Aerobic Exercises Induce Antioxidant Pathways Activation in Rats

Najmeh Barghi, Effat Bambaeichi, Mostafa Rezaei‑Tavirani, Neda Khaledi

Abstract


Background: Aerobic exercises induce adaptations that improve physiological function. However, aerobic exercises, oxidative reproduction may lead to injury and other health issues such as adverse cardiac effects. The aim of this study is to evaluate the effect of aerobic exercises on protein expression change in the heart left ventricle to determine the advantages and disadvantages related to this mode of exercise.

Methods: Male Wistar rats were randomized into two groups; trained (T) and control (C). Animals from T group were trained for 8 weeks, and then 2D LC‑MS/MS iTRAQ method was used for extracting and analyzing the left ventricular proteins. Certain proteins that were highlighted in the special process were selected for further analysis via protein‑protein interaction network (PPI) method. The identified proteins were enriched via gene ontology (GO) to find biological terms.

Results: We identify five overexpressed antioxidant proteins in T group compared with C group including extracellular superoxide dismutase [Cu‑Zn], Frataxin, protein kinase C delta type, STE20/SPS1‑related proline‑alanine‑rich protein kinase, and amyloid‑beta A4 protein.

Conclusions: Findings indicate that catalase and insulin are two exercise‑related proteins. However, they were not included in the significant differentially expressed proteins. Finally it was found that enhancement of antioxidative activity is a direct effect of aerobic exercises.


Keywords


Antioxidants; exercise therapy; heart ventricles; oxidative stress; proteomics

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References


Mohammadi HR, Khoshnam MS, Khoshnam E. Effects of

different modes of exercise training on body composition and

risk factors for cardiovascular disease in middle‑aged men. Int J

Prev Med 2018;9:9.

Warburton DE, Nicol CW, Bredin SS. Health benefits of physical

activity: The evidence. CMAJ 2006;174:801‑9.

Powers SK, Jackson MJ. Exercise‑induced oxidative stress:

Cellular mechanisms and impact on muscle force production.

Physiol Rev 2008;88:1243‑76.

Chandra K, Salman AS, Mohd A, Sweety R, Ali KN. Protection

against FCA induced oxidative stress induced DNA damage

as a model of arthritis and in vitro anti‑arthritic potential of

costus speciosus rhizome extract. Inter J Pharma Phyto Res

;7:383‑9.

Gil MI, Tomás‑Barberán FA, Hess‑Pierce B, Holcroft DM,

Kader AA. Antioxidant activity of pomegranate juice and its

relationship with phenolic composition and processing. J Agric

Food Chem 2000;48:4581‑9.

Bowler RP, Crapo JD. Oxidative stress in airways: Is there a role

for extracellular superoxide dismutase? Am J Respirat Crit Care

Med 2002;166(supplement_1):S38‑43.

Fukai T, Ushio‑Fukai M. Superoxide dismutases: Role in redox

signaling, vascular function, and diseases. Antioxid Redox Signal

;15:1583‑606.

Gul M, Demircan B, Taysi S, Oztasan N, Gumustekin K,

Siktar E, et al. Effects of endurance training and acute exhaustive

exercise on antioxidant defense mechanisms in rat heart. Comp

Biochem Physiol A Mol Integr Physiol 2006;143:239‑45.

Booth FW, Baldwin KM. Muscle plasticity: Energy demand and

supply processes. Compr Physiol 2010;1075‑123.

Kavazis AN, Alvarez S, Talbert E, Lee Y, Powers SK. Exercise

training induces a cardioprotective phenotype and alterations

in cardiac subsarcolemmal and intermyofibrillar mitochondrial

proteins. Am J Physiol HeartCirc Physiol 2009;297:H144‑52.

Dascombe BJ, Karunaratna M, Cartoon J, Fergie B, Goodman C.

Nutritional supplementation habits and perceptions of elite

athletes within a state‑based sporting institute. J Sci Med Sport

;13:274‑80.

Smith JC, Figeys D. Proteomics technology in systems biology.

Mol Biosyst 2006;2:364‑70.

Goldspink DF. Exercise‑related changes in protein turnover in

mammalian striated muscle. J Exp Biol 1991;160:127‑48.

Mishra NC. Introduction to Proteomics: Principles and

Applications. John Wiley and Sons; 2010.

Atkins JH, Johansson JS. Technologies to shape the future:

Proteomics applications in anesthesiology and critical care

medicine. Anesth Analg 2006;102:1207‑16.

Hirsch J, Hansen KC, Burlingame AL, Matthay MA. Proteomics:

Current techniques and potential applications to lung disease.

Am J Physiol Lung Cell Mol Physiol 2004;287:L1‑23.

