000129631 001__ 129631
000129631 005__ 20240118091947.0
000129631 0247_ $$2doi$$a10.3390/ijms242417131
000129631 0248_ $$2sideral$$a135891
000129631 037__ $$aART-2023-135891
000129631 041__ $$aeng
000129631 100__ $$aBidooki, Seyed Hesamoddin$$uUniversidad de Zaragoza
000129631 245__ $$aEndoplasmic Reticulum Protein TXNDC5 Interacts with PRDX6 and HSPA9 to Regulate Glutathione Metabolism and Lipid Peroxidation in the Hepatic AML12 Cell Line
000129631 260__ $$c2023
000129631 5060_ $$aAccess copy available to the general public$$fUnrestricted
000129631 5203_ $$aNon-alcoholic fatty liver disease or steatosis is an accumulation of fat in the liver. Increased amounts of non-esterified fatty acids, calcium deficiency, or insulin resistance may disturb endoplasmic reticulum (ER) homeostasis, which leads to the abnormal accumulation of misfolded proteins, activating the unfolded protein response. The ER is the primary location site for chaperones like thioredoxin domain-containing 5 (TXNDC5). Glutathione participates in cellular oxidative stress, and its interaction with TXNDC5 in the ER may decrease the disulfide bonds of this protein. In addition, glutathione is utilized by glutathione peroxidases to inactivate oxidized lipids. To characterize proteins interacting with TXNDC5, immunoprecipitation and liquid chromatography–mass spectrometry were used. Lipid peroxidation, reduced glutathione, inducible phospholipase A2 (iPLA2) and hepatic transcriptome were assessed in the AML12 and TXNDC5-deficient AML12 cell lines. The results showed that HSPA9 and PRDX6 interact with TXNDC5 in AML12 cells. In addition, TXNDC5 deficiency reduced the protein levels of PRDX6 and HSPA9 in AML12. Moreover, lipid peroxidation, glutathione and iPLA2 activities were significantly decreased in TXNDC5-deficient cells, and to find the cause of the PRDX6 protein reduction, proteasome suppression revealed no considerable effect on it. Finally, hepatic transcripts connected to PRDX6 and HSPA9 indicated an increase in the Dnaja3, Mfn2 and Prdx5 and a decrease in Npm1, Oplah, Gstp3, Gstm6, Gstt1, Serpina1a, Serpina1b, Serpina3m, Hsp90aa1 and Rps14 mRNA levels in AML12 KO cells. In conclusion, the lipid peroxidation system and glutathione mechanism in AML12 cells may be disrupted by the absence of TXNDC5, a novel protein–protein interacting partner of PRDX6 and HSPA9.
000129631 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B16-23R$$9info:eu-repo/grantAgreement/ES/ISCIII-EDRF/PT17-0019$$9info:eu-repo/grantAgreement/ES/MICINN AEI/PID2019-104915RB-I00
000129631 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000129631 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000129631 700__ $$0(orcid)0000-0002-9023-741X$$aSánchez-Marco, Javier
000129631 700__ $$0(orcid)0000-0002-8100-5596$$aMartínez-Beamonte, Roberto$$uUniversidad de Zaragoza
000129631 700__ $$aHerrero-Continente, Tania
000129631 700__ $$0(orcid)0000-0002-0108-1004$$aNavarro, María A.$$uUniversidad de Zaragoza
000129631 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, María J.$$uUniversidad de Zaragoza
000129631 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, Jesús$$uUniversidad de Zaragoza
000129631 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000129631 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000129631 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000129631 773__ $$g24, 24 (2023), 17131$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000129631 8564_ $$s2576858$$uhttps://zaguan.unizar.es/record/129631/files/texto_completo.pdf$$yVersión publicada
000129631 8564_ $$s2752970$$uhttps://zaguan.unizar.es/record/129631/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000129631 909CO $$ooai:zaguan.unizar.es:129631$$particulos$$pdriver
000129631 951__ $$a2024-01-18-09:12:27
000129631 980__ $$aARTICLE