The control of reactive oxygen species production by SHP-1 in oligodendrocytes

摘要: We have previously described reduced myelination and corresponding myelin basic protein (MBP) expression in the central nervous system of Src homology 2 domain-containing tyrosine phosphatase 1 (SHP-1) deficient motheaten (me/me) mice compared with normal littermate controls. Deficiency MBP both brains spinal cords correlated mRNA levels vivo purified oligodendrocytes vitro. Therefore, SHP-1 activity seems to be a critical regulator oligodendrocyte gene function. Consistent this role, study demonstrates that SHP-1-depleted N20.1 cells produce higher reactive oxygen species (ROS) exhibit markers increased oxidative stress. In agreement these findings, we demonstrate production ROS coincides ROS-induced signaling pathways known affect oligodendrocytes. Antioxidant treatment SHP-1-deficient reversed pathological changes cells, decreased nuclear factor (erythroid-2)-related (Nrf2) responsive gene, heme oxygenase-1 (HO-1). Furthermore, is expressed human white matter oligodendrocytes, there subset multiple sclerosis subjects deficiency normal-appearing matter. These studies reveal controlled by relate susceptibility developmental defects inflammatory demyelinating diseases. GLIA 2015;63:1753–1771