Burniston JG. Changes in the rat skeletal muscle proteome

induced by moderate‑intensity endurance exercise. Biochim

Biophys Acta 2008;1784:1077‑86.

Bouchard C, Hoffman EP, editors. Genetic and Molecular

Aspects of Sports Performance. Wiley‑Blackwell; 2011.

Chong PK, Gan CS, Pham TK, Wright PC. Isobaric tags for

relative and absolute quantitation (iTRAQ) reproducibility:

Implication of multiple injections. J Proteome Res

;5:1232‑40.

Pingitore A, Lima GP, Mastorci F, Quinones A, Iervasi G,

Vassalle C. Exercise and oxidative stress: Potential effects of antioxidant dietary strategies in sports. Nutrition 2015;31:916‑22.

Powers SK, Criswell DA, Lawler JO, Martin DA, Lieu FK,

Ji LL, et al. Rigorous exercise training increases superoxide

dismutase activity in ventricular myocardium. Am J Physiol

;265:H2094‑8.

Judge S, Jang YM, Smith A, Selman C, Phillips T, Speakman JR,

et al. Exercise by lifelong voluntary wheel running reduces

subsarcolemmal and interfibrillar mitochondrial hydrogen

peroxide production in the heart. Am J Physiol Regul Integr

Comp Physiol 2005;289:R1564‑72.

Kılıç M, Ulusoy Ö, Cırrık S, Hindistan I, Özkaya Y. Effect

of exercise intensity on cerebrospinal fluid interleukin‑6

concentration during recovery from exhaustive exercise in rats.

Acta Physiol Hung 2013;101:21‑31.

Bernardes D, Oliveira‑Lima OC, da Silva TV, Faraco CC,

Leite HR, Juliano MA, et al. Differential brain and spinal

cord cytokine and BDNF levels in experimental autoimmune

encephalomyelitis are modulated by prior and regular exercise.

J Neuroimmunol 2013;264:24‑34.

Gobatto CA, De Mello MA, Sibuya CY, De Azevedo JR,

Dos Santos LA, Kokubun E. Maximal lactate steady state in rats

submitted to swimming exercise. Comp Biochem Physiol A Mol

Integr Physiol 2001;130:21‑7.

Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S,

Simonovic M, et al. The STRING database in 2017:

Quality‑controlled protein–protein association networks, made

broadly accessible. Nucleic Acids Res 2017;45:D362‑8.

Saito R, Smoot ME, Ono K, Ruscheinski J, Wang PL, Lotia S,

Pico AR, et al. A travel guide to Cytoscape plugins. Nature

Methods 2012;9:1069.

Bindea G, Galon J, Mlecnik B. CluePedia Cytoscape plugin:

Pathway insights using integrated experimental and in silico

data. Bioinformatics 2013;29:661‑3.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M,

Kirilovsky A, et al. ClueGO: A Cytoscape plug‑in to decipher

functionally grouped gene ontology and pathway annotation

networks. Bioinformatics 2009;25:1091‑3.

Fukai T, Folz RJ, Landmesser U, Harrison DG. Extracellular

superoxide dismutase and cardiovascular disease. Cardiovasc Res

;55:239‑49.

de Andrade LH, de Moraes WM, Junior EH, de Moura ED,

Antunes HK, Montemor J, et al. Aerobic exercise training

improves oxidative stress and ubiquitin proteasome system

activity in heart of spontaneously hypertensive rats. Mol Cell

Biochem 2015;402:193‑202.

Cunningham P, Geary M, Harper R, Pendleton A, Stover S. High

intensity sprint training reduces lipid peroxidation in fast‑twitch

skeletal muscle. J Exerc Physiol Online 2005;818‑25.

Franke A, McGovern DP, Barrett JC, Wang K, Radford‑Smith GL,

Ahmad T, et al. Genome‑wide meta‑analysis increases to 71 the

number of confirmed Crohn’s disease susceptibility loci. Nature

Genetics 2010;42:1118.

Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O.

Oxidative stress and antioxidant defense. World Allergy Organ J

;5:9‑19.

Kar S, Kavdia M. Modeling of biopterin‑dependent pathways

of eNOS for nitric oxide and superoxide production. Free Radic

Biol Med 2011;51:1411‑27.

Mccord JM. Human disease, free radicals, and the

oxidant/antioxidant balance. Clin Biochem 1993;26:351‑7.

Kajihara JI, Enomoto M, Nishijima K, Yabuuchi M, Katoh K.

Comparison of properties between human recombinant and

placental copper‑zinc SOD. J Biochem 1988;104:851‑4.

