Suppression of StarD7 promotes endoplasmic reticulum stress and induces ROS production

RIDANO, M.E; REYNA L; GENTI RAIMONDI S; FLORES MARTIN J; PANZETTA DUTARI G

FREE RADICAL BIOLOGY AND MEDICINE

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2016 vol. 99 p. 286 - 295

0891-5849

StarD7 transcript encodes an intracellular lipid transport protein identified as an up-regulated gene in the choriocarcinoma JEG-3 cell line. It 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 measured by augmented 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). Moreover, downregulation of the tumor suppressor p53 by a degradation mechanism was established in StarD7 siRNA cells. Additionally, StarD7 silencing induced ROS generation and reduced cell viability after H2O2 exposure. Diminished StarD7 expression was associated to increased levels of the heme oxygenase-1 (HO-1) and catalase enzymes as well as in catalase enzyme activity. Finally, no changes in the 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 maintain cellular redox homeostasis.