PMID- 37685847 OWN - NLM STAT- MEDLINE DCOM- 20230911 LR - 20230911 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 17 DP - 2023 Aug 22 TI - The Combination of Gold and Silver Food Nanoparticles with Gluten Peptides Alters the Autophagic Pathway in Intestinal Crypt-like Cells. LID - 10.3390/ijms241713040 [doi] LID - 13040 AB - Metallic nanoparticles (mNPs) are widely used as food additives and can interact with gliadin triggering an immune response, but evaluation of the effects on crypts, hypertrophic in celiac subjects, is still lacking. This study evaluated the effects of gold and silver mNPs in combination with gliadin on crypt-like cells (HIEC-6). Transmission electron microscopy (TEM) was used to evaluate gliadin-mNP aggregates in cells. Western blot and immunofluorescence analysis assessed autophagy-related molecule levels (p62, LC3, beclin-1, EGFR). Lysosome functionality was tested with acridine orange (AO) and Magic Red assays. TEM identified an increase in autophagic vacuoles after exposure to gliadin + mNPs, as also detected by significant increments in LC3-II and p62 expression. Immunofluorescence confirmed the presence of mature autophagosomes, showing LC3 and p62 colocalization, indicating an altered autophagic flux, further assessed with EGFR degradation, AO and Magic Red assays. The results showed a significant reduction in lysosomal enzyme activity and a modest reduction in acidity. Thus, gliadin + mNPs can block the autophagic flux inducing a lysosomal defect. The alteration of this pathway, essential for cell function, can lead to cell damage and death. The potential effects of this copresence in food should be further characterized to avoid a negative impact on celiac disease subjects. FAU - Mancuso, Clara AU - Mancuso C AUID- ORCID: 0000-0001-7464-1749 AD - School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. AD - Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC J1H 5H4, Canada. FAU - Tremblay, Eric AU - Tremblay E AD - Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC J1H 5H4, Canada. FAU - Gnodi, Elisa AU - Gnodi E AUID- ORCID: 0000-0002-4390-6633 AD - School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. FAU - Jean, Steve AU - Jean S AUID- ORCID: 0000-0001-6881-5781 AD - Department of Immunology and Cell Biology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC J1H 5H4, Canada. FAU - Beaulieu, Jean-Francois AU - Beaulieu JF AUID- ORCID: 0000-0002-8977-3629 AD - Laboratory of Intestinal Physiopathology, Faculty of Medicine and Health Sciences, Universite de Sherbrooke, Sherbrooke, QC J1H 5H4, Canada. FAU - Barisani, Donatella AU - Barisani D AUID- ORCID: 0000-0003-4592-6221 AD - School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy. LA - eng GR - MOP-136991/CAPMC/CIHR/Canada GR - PJT-162423/CAPMC/CIHR/Canada PT - Journal Article DEP - 20230822 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 7440-57-5 (Gold) RN - 8002-80-0 (Glutens) RN - 3M4G523W1G (Silver) RN - 9007-90-3 (Gliadin) RN - F30N4O6XVV (Acridine Orange) RN - EC 2.7.10.1 (ErbB Receptors) SB - IM MH - Humans MH - *Gold MH - Glutens MH - Silver MH - Gliadin MH - Autophagy MH - Acridine Orange MH - *Nanoparticles MH - ErbB Receptors PMC - PMC10487529 OTO - NOTNLM OT - autophagy OT - celiac disease OT - dietary metallic nanoparticles OT - food additives OT - gluten peptides OT - lysosome dysfunction COIS- The authors declare no conflict of interest. EDAT- 2023/09/09 11:43 MHDA- 2023/09/11 06:42 PMCR- 2023/08/22 CRDT- 2023/09/09 01:10 PHST- 2023/07/31 00:00 [received] PHST- 2023/08/11 00:00 [revised] PHST- 2023/08/18 00:00 [accepted] PHST- 2023/09/11 06:42 [medline] PHST- 2023/09/09 11:43 [pubmed] PHST- 2023/09/09 01:10 [entrez] PHST- 2023/08/22 00:00 [pmc-release] AID - ijms241713040 [pii] AID - ijms-24-13040 [pii] AID - 10.3390/ijms241713040 [doi] PST - epublish SO - Int J Mol Sci. 2023 Aug 22;24(17):13040. doi: 10.3390/ijms241713040.