Influence of endurance exercise training on antioxidant enzymes, tight junction proteins, and inflammatory markers in the rat ileum

A Maleah Holland, Hayden W Hyatt, Ashley J Smuder, Kurt J Sollanek, Aaron B Morton, Michael D Roberts, Andreas N Kavazis, A Maleah Holland, Hayden W Hyatt, Ashley J Smuder, Kurt J Sollanek, Aaron B Morton, Michael D Roberts, Andreas N Kavazis

Abstract

Background: This study investigated the effects of endurance exercise training on ileum antioxidant status, as well as tight junction, inflammatory, and nutrient transporter gene expression.

Methods: Sprague-Dawley rats (4 month old) were assigned to sedentary (SED) or endurance exercise-training (EXE) groups (n = 8/group). EXE animals were trained on the treadmill for 10 days at a speed of 30 m/min at 0° incline for 60 min/day. SED and EXE animals were sacrificed (24 h after the final training bout) and the ileum was stored for analyses.

Results: The ileum of EXE had higher (p < 0.05) antioxidant protein levels of manganese superoxide dismutase and catalase compared to SED with no change (p > 0.05) in the lipid peroxidation biomarker 4-hydroxynonenal. Ileum mRNA expression of the tight junction gene zonulin increased (p < 0.05) and claudin 1 decreased (p < 0.05) in EXE compared to SED, but occludin and zonula occluden 1 were not different (p > 0.05) between SED and EXE. The ileum mRNA expressions of seven nutrient transporters (SLC5A8, SLC7A6, SLC6A19, SLC7A7, SLC27A2, SLC16A10, and SLC15A1) were not different between the two groups (p > 0.05). EXE had lower ileum TNFα mRNA expression (p < 0.05) compared to SED. No changes (p > 0.05) were found in the other inflammatory mRNAs including NFκB, IFNγ, IL6, CCL2, TLR4, and IL10. In addition, no changes in p-p65:p65 were detected.

Conclusions: These findings suggest that 10 days of endurance exercise training up-regulates key endogenous antioxidant enzymes, decreases select inflammation markers, and alters select markers of tight junction permeability.

Figures

Fig. 1
Fig. 1
Ileum oxidative stress. a Manganese superoxide dismutase (SOD2), and b catalase protein levels in ileum tissue of sedentary and exercised animals. c Lipid peroxidation was compared by using 4-hydroxynonenal (4-HNE). Representative Western blots are shown to the right of the graphs (n = 8 per group). *p < 0.05
Fig. 2
Fig. 2
Expression of tight junction genes in the ileum. a Occludin (OCLN), b claudin-1 (CLDN1), c zona occludens-1 (ZO1), and d haptogloblin/zonulin (zonulin). *p < 0.05
Fig. 3
Fig. 3
Ileum inflammatory markers. Gene expression of pro-inflammatory a nuclear factor kappa-B (NFKB), b tumor necrosis factor-α (TNFα), c interferon-γ (IFNγ), d interleukin 6 (IL6), e chemokine (C–C motif) ligand 2 (CCL2), and f toll-like receptor 4 (TLR4). Gene expression of anti-inflammatory g IL10 in the ileum. h protein levels of p-p65:p65. *p < 0.05
Fig. 4
Fig. 4
Gene expression of nutrient transporters in the ileum. a Oligopeptide transporter: PEPT1 (SLC15A1), b neutral amino acid transporter (SLC6A19), c amino acid transporter light chain, Y + L System (SLC7A6), d amino acid transporter light chain, Y + L System (SLC7A7), e aromatic amino acid transporter (SLC16A10), f lipid transporters: sodium/monocarboxylate cotransporter (SLC5A8), g fatty acid transporter (SLC27A2), and h neurotransmitter serotonin transporter (SLC6A4)

