Effects of eight weeks aerobic training on kynurenine and gene and protein expression of aryl hydrocarbon receptor in the heart of male rats

authors:

avatar Pouria Nori , avatar Rouhollah Haghshenas , *

Koomesh: Vol.24, issue 1; 162-167
published online: March 03, 2021
article type: issue_documents_importer
received: April 03, 2021
accepted: August 03, 2021

how to cite: Nori P, Haghshenas R. Effects of eight weeks aerobic training on kynurenine and gene and protein expression of aryl hydrocarbon receptor in the heart of male rats. koomesh. 2022;24(1):e154098. 

Abstract

Introduction: Understanding the molecular cellular mechanisms of the heart is essential for the prevention and treatment of cardiovascular disease. This study aimed was to investigate the effect of aerobic exercise on the kynurenine and gene and protein expression of aryl hydrocarbon receptor (AHR) in the heart tissue of healthy male Wistar rats. Materials and Methods: The present study is an experimental study design that twelve male Wistar rats were prepared and after adaptation to the environment were divided into 2 groups: control and training. Then, rats in the exercise group performed running on the treadmill for eight weeks, 5 sessions per week, speed between 10 and 26 meters per minute increasingly. After tissue resection and RNA extraction and cDNA preparation, the Real-Time PCR method was used to measure the gene expression of Ahr, and the ELIZA method was used to measure the expression of AHR protein and kynurenine. Results: The results showed that aerobic exercise led to a significant decrease in the protein expression of AHR (P=0.001) and metabolite of kynurenine (P=0.003), but no significant changes were observed in the level of Ahr gene expression. Conclusion: Considering the positive effect of aerobic exercise on heart function and the reduction of AHR and kynurenine by this type of exercise, it seems that reducing the activity level of this cell signaling pathway is suitable for improving heart function under normal conditions.

References

  • 1.

    Santos LP, Umpierre D. Exercise, cardiovascular health, and risk factors for atherosclerosis: a narrative review on these complex relationships and caveats of literature. Front Physiol 2020; 11: 840. https://doi.org/10.3389/fphys.2020.00840 PMid:32848823 PMCid:PMC7411151.

  • 2.

    Seyedrezazadeh E, Faramarzi E, Bakhtiyari N, Ansarin A, Gilani N, Amiri-Sadeghan A, et al. Association of NOS3-c.894G>T transversion with susceptibility to metabolic syndrome in Azar-cohort population: A case-control study and in silico analysis of the SNP molecular effects. Iran J Basic Med Sci 2021; 24: 408-419.

  • 3.

    Koutroumpi M, Pitsavos C, Stefanadis C. The role of exercise in cardiovascular rehabilitation: a review. Acta Cardiol 2008; 63: 73-79. https://doi.org/10.2143/AC.63.1.2025335 PMid:18372584.

  • 4.

    Bouaziz W, Vogel T, Schmitt E, Kaltenbach G, Geny B, Lang PO. Bnfices de l'activit physique en endurance chez les seniors gs de 70 ans ou plus: une revue systmatique [Health benefits of aerobic training programs in adults aged 70 or over: A systematic review]. Presse Med 2017; 46: 794-807. https://doi.org/10.1016/j.lpm.2017.05.028 PMid:28668364.

  • 5.

    Gilani N, Kazemnejad A, Zayeri F, Yazdani J. Comparison of marginal logistic model with repeated measures and conditional logistic model in risk factors affecting hypertension. J Mazandaran Univ Med Sci 2011; 21: 27-35. (Persian).

  • 6.

    Haghshenas R. The effect of rope training on the plasma level of angiopoietin-4, interleukin-6, and lipid profile of overweight boys. Iran J Endocrinol Metab 2020; 22: 162-168.

  • 7.

    Sobhani F, Haghshenas R, Rahimi M. Effect of eight weeks aerobic training and supplementation of green tea on apelin plasma levels and insulin resistance in elderly women with type 2 diabetes. J Mazandaran Univ Med Sci 2019; 28: 84-93. (Persian).

  • 8.

    Litviukov M, Talavera-Lpez C, Maatz H, Reichart D, Worth CL, Lindberg EL, et al. Cells of the adult human heart. Nature 2020; 588: 466-472. https://doi.org/10.1038/s41586-020-2797-4 PMid:32971526 PMCid:PMC7681775.

  • 9.

    Gilani N, Kazemnejad A, Zayeri F, Hadaegh F, Azizi F, Khalili D. Anthropometric indices as predictors of coronary heart disease risk: joint modeling of longitudinal measurements and time to event. Iran J Public Health 2017; 46: 1546-1554.

