title: Catalpol Protects Pre-Myelinating Oligodendrocytes against Ischemia-induced Oxidative Injury through ERK1/2 Signaling Pathway.
abstract: The vulnerability of pre-myelinating oligodendrocytes (PreOLs) to ischemic injury plays an important role in the pathogenesis and progression of perinatal white matter injury. Although oxidative stress is thought to be a major pathogenic mechanism predisposing the PreOLs to injury, no effective therapies have been identified to date. The present study aimed to investigate the direct protective effects of catalpol, a potent antioxidant and free radical scavenger, on ischemia-induced oxidative damage in PreOLs and to explore whether the ERK1/2 signaling pathway contributed to the protection provided by catalpol. Primary cultures of PreOLs exposed to oxygen-glucose deprivation (OGD) followed by reperfusion were used as an in vitro model of ischemia. Pretreatment with 0.5 mM catalpol for 1 h prior to OGD treatment significantly reversed ischemia-induced apoptosis in PreOLs and myelination deficits by inhibiting intracellular Ca2+increase, reducing mitochondrial damage, and ameliorating overproduction of reactive oxygen species (ROS). The expression levels of phosphorylated ERK1/2 (p-ERK1/2) and activated poly-ADP-ribose polymerase-1 (PARP-1) were also markedly decreased by catalpol treatment. Blocking the ERK1/2 signaling pathway with the MEK inhibitor U0126 and catalpol significantly protected PreOLs from ROS-mediated apoptosis under OGD. Taken together, these results suggest that catalpol protects PreOLs against ischemia-induced oxidative injury through ERK1/2 signaling pathway. Catalpol may be a candidate for treating ischemic white matter damage.
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing, China.
authors.forename: Qiyan
authors.initials: Q
authors.lastname: Cai
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Ma
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing, China.
authors.forename: Chengren
authors.initials: C
authors.lastname: Li
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing, China.
authors.forename: Yanping
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Chongqing Key Laboratory of Neurobiology, Department of Histology and Embryology, College of Basic Medicine, The Third Military Medical University, Chongqing, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism; D015153:Blotting, Western; D005434:Flow Cytometry; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D057888:Iridoid Glucosides / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008315:Malondialdehyde / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism
chemical_list: D057888:Iridoid Glucosides; D017382:Reactive Oxygen Species; C078040:catalpol; D008315:Malondialdehyde; D001092:Arachidonate 12-Lipoxygenase; D005947:Glucose; D010100:Oxygen
keywords: ERK1/2; catalpol; oxidative stress; oxygen-glucose deprivation; pre-myelinating oligodendrocytes