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Targeting mitochond...
Targeting mitochondria-derived reactive oxygen species to reduce epithelial barrier dysfunction and colitis
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- Wang, Arthur (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Keita, Åsa V. (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Kirurgiska kliniken US
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- Phan, Van (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- McKay, Catherine M. (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Schoultz, Ida, 1979- (author)
- Örebro universitet,Institutionen för hälsovetenskap och medicin,Nutrition-Gut-Brain Interactions Research Centre, the Faculty of Medicine, Örebro University, Örebro, Sweden
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- Lee, Joshua (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Murphy, Michael P. (author)
- MRC Mitochondrial Biol Unit, Cambridge, England,MRC-Mitochondrial Biology Unit, Cambridge, United Kingdom
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- Fernando, Maria (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Ronaghan, Natalie (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Balce, Dale (author)
- Joan Snyder Inst Chron Dis, Dept Comparat Biol & Expt Med, Fac Vet Med, Univ Calgary, Calgary AB, Canada,Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
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- Yates, Robin (author)
- Joan Snyder Inst Chron Dis, Dept Comparat Biol & Expt Med, Fac Vet Med, Univ Calgary, Calgary AB, Canada,Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary, Alberta, Canada
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- Dicay, Michael (author)
- Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Beck, Paul L. (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada; Department of Comparative Biology and Experimental Medicine, Faculty of Veterinary Medicine, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Department of Medicine, University of Calgary, Calgary, Alberta, Canada
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- MacNaughton, Wallace K. (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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- Söderholm, Johan D. (author)
- Östergötlands Läns Landsting,Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Kirurgiska kliniken US
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- Mckay, Derek M. (author)
- Department of Physiology and Pharmacology, 1877 Health Sciences Center, University of Calgary, Calgary AB, Canada,Gastrointestinal Research Group, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada, Inflammation Research Network, Department of Physiology and Pharmacology, Calvin, Phoebe, and Joan Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
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In: American Journal of Pathology. - : Elsevier BV. - 0002-9440 .- 1525-2191. ; 184:9, s. 2516-2527
- Related links:
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https://doi.org/10.1...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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Abstract
Subject headings
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- Epithelial permeability is often increased in inflammatory bowel diseases. We hypothesized that perturbed mitochondrial function would cause barrier dysfunction and hence epithelial mitochondria could be targeted to treat intestinal inflammation. Mitochondrial dysfunction was induced in human colon-derived epithelial cell lines or colonic biopsy specimens using dinitrophenol, and barrier function was assessed by transepithelial flux of Escherichia coil with or without mitochondria-targeted antioxidant (MTA) cotreatment. The impact of mitochondria-targeted antioxidants on gut permeability and dextran sodium sulfate (DSS)-induced colitis in mice was tested. Mitochondrial superoxide evoked by dinitrophenol elicited significant internalization and transtocation of E. coil across epithelia and control colonic biopsy specimens, which was more striking in Crohn's disease biopsy specimens; the mitochondria-targeted antioxidant, MitoTEMPO, inhibited these barrier defects. Increased gut permeability and reduced epithelial mitochondrial voltage-dependent anion channel expression were observed 3 days after DSS. These changes and the severity of DSS-colitis were reduced by MitoTEMPO treatment. In vitro DSS-stimulated IL-8 production by epithelia was reduced by MitoTEMPO. Metabolic stress evokes significant penetration of commensal bacteria across the epithelium, which is mediated by mitochondria-derived superoxide acting as a signaling, not a cytotoxic, molecule. MitoTEMPO inhibited this barrier dysfunction and suppressed colitis in DSS-colitis, likely via enhancing barrier function and inhibiting proinflammatory cytokine production. These novel findings support consideration of MTAs in the maintenance of epithelial barrier function and the management of inflammatory bowel diseases.
Subject headings
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Patologi
- Pathology
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Wang, Arthur
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Keita, Åsa V.
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Phan, Van
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McKay, Catherine ...
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Schoultz, Ida, 1 ...
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Lee, Joshua
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Murphy, Michael ...
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Fernando, Maria
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Ronaghan, Natali ...
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Balce, Dale
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Yates, Robin
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Dicay, Michael
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Beck, Paul L.
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MacNaughton, Wal ...
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Söderholm, Johan ...
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Mckay, Derek M.
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- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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American Journal ...
- By the university
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Örebro University
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Linköping University