Neuregulin1β1 protects oligodendrocyte progenitor cells from oxygen glucose deprivation injury induced apoptosis via ErbB4-dependent activation of PI3-kinase/Akt.
Mounting evidence suggests that the injury of oligodendrocyte progenitor cells (OPCs) caused by hypoxia plays a pivotal role in periventricular white matter injury (PWMI) causation. We investigated the potential role of active extracellular domain of Neuregulin1 isotypeβ1 (NRG1β1)/ErbB signaling in protecting OPCs from oxygen glucose deprivation (OGD) induced apoptosis. At different time points, endogenous NRG1β1 protein was analyzed after OGD. Escalating dosages of NRG1β1 were used to treat OPCs with OGD, and the apoptosis was measured, as well as the expression of ErbB receptors, Akt and Erk phosphorylation and caspase3 activation. OGD damage resulted in decreased expression of endogenous NRG1β1. In parallel, NRG1β1 treatment promoted the expression of p-ErbB4 receptor, phosphorylated Akt and inhibited caspase3 activation. Furthermore, the activation of PI3-kinase/Akt by NRG1β1 was ErbB4 dependent. Our data demonstrated that NRG1β1 protected OPCs from OGD induced apoptosis and the possible protective mechanism is linking with ErbB4-dependent activation of PI3-kinase/Akt pathway.
Department of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, 138 Yixueyuan Road, Shanghai, 200032, PR China.
Chongchong
C
Xu
Lei
L
Lv
Guoli
G
Zheng
Beiya
B
Li
Lu
L
Gao
Yan
Y
Sun
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia / Q000502:physiology*; D002470:Cell Survival; D004789:Enzyme Activation / Q000502:physiology; D066246:ErbB Receptors / Q000502:physiology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000172:deficiency*; D020890:Neuregulin-1 / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology*
D020890:Neuregulin-1; C117467:neuregulin beta; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; C587691:Erbb4 protein, rat; D066247:Receptor, ErbB-4; D051057:Proto-Oncogene Proteins c-akt; D053148:Caspase 3; D005947:Glucose