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Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures.
Brain Res. 1996 Aug 05; 729(1):102-9.BR

Abstract

Nitric oxide (NO) produced by glial cells has been implicated in the neuropathogenesis of various diseases. However, the signaling transduction pathway(s) for the production of NO in these cells is not well understood. To test whether protein tyrosine kinases (PTKs) are required for signaling events of NO production in glial cells, this study examined the effects of genistein and tyrphostin A25, two potent inhibitors of PTKs, on the production of NO in mouse primary mixed glia, microglia-enriched or astrocyte-enriched cultures exposed to lipopolysaccharide (LPS) or a combination of LPS and interferon-gamma (IFN gamma). LPS induced a dose-dependent increase in NO production from the mixed glia cultures. The LPS-induced NO production was significantly enhanced by stimulating the cells with IFN gamma. Genistein or tyrphostin A25 inhibited the production of NO in both LPS- and IFN gamma/LPS-stimulated mixed glia cultures. The production of NO in the stimulated microglia-enriched or astrocyte-enriched cultures was also inhibited by tyrphostin A25. To verify the cellular sources of NO, immunocytochemical staining of inducible NO synthase (iNOS) was followed by staining with the microglia marker Mac-1 or the astrocyte marker glial fibrillary acid protein (GFAP) in microglia-enriched or astrocyte-enriched cultures. The expression of iNOS and the production of NO in microglia-enriched cultures were significantly higher than those in the identically stimulated astrocyte-enriched cultures. These results demonstrate that PTKs are involved in the signaling events of LPS-induced NO production in microglia and astrocytes, and that microglia are more responsive than astrocytes to stimuli which induce NO. These results may provide insights into therapeutic interventions in the pathway for NO production in the brain.

Authors+Show Affiliations

Section of Neuropharmacology, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC 27709, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8874881

Citation

Kong, L Y., et al. "Protein Tyrosine Kinase Inhibitors Suppress the Production of Nitric Oxide in Mixed Glia, Microglia-enriched or Astrocyte-enriched Cultures." Brain Research, vol. 729, no. 1, 1996, pp. 102-9.
Kong LY, McMillian MK, Maronpot R, et al. Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures. Brain Res. 1996;729(1):102-9.
Kong, L. Y., McMillian, M. K., Maronpot, R., & Hong, J. S. (1996). Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures. Brain Research, 729(1), 102-9.
Kong LY, et al. Protein Tyrosine Kinase Inhibitors Suppress the Production of Nitric Oxide in Mixed Glia, Microglia-enriched or Astrocyte-enriched Cultures. Brain Res. 1996 Aug 5;729(1):102-9. PubMed PMID: 8874881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protein tyrosine kinase inhibitors suppress the production of nitric oxide in mixed glia, microglia-enriched or astrocyte-enriched cultures. AU - Kong,L Y, AU - McMillian,M K, AU - Maronpot,R, AU - Hong,J S, PY - 1996/8/5/pubmed PY - 1996/8/5/medline PY - 1996/8/5/entrez SP - 102 EP - 9 JF - Brain research JO - Brain Res VL - 729 IS - 1 N2 - Nitric oxide (NO) produced by glial cells has been implicated in the neuropathogenesis of various diseases. However, the signaling transduction pathway(s) for the production of NO in these cells is not well understood. To test whether protein tyrosine kinases (PTKs) are required for signaling events of NO production in glial cells, this study examined the effects of genistein and tyrphostin A25, two potent inhibitors of PTKs, on the production of NO in mouse primary mixed glia, microglia-enriched or astrocyte-enriched cultures exposed to lipopolysaccharide (LPS) or a combination of LPS and interferon-gamma (IFN gamma). LPS induced a dose-dependent increase in NO production from the mixed glia cultures. The LPS-induced NO production was significantly enhanced by stimulating the cells with IFN gamma. Genistein or tyrphostin A25 inhibited the production of NO in both LPS- and IFN gamma/LPS-stimulated mixed glia cultures. The production of NO in the stimulated microglia-enriched or astrocyte-enriched cultures was also inhibited by tyrphostin A25. To verify the cellular sources of NO, immunocytochemical staining of inducible NO synthase (iNOS) was followed by staining with the microglia marker Mac-1 or the astrocyte marker glial fibrillary acid protein (GFAP) in microglia-enriched or astrocyte-enriched cultures. The expression of iNOS and the production of NO in microglia-enriched cultures were significantly higher than those in the identically stimulated astrocyte-enriched cultures. These results demonstrate that PTKs are involved in the signaling events of LPS-induced NO production in microglia and astrocytes, and that microglia are more responsive than astrocytes to stimuli which induce NO. These results may provide insights into therapeutic interventions in the pathway for NO production in the brain. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/8874881/Protein_tyrosine_kinase_inhibitors_suppress_the_production_of_nitric_oxide_in_mixed_glia_microglia_enriched_or_astrocyte_enriched_cultures_ L2 - https://linkinghub.elsevier.com/retrieve/pii/0006-8993(96)00417-9 DB - PRIME DP - Unbound Medicine ER -