J Korean Neurosurg Soc.  1995 Dec;24(12):1455-1462.

The Effect of Phorbol Myristate Actate on the Synthesis of Nitric Oxide in Murine Microglial Cells

• Rim GN
• Kim JM
• Chung HT

Abstract

In this study, the effect of phorbol ester on the synthesis of nitric oxide(NO) in murine microglial cells was examined. Phorbol 12-myristate 13-acetate(PMA), a protein kinase C(PKC) activator, alone had no effect, whereas PMA with recombinant interferon-gamma(rIFN-gamma) synergistically increased NO synthesis in murine microglial cells. The maximal effect of PMA in the increase of NO synthesis always fit with the range for rull activation of PKC in these cells. The increase of NO synthesis was reflected as increased amount of inducible NO synthase(iNOS) mRNA by Northern blotting. Treatment of PKC inhibitors such as staurosporine(STSN) or polymxin B decreased rIFN-gamma plus PMA-stimulated NO synthesis. Further, prolonged incubation of the cells with PMA, which down regulate PKC activity, abolished synergistic cooperative effect with IFN-gamma. N(G)-monomethyl-L arginine monohydrate(NGMMA), an analogue of L-arginine, and arginase inhibited rIFN-gamma plus PMA-induced NO production in murine microglial cells. On the basis of these observations we conclude that PKC might not be involved in the expression of iNOS, but instead, might be involved in the post-transcriptional modification of iNOS mRNA.

Keyword

Microglia; Astrocyte; Nitric oxide; Protein kinase C; Inducible nitric oxide synthase

MeSH Terms

Arginase
Arginine
Astrocytes
Blotting, Northern
Microglia
Myristic Acid*
Nitric Oxide Synthase Type II
Nitric Oxide*
Protein Kinase C
Protein Kinases
RNA, Messenger
Arginase
Arginine
Myristic Acid
Nitric Oxide
Nitric Oxide Synthase Type II
Protein Kinase C
Protein Kinases
RNA, Messenger