Inducible nitric oxide synthase and nitric oxide production in human fetal astrocytes and microglia: A kinetic analysis

Authors

Minzhen Ding, University of California - Los AngelesFollow
Barbara St. Pierre Schneider, University of Nevada, Las VegasFollow
John F. Parkinson, Berlex Biosciences
Poonam Medberry, Berlex Biosciences
Joyce L. Wong, University of California - Los Angeles
Norma E. Rogers, University of California - Los Angeles
Louis J. Ignarro, University of California - Los Angeles
Jean E. Merrill, Berlex Biosciences

Document Type

Article

Publication Date

4-25-1997

Publication Title

Journal of Biological Chemistry

Volume

272

First page number:

11327

Last page number:

11335

Abstract

The understanding of the induction and regulation of inducible nitric-oxide synthase (iNOS) in human cells may be important in developing therapeutic interventions for inflammatory diseases. In the present study, we not only demonstrated that human fetal mixed glial cultures, as well as enriched microglial cultures, synthesize iNOS and nitric oxide (NO) in response to cytokine stimulation, but also assessed the kinetics of iNOS and NO synthesis in human fetal mixed glial cultures. The iNOS mRNA was expressed within 2 h after stimulation and decreased to base line by 2 days. Significant levels of iNOS protein appeared within 24 h after stimulation and remained elevated during the culture period. A dramatic increase in NO production and NO-mediated events, such as the induction of cyclic guanosine monophosphate (cGMP), NADPH diaphorase activity, and nitrotyrosine occurred 3 days after stimulation, a delay of 48 h from the time of the first expression of iNOS enzyme. This delay of NO production was altered by the addition of tetrahydrobiopterin, but not by the addition of L-arginine, heme, flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), or NADPH. These findings suggest that a post-translational regulatory event might be involved in iNOS-mediated NO production in human glia.

Keywords

Cytokines; Inflammation; Nitric-oxide; Nitric-oxide synthase

Disciplines

Medicine and Health Sciences | Nursing

Language

English

Permissions

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Repository Citation

Ding, M., Schneider, B. S., Parkinson, J. F., Medberry, P., Wong, J. L., Rogers, N. E., Ignarro, L. J., Merrill, J. E. (1997). Inducible nitric oxide synthase and nitric oxide production in human fetal astrocytes and microglia: A kinetic analysis. Journal of Biological Chemistry, 272 11327-11335.