References

    1. Brouns F, Beckers E. Is the gut an athletic organ? Digestion, absorption and exercise. Sports Med. 1993;15(4):242–257. doi: 10.2165/00007256-199315040-00003.
    1. Gloire G, Legrand-Poels S, Piette J. NF-kappaB activation by reactive oxygen species: fifteen years later. Biochem Pharmacol. 2006;72(11):1493–1505. doi: 10.1016/j.bcp.2006.04.011.
    1. Rowell LB, Blackmon JR, Bruce RA. Indocyanine green clearance and estimated hepatic blood flow during mild to maximal exercise in upright man. J Clin Invest. 1964;43:1677–1690. doi: 10.1172/JCI105043.
    1. Pals KL, Chang RT, Ryan AJ, Gisolfi CV. Effect of running intensity on intestinal permeability. J Appl Physiol (1985) 1997;82(2):571–576.
    1. Peters HP, De Vries WR, Vanberge-Henegouwen GP, Akkermans LM. Potential benefits and hazards of physical activity and exercise on the gastrointestinal tract. Gut. 2001;48(3):435–439. doi: 10.1136/gut.48.3.435.
    1. Hall DM, Buettner GR, Oberley LW, Xu L, Matthes RD, Gisolfi CV. Mechanisms of circulatory and intestinal barrier dysfunction during whole body hyperthermia. Am J Physiol Heart Circ Physiol. 2001;280(2):H509–H521.
    1. Rosa EF, Freymuller E, Ihara SS, Aboulafia J, Nouailhetas VL. Damaging effects of intense repetitive treadmill running on murine intestinal musculature. J Appl Physiol (1985) 2008;104(5):1410–1417. doi: 10.1152/japplphysiol.00377.2007.
    1. Lambert GP. Role of gastrointestinal permeability in exertional heatstroke. Exerc Sport Sci Rev. 2004;32(4):185–190. doi: 10.1097/00003677-200410000-00011.
    1. Criswell D, Powers S, Dodd S, Lawler J, Edwards W, Renshler K, Grinton S. High intensity training-induced changes in skeletal muscle antioxidant enzyme activity. Med Sci Sports Exerc. 1993;25(10):1135–1140. doi: 10.1249/00005768-199310000-00009.
    1. Sasaki M, Joh T. Oxidative stress and ischemia-reperfusion injury in gastrointestinal tract and antioxidant, protective agents. J Clin Biochem Nutr. 2007;40(1):1–12. doi: 10.3164/jcbn.40.1.
    1. van Wijck K, Lenaerts K, van Loon LJ, Peters WH, Buurman WA, Dejong CH. Exercise-induced splanchnic hypoperfusion results in gut dysfunction in healthy men. PLoS One. 2011;6(7):e22366. doi: 10.1371/journal.pone.0022366.
    1. Hoffman-Goetz L, Pervaiz N, Guan J. Voluntary exercise training in mice increases the expression of antioxidant enzymes and decreases the expression of TNF-alpha in intestinal lymphocytes. Brain Behav Immun. 2009;23(4):498–506. doi: 10.1016/j.bbi.2009.01.015.
    1. de Lira CA, Vancini RL, Ihara SS, da Silva AC, Aboulafia J, Nouailhetas VL. Aerobic exercise affects C57BL/6 murine intestinal contractile function. Eur J Appl Physiol. 2008;103(2):215–223. doi: 10.1007/s00421-008-0689-7.
    1. Rosa EF, Silva AC, Ihara SS, Mora OA, Aboulafia J, Nouailhetas VL. Habitual exercise program protects murine intestinal, skeletal, and cardiac muscles against aging. J Appl Physiol (1985) 2005;99(4):1569–1575. doi: 10.1152/japplphysiol.00417.2005.
    1. Haglund U. Gut ischaemia. Gut. 1994;35(1 Suppl):S73–S76. doi: 10.1136/gut.35.1_Suppl.S73.
    1. Clausen JP. Effect of physical training on cardiovascular adjustments to exercise in man. Physiol Rev. 1977;57(4):779–815.
    1. Furuse M, Hata M, Furuse K, Yoshida Y, Haratake A, Sugitani Y, Noda T, Kubo A, Tsukita S. Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol. 2002;156(6):1099–1111. doi: 10.1083/jcb.200110122.
    1. Podolsky DK. Mucosal immunity and inflammation. V. Innate mechanisms of mucosal defense and repair: the best offense is a good defense. Am J Physiol. 1999;277(3 Pt 1):G495–G499.
    1. Fasano A. Regulation of intercellular tight junctions by zonula occludens toxin and its eukaryotic analogue zonulin. Ann N Y Acad Sci. 2000;915:214–222. doi: 10.1111/j.1749-6632.2000.tb05244.x.
    1. Fasano A. Physiological, pathological, and therapeutic implications of zonulin-mediated intestinal barrier modulation: living life on the edge of the wall. Am J Pathol. 2008;173(5):1243–1252. doi: 10.2353/ajpath.2008.080192.
    1. Teerapornpuntakit J, Dorkkam N, Wongdee K, Krishnamra N, Charoenphandhu N. Endurance swimming stimulates transepithelial calcium transport and alters the expression of genes related to calcium absorption in the intestine of rats. Am J Physiol Endocrinol Metab. 2009;296(4):E775–E786. doi: 10.1152/ajpendo.90904.2008.
    1. Dokladny K, Moseley PL, Ma TY. Physiologically relevant increase in temperature causes an increase in intestinal epithelial tight junction permeability. Am J Physiol Gastrointest Liver Physiol. 2006;290(2):G204–G212. doi: 10.1152/ajpgi.00401.2005.
    1. Lambert GP, Gisolfi CV, Berg DJ, Moseley PL, Oberley LW, Kregel KC. Selected contribution: Hyperthermia-induced intestinal permeability and the role of oxidative and nitrosative stress. J Appl Physiol (1985) 2002;92(4):1750–1761. doi: 10.1152/japplphysiol.00787.2001.
    1. Sapone A, de Magistris L, Pietzak M, Clemente MG, Tripathi A, Cucca F, Lampis R, Kryszak D, Carteni M, Generoso M, et al. Zonulin upregulation is associated with increased gut permeability in subjects with type 1 diabetes and their relatives. Diabetes. 2006;55(5):1443–1449. doi: 10.2337/db05-1593.
    1. Ma TY, Iwamoto GK, Hoa NT, Akotia V, Pedram A, Boivin MA, Said HM. TNF-alpha-induced increase in intestinal epithelial tight junction permeability requires NF-kappa B activation. Am J Physiol Gastrointest Liver Physiol. 2004;286(3):G367–G376. doi: 10.1152/ajpgi.00173.2003.
    1. Petersen AM, Pedersen BK. The anti-inflammatory effect of exercise. J Appl Physiol (1985) 2005;98(4):1154–1162. doi: 10.1152/japplphysiol.00164.2004.
    1. Ferraris RP, Carey HV. Intestinal transport during fasting and malnutrition. Annu Rev Nutr. 2000;20:195–219. doi: 10.1146/annurev.nutr.20.1.195.
    1. Lee CY. Chronic restraint stress induces intestinal inflammation and alters the expression of hexose and lipid transporters. Clin Exp Pharmacol Physiol. 2013;40(6):385–391. doi: 10.1111/1440-1681.12096.
    1. Lee CY. Adenosine protects Sprague Dawley rats from high-fat diet and repeated acute restraint stress-induced intestinal inflammation and altered expression of nutrient transporters. J Anim Physiol Anim Nutr (Berl) 2015;99(2):317–325. doi: 10.1111/jpn.12247.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi