Journal article

Publication year: 2022

Journal: International Journal of Molecular Sciences

Volume number: 23

Issue number: 4

eISSN: 1422-0067

Open access status: Gold

DOI Link: https://doi.org/10.3390/ijms23042248

Publisher: MDPI

Abstract: 
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 (p < 0.001) and L-cystine (p < 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.

Harvard Citation style: Stricker, S., Rudloff, S., De Laffolie, J. and Zimmer, K. (2022) Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease, International Journal of Molecular Sciences, 23(4), Article 2248. https://doi.org/10.3390/ijms23042248

APA Citation style: Stricker, S., Rudloff, S., De Laffolie, J., & Zimmer, K. (2022). Tissue Transglutaminase but Not Microbial Transglutaminase Is Inhibited by Exogenous Oxidative Substances in Celiac Disease. International Journal of Molecular Sciences. 23(4), Article 2248. https://doi.org/10.3390/ijms23042248