Summary
This study investigated the tight junction (TJ) protein expression of the intestinal mucosa in a rat tail-suspension model under simulated weightlessness. Twenty-four Wistar rats were randomly divided into three groups: CON group (n=8), control; SUS-14 d group (n=8), tail-suspension for 14 days; SUS-21 d group (n=8), tail-suspension for 21 days. Occludin and Zonula Occluden-1 (ZO-1) expression levels were determined by immunohistochemical analysis and mRNA fluorescent quantitative PCR. Plasma levels of diamine oxidase (DAO) and d-lactate were determined using enzymatic spectrophotometry. Immunohistochemical results for occludin and ZO-1 showed disruption of the TJs in the intestinal mucosa in SUS-14 d and SUS-21 d groups. The expression levels of occludin and ZO-1 in SUS-21 d group were lower than those in SUS-14 d group, and significantly lower than those in CON group (Occldin: 0.86±0.02 vs 1.01±0.03 vs 1.63±0.03 and ZO-1: 0.82±0.01 vs 1.00±0.02 vs 1.55±0.01, P<0.01). Moreover, the levels of plasma DAO and d-lactate in SUS-21 d group were higher than those in SUS-14 d group, and significantly higher than those in CON group (DAO: 27.58±0.49 vs 20.74±0.49 vs 12.94±0.21 and d-lactate: 37.86±0.74 vs 28.26±1.01 vs 17.76±0.91, P<0.01). There were significant negative correlations between occludin or ZO-1 expression levels and DAO (r 2=0.9014, r 2=0.9355, P<0.01) or d-lactate levels (r 2=0.8989, r 2=0.9331, P<0.01). Occludin and Zo-1 were reduced in intestinal mucosa both in mRNA and protein levels in the rat tail-suspension model. The significant negative correlations between expression levels of TJs and plasma levels of DAO or d-lactate support the hypothesis that intestinal permeability is increased due to a decrease in TJ protein expression during tail-suspension from 14 days to 21 days.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Williams D, Kuipers A, Mukai C, et al. Acclimation during space flight: effects on human physiology. CMAJ, 2009,180(13):1317–1323
Rabot S, Szylit O, Nugon-Baudon L, et al. Variations in digestive physiology of rats after short duration flights aboard the US space shuttle. Dig Dis Sci, 2000,45(9): 1687–1695
Deitch EA. The role of intestinal barrier failure and bacterial translocation in the development of systemic infection and multiple organ failure. Arch Surg, 1990,125(3):403–404
Fanning AS, Mitic LL, Anderson JM. Transmembrane proteins in the tight junction barrier. J Am Soc Nephrol, 1999,10(6):1337–1345
Wittchen ES, Haskins J, Stevenson BR. Protein interactions at the tight junction. Actin has multiple binding partners, and ZO-1 forms independent complexes with ZO-2 and ZO-3. J Biol Chem, 1999,274(49):35 179–35 185
Vroling AB, Fokkens WJ, van Drunen CM. How epithelial cells detect danger: aiding the immune response. Allergy, 2008,63(9):1110–1123
Bounous G, Echavé V, Vobecky SJ, et al. Acute necrosis of the intestinal mucosa with high serum levels of diamine oxidase. Dig Dis Sci, 1984,29(9):872–874
Morey-Holton ER, Globus RK. Hindlimb unloading rodent model: technical aspects. J Appl Physiol, 2002,92(4):1367–1377
Fürst W, Schiesser A. Test for stereospecifity of an automated Dd-lactate assay based on selective removal of Ll-lactate. Anal Biochem, 1999,269(1):214–215
Takagi K, Nakao M, Ogura Y, et al. Sensitive colorimetric assay of serum diamine oxidase. Clin Chim Acta, 1994,226(1):67–75
Morey-Holton E, Globus RK, Kaplansky A, et al. The hindlimb unloading rat model: literature overview, technique update and comparison with space flight data. Adv Space Biol Med, 2005,10:7–40
Morey ER, Sabelman EE, Turner RT, et al. A new rat model simulating some aspects of space flight. Physiologist, 1979,22(6):S23–24
Zhang LF, Yu ZB, Ma J. Functional alterations in cardiac muscle after medium- or long-term simulated weightlessness and related cellular mechanisms. J Gravit Physiol, 1995,2(1):5–8
Schneeberger EE, Lynch RD. The tight junction: a multifunctional complex. Am J Physiol Cell Physiol, 2004, 286(6):C1213–1228
Nusrat A, Parkos CA, Verkade P, et al. Tight junctions are membrane microdomains. J Cell Sci, 2000,113(Pt 10):1771–1781
Aletti F, Baselli G. Model study of the effects of interactions between systemic and peripheral circulation on interstitial fluid balance. J Gravit Physiol, 2007,14(1):51–52
Gandia P, Saivin S, Lavit M, et al. Influence of simulated weightlessness on the pharmacokinetics of acetaminophen administered by the oral route: a study in the rat. Fundam Clin Pharmacol, 2004,18(1):57–64
Rivera CA, Tcharmtchi MH, Mendoza L, et al. Endotoxemia and hepatic injury in a rodent model of hindlimb unloading. J Appl Physiol, 2003,95(4): 1656–1663
Mankertz J, Tavalali S, Schmitz H, et al. Expression from the human occludin promoter is affected by tumor necrosis factor alpha and interferon gamma. J Cell Sci, 2000,113(Pt 11):2085–2090
Ye D, Ma I, Ma TY. Molecular mechanism of tumor necrosis factor-alpha modulation of intestinal epithelial tight junction barrier. Am J Physiol Gastrointest Liver Physiol, 2006,290(3):496–504
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Ying, C., Chunmin, Y., Qingsen, L. et al. Effects of simulated weightlessness on tight junction protein occludin and Zonula Occluden-1 expression levels in the intestinal mucosa of rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 31, 26–32 (2011). https://doi.org/10.1007/s11596-011-0145-5
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11596-011-0145-5