic.201900528

Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2
journal, July 2019


Mitoproteomics: Tackling Mitochondrial Dysfunction in Human Disease
journal, November 2018

  • Gómez-Serrano, María; Camafeita, Emilio; Loureiro, Marta
  • Oxidative Medicine and Cellular Longevity, Vol. 2018
  • DOI: 10.1155/2018/1435934

Sex-dependent Differences in the Bioenergetics of Liver and Muscle Mitochondria from Mice Containing a Deletion for glutaredoxin-2
journal, July 2019


Physical Activity and Brain Health
journal, September 2019


Figures/Tables have been extracted from DOE-funded journal article accepted manuscripts.