117172 20240319080959.0 doi 10.3390/antiox11030581 sideral 128626 ART-2022-128626 eng Bidooki, S. H. Squalene Loaded Nanoparticles Effectively Protect Hepatic AML12 Cell Lines against Oxidative and Endoplasmic Reticulum Stress in a TXNDC5-Dependent Way 2022 Access copy available to the general public Unrestricted Virgin olive oil, the main source of fat in the Mediterranean diet, contains a substantial amount of squalene which possesses natural antioxidant properties. Due to its highly hydrophobic nature, its bioavailability is reduced. In order to increase its delivery and potentiate its actions, squalene has been loaded into PLGA nanoparticles (NPs). The characterization of the resulting nanoparticles was assessed by electron microscopy, dynamic light scattering, zeta potential and highperformance liquid chromatography. Reactive oxygen species (ROS) generation and cell viability assays were carried out in AML12 (alpha mouse liver cell line) and a TXNDC5-deficient AML12 cell line (KO), which was generated by CRISPR/cas9 technology. According to the results, squalene was successfully encapsulated in PLGA NPs, and had rapid and efficient cellular uptake at 30 µM squalene concentration. Squalene reduced ROS in AML12, whereas ROS levels increased in KO cells and improved cell viability in both when subjected to oxidative stress by significant induction of Gpx4. Squalene enhanced cell viability in ER-induced stress by decreasing Ern1 or Eif2ak3 expressions. In conclusion, TXNDC5 shows a crucial role in regulating ER-induced stress through different signaling pathways, and squalene protects mouse hepatocytes from oxidative and endoplasmic reticulum stresses by several molecular mechanisms depending on TXNDC5. © 2022 by the authors. Licensee MDPI, Basel, Switzerland. info:eu-repo/grantAgreement/ES/DGA-FSE/B16-20R info:eu-repo/grantAgreement/ES/MICINN-ISCIIII-FEDER/PID2019-104915RB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 7.0 2022 BIOCHEMISTRY & MOLECULAR BIOLOGY 46 / 285 = 0.161 2022 Q1 T1 FOOD SCIENCE & TECHNOLOGY 13 / 142 = 0.092 2022 Q1 T1 CHEMISTRY, MEDICINAL 6 / 60 = 0.1 2022 Q1 T1 1.084 2022 Biochemistry 2022 Q1 Clinical Biochemistry 2022 Q1 Food Science 2022 Q1 Physiology 2022 Q1 Molecular Biology 2022 Q2 Cell Biology 2022 Q2 8.8 2022 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Alejo, T. Universidad de Zaragoza (orcid)0000-0002-9324-0446 Sánchez-Marco, J. (orcid)0000-0002-9023-741X Martínez-Beamonte, R. Universidad de Zaragoza (orcid)0000-0002-8100-5596 Abuobeid, R. Burillo, J. C. Lasheras, R. Sebastian, V. Universidad de Zaragoza (orcid)0000-0002-6873-5244 Rodríguez-Yoldi, M. J. Universidad de Zaragoza (orcid)0000-0002-3595-7668 Arruebo, M. Universidad de Zaragoza (orcid)0000-0003-3165-0156 Osada, J. Universidad de Zaragoza (orcid)0000-0002-8251-8457 1012 410 Universidad de Zaragoza Dpto. Farmac.Fisiol.y Med.L.F. Área Fisiología 5005 555 Universidad de Zaragoza Dpto. Ing.Quím.Tecnol.Med.Amb. Área Ingeniería Química 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 1002 050 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Biología Celular 11, 3 (2022), 581 [22 pp] Antioxidants Antioxidants 2076-3921 5010705 http://zaguan.unizar.es/record/117172/files/texto_completo.pdf Versión publicada 2818797 http://zaguan.unizar.es/record/117172/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:117172 articulos driver 2024-03-18-13:56:23 ARTICLE