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In this study, effects of selective PTP1B inhibition using MSI-1436 on cellular apoptosis, oxidative stress, mitochondrial dysfunction and ER stress have been assessed using an <jats:italic>in vitro<\/jats:italic> model of Tunicamycin induced ER stress in HepG2 cell line. Inhibition of PTP1B using MSI-1436 significantly increased cell viability and reduced the number of apoptotic cells as well as the expression of key apoptosis initiators and effectors. MSI-1436 further mitigated ER stress, by downregulating the expression of IRE1, ATF6 and PERK transcripts, all being key ER stress sensors. Interestingly, MSI-1436 inhibited the XBP1 splicing, and thus its UPR-associated transcriptional activity. PTP1B inhibition further enabled to restore proper mitochondrial biogenesis, by improving transmembrane potential, and diminishing intracellular ROS while restoring of endogenous antioxidant enzymes genes expression. PTP1B inhibition using MSI-1436 could improve cellular apoptosis and metabolic integrity through the mitigation of ER and mitochondrial stress signalling pathways, and excessive ROS accumulation. This strategy may be useful for the treatment of metabolic disorders including IR, NAFLD and diabetes.<\/jats:p>","DOI":"10.1371\/journal.pone.0278566","type":"journal-article","created":{"date-parts":[[2023,1,18]],"date-time":"2023-01-18T03:58:16Z","timestamp":1674014296000},"page":"e0278566","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":13,"title":["The PTP1B selective inhibitor MSI-1436 mitigates Tunicamycin-induced ER stress in human hepatocarcinoma cell line through XBP1 splicing modulation"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-8706","authenticated-orcid":true,"given":"Lynda","family":"Bourebaba","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6109-2736","authenticated-orcid":true,"given":"Sai Santosh Babu","family":"Komakula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3723-3003","authenticated-orcid":true,"given":"Nabil","family":"Adrar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Krzysztof","family":"Marycz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,1,17]]},"reference":[{"key":"pone.0278566.ref001","first-page":"1","article-title":"Molecular Mechanisms of Liver Development: Lessons From Animal Models","author":"N. 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Goldstein","year":"2005","journal-title":"Antioxidants & Redox Signaling"},{"issue":"24","key":"pone.0278566.ref032","doi-asserted-by":"crossref","first-page":"21938","DOI":"10.1074\/jbc.C100109200","article-title":"Insulin-stimulated Hydrogen Peroxide Reversibly Inhibits Protein-tyrosine Phosphatase 1B in Vivo and Enhances the Early Insulin Action Cascade","volume":"276","author":"K. Mahadev","year":"2001","journal-title":"Journal of Biological Chemistry"},{"issue":"3","key":"pone.0278566.ref033","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1007\/s00125-012-2782-z","article-title":"Endoplasmic reticulum stress upregulates protein tyrosine phosphatase 1B and impairs glucose uptake in cultured myotubes","volume":"56","author":"E. Panzhinskiy","year":"2013","journal-title":"Diabetologia"},{"issue":"6","key":"pone.0278566.ref034","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.tips.2017.03.004","article-title":"Targeting Tyrosine Phosphatases: Time to End the Stigma","volume":"38","author":"S. M. Stanford","year":"2017","journal-title":"Trends in Pharmacological Sciences"},{"issue":"11","key":"pone.0278566.ref035","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.4155\/fmc-2016-0064","article-title":"Recent advances in the development of protein tyrosine phosphatase 1B inhibitors for Type 2 diabetes.","volume":"8","author":"S. Qian","year":"2016","journal-title":"Future Medicinal Chemistry"},{"issue":"12","key":"pone.0278566.ref036","first-page":"E2543","article-title":"A natural product inhibits the initiation of alpha-synuclein aggregation and suppresses its toxicity (vol 114, pg E1009, 2017).","volume":"114","author":"M. 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Hsu","year":"2020","journal-title":"Redox Biology"},{"issue":"4","key":"pone.0278566.ref046","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1309\/1PX2LMPQUH1EE12U","article-title":"The Use of Protein Tyrosine Phosphatase 1B and Insulin Receptor Immunostains to Differentiate Nonalcoholic From Alcoholic Steatohepatitis in Liver Biopsy Specimens","volume":"123","author":"S. O. Sanderson","year":"2005","journal-title":"American Journal of Clinical Pathology"},{"issue":"3","key":"pone.0278566.ref047","doi-asserted-by":"crossref","first-page":"590","DOI":"10.2337\/db08-0913","article-title":"Liver-Specific Deletion of Protein-Tyrosine Phosphatase 1B (PTP1B) Improves Metabolic Syndrome and Attenuates Diet-Induced Endoplasmic Reticulum Stress.","volume":"58","author":"M. Delibegovic","year":"2009","journal-title":"Diabetes"},{"issue":"7","key":"pone.0278566.ref048","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nchembio.1528","article-title":"Targeting the disordered C terminus of PTP1B with an allosteric inhibitor","volume":"10","author":"N. Krishnan","year":"2014","journal-title":"Nature Chemical Biology"},{"issue":"1","key":"pone.0278566.ref049","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1038\/s41536-017-0008-1","article-title":"The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues","volume":"2","author":"A. M. Smith","year":"2017","journal-title":"Npj Regenerative Medicine"},{"issue":"3","key":"pone.0278566.ref050","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jhep.2004.05.006","article-title":"A novel aminosterol reverses diabetes and fatty liver disease in obese mice","volume":"41","author":"N. 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