Moi P, Chan K, Asunis I, Cao A, Kan YW. Isolation of

NF‑E2‑related factor 2 (Nrf2), a NF‑E2‑like basic leucine zipper

transcriptional activator that binds to the tandem NF‑E2/AP1

repeat of the beta‑globin locus control region. Proc Natl Acad

Sci 1994;91:9926‑30.

Campuzano V, Montermini L, Lutz Y, Cova L, Hindelang C,

Jiralerspong S, et al. Frataxin is reduced in Friedreich ataxia

patients and is associated with mitochondrial membranes. Hum

Mol Genet 1997;6:1771‑80.

Cummings R, Parinandi N, Wang L, Usatyuk P, Natarajan V.

Phospholipase D/phosphatidic acid signal transduction: Role

and physiological significance in lung. Mol Cell Biochem

;234:99‑109.

Malavez Y, Gonzalez‑Mejia ME, Doseff AI. PRKCD (protein

kinase C, delta). Atlas of Genetics and Cytogenetics in Oncology

and Haematology. 2009.

Delpire E, Gagnon KB. SPAK and OSR1: STE20 kinases

involved in the regulation of ion homoeostasis and volume

control in mammalian cells. Biochem J 2008;409:321‑31.

Da Wei Huang BT, Stephens R, Baseler MW, Lane HC,

Lempicki RA. DAVID gene ID conversion tool. Bioinformation

:428‑30.

Zirah S, Kozin SA, Mazur AK, Blond A, Cheminant M,

Ségalas‑Milazzo I, et al. Structural changes of region 1‑16 of

the Alzheimer disease amyloid β‑peptide upon zinc binding and

in vitro aging. J Biol Chem 2006;281:2151‑61.

Cirrito JR, Yamada KA, Finn MB, Sloviter RS, Bales KR,

May PC, et al. Synaptic activity regulates interstitial fluid

amyloid‑β levels in vivo. Neuron 2005;48:913‑22.

Drakesmith H, Nemeth E, Ganz T. Ironing out ferroportin. Cell

Metab 2015;22:777‑87.

Jaiswal AK. Nrf2 signaling in coordinated activation of antioxidant

gene expression. Free Radic Biol Med 2004;36:1199‑207.

Yamaguchi T, Miki Y, Yoshida K. Protein kinase C δ activates

IκB‑kinase α to induce the p53 tumor suppressor in response to

oxidative stress. Cell Signal 2007;19:2088‑97.

Gaetke LM, Chow CK. Copper toxicity, oxidative stress, and

antioxidant nutrients. Toxicology 2003;189:147‑63.

Aslani BA, Ghobadi S. Studies on oxidants and antioxidants

with a brief glance at their relevance to the immune system. Life

Sci 2016;146:163‑73.

Forman HJ, Maiorino M, Ursini F. Signaling functions of

reactive oxygen species. Biochem 2010;49:835‑42.

Nisticò R, Piccirilli S, Cucchiaroni ML, Armogida M, Guatteo E,

Giampa C, et al. Neuroprotective effect of hydrogen peroxide

on an in vitro model of brain ischaemia. Br J Pharmacol

;153:1022‑9.

Schmucker S, Argentini M, Carelle‑Calmels N, Martelli A,

Puccio H. The in vivo mitochondrial two‑step maturation of

human frataxin. Hum Mol Genet 2008;17:3521‑31.

Cavadini P, O’Neill HA, Benada O, Isaya G. Assembly and

iron‑binding properties of human frataxin, the protein deficient in

Friedreich ataxia. Hum Mol Genet 2002;11:217‑27.

Krishnamurthy P, Wadhwani A. Antioxidant Enzymes and

Human Health. Antioxidant Enzyme 2012;1-7.

Tiwari BK, Pandey KB, Abidi AB, Rizvi SI. Markers of

oxidative stress during diabetes mellitus. J Biomark 2013;2013:8.

Rains JL, Jain SK. Oxidative stress, insulin signaling, and

diabetes. Free Radic Biol Med 2011;50:567‑75.

Simioni C, Zauli G, Martelli AM, Vitale M, Sacchetti G,

Gonelli A, et al. Oxidative stress: Role of physical exercise and

antioxidant nutraceuticals in adulthood and aging. Oncotarget

;9:17181.

Powers S, Sollanek K, Wiggs M, Demirel H, Smuder AJ.

Exercise‑induced improvements in myocardial antioxidant

capacity: The antioxidant players and cardioprotection. Free

Radic Res 2014;48:43‑51.

Adachi T, Ohta H, Yamada H, Futenma A, Kato K, Hirano K.

Quantitative analysis of extracellular‑superoxide dismutase in

serum and urine by ELISA with monoclonal antibody. Clin Chim

Acta 1992;212:89‑102.