title: Activation of ER stress by hydrogen peroxide in C2C12 myotubes.
abstract: The purpose of this study was to examine the link between oxidative stress and endoplasmic reticulum (ER) stress in myogenic cells. C2C12 myotubes were incubated with hydrogen peroxide (H2O2, 200 μM) and harvested 4h or 17 h after the induction of this oxidative stress. A massive upregulation of binding immunoglobulin protein (BiP) was found, indicating the presence of ER stress. Nevertheless, the three branches of the unfolded protein response (UPR) were not activated to the same extent. The double-stranded RNA-dependent protein kinase (PKR)-like ER kinase (PERK) branch was the most activated as shown by the increase of phospho-eukaryotic translation-initiation factor 2α (eIF2α, Ser51) and the mRNA levels of activating transcription factor 4 (ATF4), C/EBP homologous (CHOP) and tribbles homolog 3 (TRB3). The slight increase in the spliced form of X-box binding protein 1 (XBP1s) together with the decrease of the unspliced form (XBP1u) indicated a higher endoribonuclease activity of inositol-requiring 1α (IRE1α). The transcriptional activity of activating transcription factor 6 (ATF6) remained unchanged after incubation with H2O2. The mechanisms by which the three branches of UPR can be specifically regulated by oxidative stress are currently unresolved and need further investigations.
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Pierre
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Caroline
authors.initials: C
authors.lastname: Barbé
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Hélène
authors.initials: H
authors.lastname: Gilson
authors.affiliation: Department of Kinesiology, Exercise Physiology Research Group, KU Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Raymackers
authors.affiliation: Institute of Neuroscience, Université catholique de Louvain, Louvain-la-Neuve, Belgium. Electronic address: marc.francaux@uclouvain.be.
authors.forename: Marc
authors.initials: M
authors.lastname: Francaux
mesh_terms: D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000502:physiology*; D004722:Endoribonucleases / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D051379:Mice; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D019892:eIF-2 Kinase / Q000378:metabolism*
chemical_list: D004722:Endoribonucleases; D006861:Hydrogen Peroxide; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D019892:eIF-2 Kinase; C510185:Ern1 protein, mouse
keywords: Activating transcription factor 6 (ATF6); Binding immunoglobulin protein (BiP); Eukaryotic translation-initiation factor 2α (eIF2α); Oxidative stress; Unfolded protein response (UPR); X-box binding protein 1 spliced (XBP1s)