Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease
Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a central step in celiac disease (CD) pathogenesis. Microbial transglutaminase (mTG) mimics the enzymatic function of TG2 and might play a role in CD. TG2 is inhibited by endogenous oxidative endoplasmic reticulum-reside...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/2248 |
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| author | Sebastian Stricker Silvia Rudloff Jan De Laffolie Klaus-Peter Zimmer |
| author_facet | Sebastian Stricker Silvia Rudloff Jan De Laffolie Klaus-Peter Zimmer |
| author_sort | Sebastian Stricker |
| collection | DOAJ |
| description | Enzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a central step in celiac disease (CD) pathogenesis. Microbial transglutaminase (mTG) mimics the enzymatic function of TG2 and might play a role in CD. TG2 is inhibited by endogenous oxidative endoplasmic reticulum-resident protein 57 (ERp57), but data about mTG are lacking. We investigated the localization of ERp57 in duodenal biopsies and examined inhibition of TG2, and mTG by competitive, and oxidative molecules. Localization of ERp57 was investigated in duodenal biopsies from CD, and control patients by electron microcopy. Inhibition of TG2 and mTG was analyzed on an in vitro level using a photometric assay. ERp57 was observed within the lamina propria and its abundance within the endoplasmic reticulum (ER) was reduced in CD patients. TG2 was oxidatively inhibited by up to 95% by PX12 (<i>p</i> < 0.001) and L-cystine (<i>p</i> < 0.001), whereas mTG remained unaffected. The reduced presence of ERp57 within the ER of CD biopsies suggests a regulatory function of this protein within CD pathogenesis. PX12 and L-cystine oxidatively inhibit TG2 and might serve as treatment options in CD. mTG is poorly regulated and could contribute to the accumulation of immunogenic peptides within the gut with potential pathogenic effects. |
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| format | Article |
| id | doaj.art-2e581c249f474cca8d3ad99d8ea824e5 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:51Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-2e581c249f474cca8d3ad99d8ea824e52023-11-23T20:22:22ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234224810.3390/ijms23042248Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac DiseaseSebastian Stricker0Silvia Rudloff1Jan De Laffolie2Klaus-Peter Zimmer3Department of Pediatrics, Justus-Liebig-University Giessen, 35392 Giessen, GermanyDepartment of Pediatrics, Justus-Liebig-University Giessen, 35392 Giessen, GermanyDepartment of Pediatrics, Justus-Liebig-University Giessen, 35392 Giessen, GermanyDepartment of Pediatrics, Justus-Liebig-University Giessen, 35392 Giessen, GermanyEnzymatic modification of gliadin peptides by human transglutaminase 2 (TG2) is a central step in celiac disease (CD) pathogenesis. Microbial transglutaminase (mTG) mimics the enzymatic function of TG2 and might play a role in CD. TG2 is inhibited by endogenous oxidative endoplasmic reticulum-resident protein 57 (ERp57), but data about mTG are lacking. We investigated the localization of ERp57 in duodenal biopsies and examined inhibition of TG2, and mTG by competitive, and oxidative molecules. Localization of ERp57 was investigated in duodenal biopsies from CD, and control patients by electron microcopy. Inhibition of TG2 and mTG was analyzed on an in vitro level using a photometric assay. ERp57 was observed within the lamina propria and its abundance within the endoplasmic reticulum (ER) was reduced in CD patients. TG2 was oxidatively inhibited by up to 95% by PX12 (<i>p</i> < 0.001) and L-cystine (<i>p</i> < 0.001), whereas mTG remained unaffected. The reduced presence of ERp57 within the ER of CD biopsies suggests a regulatory function of this protein within CD pathogenesis. PX12 and L-cystine oxidatively inhibit TG2 and might serve as treatment options in CD. mTG is poorly regulated and could contribute to the accumulation of immunogenic peptides within the gut with potential pathogenic effects.https://www.mdpi.com/1422-0067/23/4/2248celiac diseasetransglutaminase 2microbial transglutaminaseTG2 inhibitorERp57 |
| spellingShingle | Sebastian Stricker Silvia Rudloff Jan De Laffolie Klaus-Peter Zimmer Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease International Journal of Molecular Sciences celiac disease transglutaminase 2 microbial transglutaminase TG2 inhibitor ERp57 |
| title | Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease |
| title_full | Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease |
| title_fullStr | Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease |
| title_full_unstemmed | Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease |
| title_short | Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease |
| title_sort | tissue transglutaminase but not microbial transglutaminase is inhibited by exogenous oxidative substances in celiac disease |
| topic | celiac disease transglutaminase 2 microbial transglutaminase TG2 inhibitor ERp57 |
| url | https://www.mdpi.com/1422-0067/23/4/2248 |
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