Figure 9

Novel pathway of PKC and MAPK-mediated transcriptional activation of iNOS in LPS-treated BV-2 cells. LPS activates cPKC and nPKC isoforms in BV-2 cells. Activation of PKC δ, η, α and β leads to ERK1/2 phosphorylation, whereas activation of PKC β and θ mainly phosphorylates p38. Phosphorylation of ERK1/2 and p38 converges to the activation of NF-κB and results in upregulation of iNOS and production of NO. NO can then react with superoxide to form the potent oxidant, peroxynitrite, culminating in cell death. The heavy arrows indicate that PKC δ and β are the two principal PKC isoforms involved in the signaling pathway proposed.