  • 10.

    Hassankhani H, Soheili A, Vahdati SS, Mozaffari FA, Fraser JF, Gilani N. Treatment delays for patients with acute ischemic stroke in an Iranian emergency department: a retrospective chart review. Ann Emerg Med 2019; 73: 118-129. https://doi.org/10.1016/j.annemergmed.2018.08.435 PMid:30318375.

  • 11.

    Carreira VS. The aryl hydrocarbon receptor contributions to cardiovascular development and health. 2015; (Doctoral dissertation, University of Cincinnati).

  • 12.

    Shankar P, Dasgupta S, Hahn ME, Tanguay RL. A review of the functional roles of the zebrafish aryl hydrocarbon receptors. Toxicol Sci 2020; 178: 215-238. https://doi.org/10.1093/toxsci/kfaa143 PMid:32976604 PMCid:PMC7706399.

  • 13.

    Volkova M, Palmeri M, Russell KS, Russell RR. Activation of the aryl hydrocarbon receptor by doxorubicin mediates cytoprotective effects in the heart. Cardiovasc Res 2011; 90: 305-314. https://doi.org/10.1093/cvr/cvr007 PMid:21233252 PMCid:PMC3078799.

  • 14.

    Pulignani S, Borghini A, Vecoli C, Foffa I, Ait-Ali L, Andreassi MG. A functional aryl hydrocarbon receptor genetic variant, alone and in combination with parental exposure, is a risk factor for congenital heart disease. Cardiovasc Toxicol 2018; 18: 261-267. https://doi.org/10.1007/s12012-017-9436-9 PMid:29185192.

  • 15.

    Kaiser H, Parker E, Hamrick MW. Kynurenine signaling through the aryl hydrocarbon receptor: Implications for aging and healthspan. Exp Gerontol 2020; 130: 110797. https://doi.org/10.1016/j.exger.2019.110797 PMid:31786316 PMCid:PMC7899131.

  • 16.

    Rojas IY, Moyer BJ, Ringelberg CS, Wilkins OM, Pooler DB, Ness DB, et al. Kynurenine-induced aryl hydrocarbon receptor signaling in mice causes body mass gain, liver steatosis, and hyperglycemia. Obesity (Silver Spring) 2021; 29: 337-349. https://doi.org/10.1002/oby.23065 PMid:33491319.

  • 17.

    Schlittler M, Goiny M, Agudelo LZ, Venckunas T, Brazaitis M, Skurvydas A, et al. Endurance exercise increases skeletal muscle kynurenine aminotransferases and plasma kynurenic acid in humans. Am J Physiol Cell Physiol 2016; 310: C836-840. https://doi.org/10.1152/ajpcell.00053.2016 PMid:27030575.

  • 18.

    Joisten N, Kummerhoff F, Koliamitra C, Schenk A, Walzik D, Hardt L, et al. Exercise and the kynurenine pathway: current state of knowledge and results from a randomized cross-over study comparing acute effects of endurance and resistance training. Exerc Immunol Rev 2020; 26: 24-42.

  • 19.

    Cervenka I, Agudelo LZ, Ruas JL. Kynurenines: Tryptophan's metabolites in exercise, inflammation, and mental health. Science 2017; 357: eaaf9794. https://doi.org/10.1126/science.aaf9794 PMid:28751584.

  • 20.

    Haghshenas R, Jafari M, Ravasi A, Kordi M, Gilani N, Shariatzadeh M, et al. The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma. Iran J Basic Med Sci 2014; 17: 237-243.

  • 21.

    Schenk A, Joisten N, Walzik D, Koliamitra C, Schoser D, Bloch W, et al. Acute exercise impacts AhR and PD-1 levels of CD8+ T-cells-Exploratory results from a randomized cross-over trial comparing endurance versus resistance exercise. Eur J Appl Physiol 2021; 121: 637-644. https://doi.org/10.1007/s00421-020-04552-w PMid:33211154 PMCid:PMC7862188.

  • 22.

    Koliamitra C, Javelle F, Joisten N, Shimabukuro-Vornhagen A, Bloch W, et al. Do acute exercise-induced activations of the kynurenine pathway induce regulatory T-cells on the long-term? - a theoretical frame work supported by pilot data. J Sports Sci Med 2019; 18: 669-673.

  • 23.

