title: Suppression of StarD7 promotes endoplasmic reticulum stress and induces ROS production.
abstract: StarD7 is an intracellular lipid transport protein identified as up-regulated in the choriocarcinoma JEG-3 cell line. StarD7 facilitates the delivery of phosphatidylcholine (PC) to the mitochondria, and StarD7 knockdown causes a reduction in phospholipid synthesis. Since inhibition of PC synthesis may lead to endoplasmic reticulum (ER) stress we hypothesized that StarD7 may be involved in maintaining cell homeostasis. Here, we examined the effect of StarD7 silencing on ER stress response and on the levels of reactive oxygen species (ROS) in the human hepatoma cell line HepG2. StarD7 knockdown induced alterations in mitochondria and ER morphology. These changes were accompanied with an ER stress response as determined by increased expression of inositol-requiring enzyme 1α (IRE1α), calnexin, glucose regulated protein 78/immunoglobulin heavy chain-binding protein (Grp78/BiP), protein kinase-like ER kinase (PERK) as well as the phosphorylated eukaryotic translation initiation factor 2, subunit 1α (p-eIF2α). Additionally, a downregulation of the tumor suppressor p53 by a degradation mechanism was observed in StarD7 siRNA cells. Furthermore, StarD7 silencing induced ROS generation and reduced cell viability after H2O2exposure. Decreased expression of StarD7 was associated to increased levels of the heme oxygenase-1 (HO-1) and catalase enzymes as well as in catalase enzymatic activity. Finally, no changes in levels of autophagy and apoptosis markers were observed in StarD7 siRNA treated cells respect to control cells. Taken together, these results indicate that StarD7 contributes to modulate cellular redox homeostasis.
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, Haya de la Torre y Medina Allende, X5000HUA Córdoba, Argentina.
authors.forename: Jésica
authors.initials: J
authors.lastname: Flores-Martín
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, Haya de la Torre y Medina Allende, X5000HUA Córdoba, Argentina.
authors.forename: Luciana
authors.initials: L
authors.lastname: Reyna
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, Haya de la Torre y Medina Allende, X5000HUA Córdoba, Argentina.
authors.forename: Magali E
authors.initials: ME
authors.lastname: Ridano
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, Haya de la Torre y Medina Allende, X5000HUA Córdoba, Argentina.
authors.forename: Graciela M
authors.initials: GM
authors.lastname: Panzetta-Dutari
authors.affiliation: Universidad Nacional de Córdoba-Consejo Nacional de Investigaciones Científicas y Técnicas, Facultad de Ciencias Químicas, Departamento de Bioquímica Clínica-Centro de Investigaciones en Bioquímica Clínica e Inmunología, Haya de la Torre y Medina Allende, X5000HUA Córdoba, Argentina. Electronic address: sgenti@fcq.unc.edu.ar.
authors.forename: Susana
authors.initials: S
authors.lastname: Genti-Raimondi
mesh_terms: D001692:Biological Transport; D037281:Calnexin / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects / Q000235:genetics*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006706:Homeostasis / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010713:Phosphatidylcholines / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D059748:Proteolysis / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D015852:Eukaryotic Initiation Factor-2; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D010713:Phosphatidylcholines; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C483475:STARD7 protein, human; D016159:Tumor Suppressor Protein p53; D037281:Calnexin; D006861:Hydrogen Peroxide; D002374:Catalase; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C460640:EIF2AK3 protein, human; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D019892:eIF-2 Kinase; D004722:Endoribonucleases
keywords: Endoplasmic reticulum stress; HepG2 cells; Reactive oxygen species; START domain; StarD7