Related Experiment Videos
P38 MAPK, but not p42/p44 MAPK mediated inducible nitric oxide synthase expression in C6 glioma cells
1Department of Pharmaceutical Sciences, College of Pharmacy, Nova Southeastern University, Fort Lauderdale, FL 33328, USA.
Abstract:
Recently mitogen-activated protein kinase (MAPK) has been reported to play an important role in phosphorylation cascades governing cell growth and protein expression in numerous cell types. In order to explore the signaling mechanism by which inducible nitric oxide synthase (iNOS) is regulated in C6 glioma cells, we investigated the role of MAPK in iNOS expression by using the specific MAPK inhibitors. First the induction of nitric oxide by lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), alone or their combination, was studied in C6 glioma cells. Administration of LPS, TNFalpha, or IFNgamma alone had no detectable stimulatory effect on the production of nitric oxide (NO). However, combination of the three factors elicited a significant elevation of NO level in C6 cell culture medium. Subsequently pretreatment of C6 cells with a specific inhibitor of p38 MAPK, SB202190, resulted in a dose-dependent inhibition of NO production and iNOS expression, but PD98059, an inhibitor of p42/p44 MAPK activation, had no effect. These data suggest that p38 MAPK mediates iNOS expression in C6 glioma cells, but p42/p44 MAPK is not involved in this process.
Insights
Mitogen-activated protein kinase (MAPK) regulates inducible nitric oxide synthase (iNOS) in C6 glioma cells. The p38 MAPK pathway, not p42/p44 MAPK, is crucial for iNOS expression.
Area of Science:
- Cellular signaling pathways
- Neuroscience
- Biochemistry
Background:
- Mitogen-activated protein kinase (MAPK) is involved in cell growth and protein expression.
- Inducible nitric oxide synthase (iNOS) plays a role in various cellular processes.
- Understanding iNOS regulation in C6 glioma cells is important for neurological research.
Purpose of the Study:
- To investigate the role of MAPK in regulating iNOS expression in C6 glioma cells.
- To determine which specific MAPK pathways are involved in iNOS induction.
Main Methods:
- C6 glioma cells were treated with lipopolysaccharide (LPS), tumor necrosis factor alpha (TNFalpha), and interferon gamma (IFNgamma).
- Nitric oxide (NO) production and iNOS expression were measured.
- Specific MAPK inhibitors, SB202190 (p38 MAPK inhibitor) and PD98059 (p42/p44 MAPK inhibitor), were used.
Main Results:
- Combined treatment with LPS, TNFalpha, and IFNgamma significantly increased NO production.
- SB202190 dose-dependently inhibited NO production and iNOS expression.
- PD98059 had no effect on NO production or iNOS expression.
Conclusions:
- p38 MAPK mediates iNOS expression in C6 glioma cells.
- p42/p44 MAPK is not involved in the regulation of iNOS in this cell model.
- These findings elucidate a specific signaling pathway for iNOS regulation in glioma cells.