{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T01:39:35Z","timestamp":1790127575991,"version":"4.0.1"},"reference-count":58,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T00:00:00Z","timestamp":1652054400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp; Molecular Tox"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The present study examined the wheat protein gliadin\u2010induced oxidative and nitrosative stress and its downstream responses in human intestinal HCT\u2010116 and HT\u201029 cells. The beneficial role of dietary phytochemical curcumin and role of multifunctional enzyme Apurinic\/aprymidinic endonuclease 1 (APE1) a major player involved in the base excision repair (BER)\u2010pathway in gliadin intolerant intestinal HCT\u2010116 and HT\u201029 cell lines were evaluated as an in vitro model study. The cultured cells were exposed to gliadin protein, H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub>, and curcumin followed by the assessment of oxidative stress and the consequences were measured using spectrophotometric, PCR, flow cytometer, Western blotting, confocal microscopy, and other methods. Results demonstrate that a 3\u2009h pretreatment of curcumin, followed by the treatment of gliadin protein for 24\u2009h time period protected both the HCT\u2010116 and HT\u201029 cells <jats:italic>via<\/jats:italic>: (i) decreasing the ROS\/RNS, restoring the mitochondrial transmembrane potential; (ii) re\u2010establishing the cellular antioxidant defense system (superoxide dismutase, catalase, and GSH); (iii) enhancing the functions of APE1 viz. endonuclease activity and redox activation of transcription factor Nrf\u20102, the later binds with the antioxidant response elements (ARE) and activates downstream targets involved in cell survival. The cross\u2010talk between APE1 and Nrf\u20102 was also established using immunofluorescence imaging and co\u2010immunoprecipitation assays. In conclusion, gliadin protein induces oxidative\/nitrosative stress, mitochondrial dysfunction and it damages cellular biomolecules in the intestinal cells. Hence it can be attributed to the tissue damage and disease pathogenesis in wheat intolerance\u2010associated intestinal diseases. The gliadin\u2010induced stress and its consequences are significantly reduced by the pretreatment of curcumin via BER\u2010pathway and ARE\u2010pathway; which is evident through the interaction between these two essential proteins. Hence suggesting for the intervention of curcumin and other natural dietary phytochemicals\u2010based disease management and treatment of gliadin intolerance associated intestinal diseases like celiac disease.<\/jats:p>","DOI":"10.1002\/jbt.23096","type":"journal-article","created":{"date-parts":[[2022,5,9]],"date-time":"2022-05-09T12:44:36Z","timestamp":1652100276000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Gliadin induced oxidative stress and altered cellular responses in human intestinal cells: An in\u2010vitro study to understand the cross\u2010talk between the transcription factor Nrf\u20102 and multifunctional APE1 enzyme"],"prefix":"10.1002","volume":"36","author":[{"given":"Kunj Bihari","family":"Gupta","sequence":"first","affiliation":[{"name":"Department of Microbiology, School of Biological Sciences Central University of Punjab  Bathinda Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monisha","family":"Dhiman","sequence":"additional","affiliation":[{"name":"Department of Microbiology, School of Biological Sciences Central University of Punjab  Bathinda Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6310-725X","authenticated-orcid":false,"given":"Anil Kumar","family":"Mantha","sequence":"additional","affiliation":[{"name":"Department of Zoology, School of Biological Sciences Central University of Punjab  Bathinda Punjab India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,5,9]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2229-10-1"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2017.06.037"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13155"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cofs.2019.02.003"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2018.06.020"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41424-018-0031-6"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2198"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2008.2194"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbf.3100"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00630-07"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcme.2016.05.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/801418"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.23.13422"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcs.2018.03.012"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-018-0233-3"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M501977200"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/15321810500403722"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11011-017-0093-2"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1004516"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000302"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2009.08.008"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-161086"},{"key":"e_1_2_10_24_1","first-page":"121","volume-title":"Methods in Enzymology","author":"Aebi H.","year":"1984"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pestbp.2013.07.006"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.378"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-8981(03)00003-2"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.2203\/dose-response.10-002.Siddique"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2020.112690"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2008.03.052"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0907539106"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23018"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22640"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fm.2006.07.004"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms151120518"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu7125541"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.12.048"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/6150145"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/10408398.2012.659818"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1080\/00365520500235334"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2009.183608"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.26217"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871527314666150202152436"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1515\/jomb-2017-0017"},{"key":"e_1_2_10_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.05.037"},{"key":"e_1_2_10_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10753-020-01383-x"},{"key":"e_1_2_10_47_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.104.073312"},{"key":"e_1_2_10_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imr.2016.07.004"},{"key":"e_1_2_10_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clinbiochem.2009.06.009"},{"key":"e_1_2_10_50_1","doi-asserted-by":"publisher","DOI":"10.1590\/S0001-37652012000100018"},{"issue":"8","key":"e_1_2_10_51_1","first-page":"1960","volume":"19","author":"Szaflarska\u2010Pop\u0142awska A.","year":"2010","journal-title":"Biomarkers"},{"key":"e_1_2_10_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/nu4040243"},{"key":"e_1_2_10_53_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-017-3186-7"},{"key":"e_1_2_10_54_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9060550"},{"key":"e_1_2_10_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2010.01473.x"},{"key":"e_1_2_10_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2012.10.001"},{"key":"e_1_2_10_57_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24040708"},{"key":"e_1_2_10_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.10.007"},{"key":"e_1_2_10_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cotox.2016.09.001"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23096","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.23096","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.23096","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,23]],"date-time":"2023-08-23T07:52:01Z","timestamp":1692777121000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.23096"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,9]]},"references-count":58,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2022,8]]}},"alternative-id":["10.1002\/jbt.23096"],"URL":"https:\/\/doi.org\/10.1002\/jbt.23096","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,9]]},"assertion":[{"value":"2021-11-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-04-25","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-05-09","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e23096"}}