Role of Protein Kinase C in the Expression of Inducible Nitric Oxide Synthase in BV-2 Microglial Cells

Abstract

Microglial cells activated to produce nitric oxide (•NO) are found localized around Aβ plaques in the brains of Alzheimer’s patients1,2. • The mechanism by which they are activated in the progression of the disease is not fully understood. • Lipopolysaccharide (LPS) and gamma interferon (γ-INF) upregulate the levels of inducible nitric oxide synthase (iNOS) in microglial cells, increasing production of •NO3,4,5. • Phorbol myristate acetate (PMA) activates secretases responsible for the formation of Aβ plaques via regulation of protein kinase C (PKC)6. • PKC isoforms have been implicated in the pathways activated by LPS and γ-INF7. • This study was undertaken to determine the PKC isoform involved in the upregulation of iNOS in BV-2 microglial cells by examining the effects of select cell activators (PMA, LPS, γ-INF) and select PKC inhibitors (Ro-31-8220, Go6976, Go6983) on the expression levels of iNOS and PKC isoforms. • Based on initial studies, it was hypothesized that iNOS expression in BV-2 cells was under the control of PKCμ.