FIGURE 8.

The schematic depicts how NO signaling does induce CNTF and GFAP expression in astrocytes. NO induces sGC activation that produces intracellular cGMP from GTP hydrolysis resulting in the activation of PKG and CREB. Activated PKG induces the phosphorylation of p38 MAPK and ERK1/2 that consequently leads to ATF2 phosphorylation and the activation of COX-2 that provides ligands for PPAR-γ translocation. The chromatin accessibility of activated CREB induces interactions of PPAR-γ and ATF2 to the CNTF gene promoter. Subsequently, secreted CNTF induces JAK2-dependent phosphorylation of STAT3, and its interaction with activated CREB and ATF2 induces GFAP expression in astrocytes in an autocrine manner. Likewise, cytokine induced inducible nitric-oxide synthase (NOS-II) expression thus NO production mimics the effect of GSNO in astrocytes. Pol II, polymerase II.