Ethanol disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated Rho/ROCK activation - PubMed (original) (raw)
. 2014 Apr 15;306(8):G677-85.
doi: 10.1152/ajpgi.00236.2013. Epub 2014 Feb 20.
Affiliations
- PMID: 24557761
- DOI: 10.1152/ajpgi.00236.2013
Free article
Ethanol disrupts intestinal epithelial tight junction integrity through intracellular calcium-mediated Rho/ROCK activation
Elhaseen Elamin et al. Am J Physiol Gastrointest Liver Physiol. 2014.
Free article
Abstract
Evidence indicates that ethanol-induced intestinal barrier dysfunction and subsequent endotoxemia plays a key role in the pathogenesis of alcoholic liver disease. Recently, it has been demonstrated that ethanol induces RhoA kinase activation in intestinal epithelium, thereby disrupting barrier integrity. In this study, the role of a rise in intracellular calcium concentration ([Ca(2+)]i) in ethanol-induced Rho-associated coiled coil-forming kinase (Rho/ROCK) activation and barrier disruption was investigated in Caco-2 cell monolayers. Treatment of Caco-2 monolayers with 40 mmol/l ethanol induced [Ca(2+)]i release as indicated by increased relative fluorescent units of Fluo-3 from 0.06 ± 0.02 to 2.27 ± 1.96 (P < 0.0001). Pretreatment with 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) completely inhibited the release, whereas the inositol 1,4,5-triphosphate receptor (IP3R)-antagonist, Xestospongin C, partially inhibited the ethanol-induced [Ca(2+)]i release (from 2.27 ± 1.96 to 0.03 ± 0.01; P < 0.0001 and from 2.27 ± 1.96 to 1.19 ± 1.80; P < 0.001, respectively). The rise in [Ca(2+)]i was paralleled with increased intestinal permeability, which could be attenuated by either BAPTA-AM or Xestospongin C. Furthermore, ethanol induced Rho/ROCK activation, as indicated by increased phosphorylation of myosin-binding subunit, which could be prevented either by BAPTA, Xestospongin C, or the specific Rho/ROCK inhibitor Y27632. Finally, inhibition of Rho/ROCK kinase by Y27632 ameliorated the ethanol-induced redistribution of zonula occluden-1, adherens junction proteins including E-cadherin and β-catenin, and also disorganization of F-actin. These findings suggest that ethanol-induced [Ca(2+)]i release, mediated by stimulating IP3R-gated Ca(2+) channel, activates Rho/ROCK in Caco-2 cells, thereby contributing to ethanol-induced intestinal barrier dysfunction.
Keywords: Caco-2; Rho kinase; ethanol; inositol 1,4,5-triphosphate receptor; intestinal epithelial barrier; intracellular calcium; tight junction.
Similar articles
- Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium.
Samak G, Chaudhry KK, Gangwar R, Narayanan D, Jaggar JH, Rao R. Samak G, et al. Biochem J. 2015 Feb 1;465(3):503-15. doi: 10.1042/BJ20140450. Biochem J. 2015. PMID: 25377781 Free PMC article. - CaV1.3 channels and intracellular calcium mediate osmotic stress-induced N-terminal c-Jun kinase activation and disruption of tight junctions in Caco-2 CELL MONOLAYERS.
Samak G, Narayanan D, Jaggar JH, Rao R. Samak G, et al. J Biol Chem. 2011 Aug 26;286(34):30232-43. doi: 10.1074/jbc.M111.240358. Epub 2011 Jul 7. J Biol Chem. 2011. PMID: 21737448 Free PMC article. - The Regulation of Intestinal Mucosal Barrier by Myosin Light Chain Kinase/Rho Kinases.
Jin Y, Blikslager AT. Jin Y, et al. Int J Mol Sci. 2020 May 18;21(10):3550. doi: 10.3390/ijms21103550. Int J Mol Sci. 2020. PMID: 32443411 Free PMC article. Review. - Endotoxemia and gut barrier dysfunction in alcoholic liver disease.
Rao R. Rao R. Hepatology. 2009 Aug;50(2):638-44. doi: 10.1002/hep.23009. Hepatology. 2009. PMID: 19575462 Free PMC article. Review. No abstract available.
Cited by
- IL-22-Activated MUC13 Impacts on Colonic Barrier Function through JAK1/STAT3, SNAI1/ZEB1 and ROCK2/MAPK Signaling.
Breugelmans T, Arras W, Oosterlinck B, Jauregui-Amezaga A, Somers M, Cuypers B, Laukens K, De Man JG, De Schepper HU, De Winter BY, Smet A. Breugelmans T, et al. Cells. 2023 Apr 23;12(9):1224. doi: 10.3390/cells12091224. Cells. 2023. PMID: 37174625 Free PMC article. - Role of Intestinal Microbes in Chronic Liver Diseases.
Xu M, Luo K, Li J, Li Y, Zhang Y, Yuan Z, Xu Q, Wu X. Xu M, et al. Int J Mol Sci. 2022 Oct 21;23(20):12661. doi: 10.3390/ijms232012661. Int J Mol Sci. 2022. PMID: 36293518 Free PMC article. Review. - Propolis Ameliorates Alcohol-Induced Depressive Symptoms in C57BL/6J Mice by Regulating Intestinal Mucosal Barrier Function and Inflammatory Reaction.
Wang P, Guo P, Wang Y, Teng X, Zhang H, Sun L, Xue M, Liang H. Wang P, et al. Nutrients. 2022 Mar 12;14(6):1213. doi: 10.3390/nu14061213. Nutrients. 2022. PMID: 35334870 Free PMC article. - Soluble Immune Checkpoints Are Dysregulated in COVID-19 and Heavy Alcohol Users With HIV Infection.
Li W, Syed F, Yu R, Yang J, Xia Y, Relich RF, Russell PM, Zhang S, Khalili M, Huang L, Kacena MA, Zheng X, Yu Q. Li W, et al. Front Immunol. 2022 Feb 23;13:833310. doi: 10.3389/fimmu.2022.833310. eCollection 2022. Front Immunol. 2022. PMID: 35281051 Free PMC article. Review. - Mechanosensitive calcium flashes promote sustained RhoA activation during tight junction remodeling.
Varadarajan S, Chumki SA, Stephenson RE, Misterovich ER, Wu JL, Dudley CE, Erofeev IS, Goryachev AB, Miller AL. Varadarajan S, et al. J Cell Biol. 2022 Apr 4;221(4):e202105107. doi: 10.1083/jcb.202105107. Epub 2022 Mar 7. J Cell Biol. 2022. PMID: 35254388 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous