000136268 001__ 136268
000136268 005__ 20240731105611.0
000136268 0247_ $$2doi$$a10.3390/ijms25137128
000136268 0248_ $$2sideral$$a139283
000136268 037__ $$aART-2024-139283
000136268 041__ $$aeng
000136268 100__ $$aBidooki, Seyed Hesamoddin$$uUniversidad de Zaragoza
000136268 245__ $$aTXNDC5 Plays a Crucial Role in Regulating Endoplasmic Reticulum Activity through Different ER Stress Signaling Pathways in Hepatic Cells
000136268 260__ $$c2024
000136268 5060_ $$aAccess copy available to the general public$$fUnrestricted
000136268 5203_ $$aThe pathogenesis of non-alcoholic fatty liver disease (NAFLD) is influenced by a number of variables, including endoplasmic reticulum stress (ER). Thioredoxin domain-containing 5 (TXNDC5) is a member of the protein disulfide isomerase family and acts as an endoplasmic reticulum (ER) chaperone. Nevertheless, the function of TXNDC5 in hepatocytes under ER stress remains largely uncharacterized. In order to identify the role of TXNDC5 in hepatic wild-type (WT) and TXNDC5-deficient (KO) AML12 cell lines, tunicamycin, palmitic acid, and thapsigargin were employed as stressors. Cell viability, mRNA, protein levels, and mRNA splicing were then assayed. The protein expression results of prominent ER stress markers indicated that the ERN1 and EIF2AK3 proteins were downregulated, while the HSPA5 protein was upregulated. Furthermore, the ATF6 protein demonstrated no significant alterations in the absence of TXNDC5 at the protein level. The knockout of TXNDC5 has been demonstrated to increase cellular ROS production and its activity is required to maintain normal mitochondrial function during tunicamycin-induced ER stress. Tunicamycin has been observed to disrupt the protein levels of HSPA5, ERN1, and EIF2AK3 in TXNDC5-deficient cells. However, palmitic acid has been observed to disrupt the protein levels of ATF6, HSPA5, and EIF2AK3. In conclusion, TXNDC5 can selectively activate distinct ER stress pathways via HSPA5, contingent on the origin of ER stress. Conversely, the absence of TXNDC5 can disrupt the EIF2AK3 cascade.
000136268 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B16-23R$$9info:eu-repo/grantAgreement/ES/ISCIII/CB06-03-1012
000136268 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000136268 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000136268 700__ $$0(orcid)0000-0002-8442-8041$$aBarranquero, Cristina
000136268 700__ $$0(orcid)0000-0002-9023-741X$$aSánchez-Marco, Javier
000136268 700__ $$0(orcid)0000-0002-8100-5596$$aMartínez-Beamonte, Roberto$$uUniversidad de Zaragoza
000136268 700__ $$0(orcid)0000-0002-3595-7668$$aRodríguez-Yoldi, María J.$$uUniversidad de Zaragoza
000136268 700__ $$0(orcid)0000-0002-0108-1004$$aNavarro, María A.$$uUniversidad de Zaragoza
000136268 700__ $$aFernandes, Susana C. M.
000136268 700__ $$0(orcid)0000-0002-8251-8457$$aOsada, Jesús$$uUniversidad de Zaragoza
000136268 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000136268 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000136268 7102_ $$11002$$2050$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Biología Celular
000136268 773__ $$g25, 13 (2024), 7128 [26 pp.]$$pInt. j. mol. sci.$$tInternational Journal of Molecular Sciences$$x1661-6596
000136268 8564_ $$s10099170$$uhttps://zaguan.unizar.es/record/136268/files/texto_completo.pdf$$yVersión publicada
000136268 8564_ $$s2737122$$uhttps://zaguan.unizar.es/record/136268/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000136268 909CO $$ooai:zaguan.unizar.es:136268$$particulos$$pdriver
000136268 951__ $$a2024-07-31-09:21:53
000136268 980__ $$aARTICLE