    Strasser B, Geiger D, Schauer M, Gatterer H, Burtscher M, Fuchs D. Effects of exhaustive aerobic exercise on tryptophan-kynurenine metabolism in trained athletes. PLoS One 2016; 11: e0153617. https://doi.org/10.1371/journal.pone.0153617 PMid:27124720 PMCid:PMC4849644.

  • 24.

    Zimmer P, Schmidt ME, Prentzell MT, Berdel B, Wiskemann J, Kellner KH, et al. Resistance exercise reduces kynurenine pathway metabolites in breast cancer patients undergoing radiotherapy. Front Oncol 2019; 9: 962. https://doi.org/10.3389/fonc.2019.00962 PMid:31612110 PMCid:PMC6773833.

  • 25.

    Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Mackey JR. Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol 2005; 98: 1534-1540. https://doi.org/10.1152/japplphysiol.00566.2004 PMid:15772062.

  • 26.

    Fakhari A, Gharepapagh E, Dabiri S, Gilani N. Correlation of cancer antigen 15-3 (CA15-3) serum level and bony metastases in breast cancer patients. Med J Islam Repub Iran 2019; 33: 142. https://doi.org/10.47176/mjiri.33.142 PMid:32280648 PMCid:PMC7137849.

  • 27.

    Pertovaara M, Raitala A, Lehtimki T, Karhunen PJ, Oja SS, Jylh M, et al. Indoleamine 2,3-dioxygenase activity in nonagenarians is markedly increased and predicts mortality. Mech Ageing Dev 2006; 127: 497-499. https://doi.org/10.1016/j.mad.2006.01.020 PMid:16513157.

  • 28.

    Kim BJ, Hamrick MW, Yoo HJ, Lee SH, Kim SJ, Koh JM, et al. The detrimental effects of kynurenine, a tryptophan metabolite, on human bone metabolism. J Clin Endocrinol Metab 2019; 104: 2334-2342. https://doi.org/10.1210/jc.2018-02481 PMid:30715395 PMCid:PMC6497841.

  • 29.

    Yu E, Ruiz-Canela M, Guasch-Ferr M, Zheng Y, Toledo E, Clish CB, et al. Increases in plasma tryptophan are inversely associated with incident cardiovascular disease in the prevencin con dieta mediterrnea (PREDIMED) study. J Nutr 2017; 147: 314-322. https://doi.org/10.3945/jn.116.241711 PMid:28179491 PMCid:PMC5320398.

  • 30.

    Lustgarten MS, Fielding RA. Metabolites related to renal function, immune activation, and carbamylation are associated with muscle composition in older adults. Exp Gerontol 2017; 100: 1-10. https://doi.org/10.1016/j.exger.2017.10.003 PMid:29030163 PMCid:PMC6556217.

  • 31.

    Ikuta T, Eguchi H, Tachibana T, Yoneda Y, Kawajiri K. Nuclear localization and export signals of the human aryl hydrocarbon receptor. J Biol Chem 1998; 30; 273: 2895-2904. https://doi.org/10.1074/jbc.273.5.2895 PMid:9446600.

  • 32.

    Pearson MJ, Smart NA. Effect of exercise training on endothelial function in heart failure patients: A systematic review meta-analysis. Int J Cardiol 2017; 231: 234-243. https://doi.org/10.1016/j.ijcard.2016.12.145 PMid:28089145.

  • 33.

    Gilani N, Haghshenas R, Esmaeili M. Application of multivariate longitudinal models in SIRT6, FBS, and BMI analysis of the elderly. Aging Male 2019; 22: 260-265. https://doi.org/10.1080/13685538.2018.1477933 PMid:29901417.

  • 34.

    Soori R, Mosayebi Z, Pournemati P, Akbarneghad A. Effect of high-intensity interval training on tissue changes of collagen type 1 and fibrosis percent in male rats with myocardial infarction. Koomesh 2021; 23: 267-274. (Persian). https://doi.org/10.52547/koomesh.23.2.267.

  • 35.

    Avazah A, Fetrat MK, Bashar FR. Effect of progressive muscle relaxation on the vital signs and oxygenation indexes in patients under coronary artery bypass graft surgery: A triple blinded randomized clinical trial. Koomesh 2019; 21: 423-436. (Persian).

  • 36.

    Gilani N, Esmaeili A, Haghshenas R. The effect of eight weeks concurrent training and supplementation of L_Arginine on plasma level of 8-hydroxydeoxyguanosine (8-OHdG), malondialdehyde and total antioxidant capacity in elderly men (Multivariate Longitudinal Modeling). Iran J Endocrinol Metab 2018; 20: 195-202.