Squalene Loaded Nanoparticles Effectively Protect Hepatic AML12 Cell Lines against Oxidative and Endoplasmic Reticulum Stress in a TXNDC5-Dependent Way

Bidooki, S. H. ; Alejo, T. (Universidad de Zaragoza) ; Sánchez-Marco, J. ; Martínez-Beamonte, R. (Universidad de Zaragoza) ; Abuobeid, R. ; Burillo, J. C. ; Lasheras, R. ; Sebastian, V. (Universidad de Zaragoza) ; Rodríguez-Yoldi, M. J. (Universidad de Zaragoza) ; Arruebo, M. (Universidad de Zaragoza) ; Osada, J. (Universidad de Zaragoza)

Resumen: 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.

Idioma: Inglés

DOI: 10.3390/antiox11030581

Año: 2022

Publicado en: Antioxidants 11, 3 (2022), 581 [22 pp]
ISSN: 2076-3921

Factor impacto JCR: 7.0 (2022)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 46 / 285 = 0.161 (2022) - Q1 - T1
Categ. JCR: FOOD SCIENCE & TECHNOLOGY rank: 13 / 142 = 0.092 (2022) - Q1 - T1
Categ. JCR: CHEMISTRY, MEDICINAL rank: 6 / 60 = 0.1 (2022) - Q1 - T1

Factor impacto CITESCORE: 8.8 - Biochemistry, Genetics and Molecular Biology (Q1)

Factor impacto SCIMAGO: 1.084 - Biochemistry (Q1) - Clinical Biochemistry (Q1) - Food Science (Q1) - Physiology (Q1) - Molecular Biology (Q2) - Cell Biology (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA-FSE/B16-20R
Financiación: info:eu-repo/grantAgreement/ES/MICINN-ISCIIII-FEDER/PID2019-104915RB-I00

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)
Área (Departamento): Área Biología Celular (Dpto. Bioq.Biolog.Mol. Celular)