Related Experiment Video
Updated: Jun 9, 2025
Quantitative Immunohistochemistry of the Cellular Microenvironment in Patient Glioblastoma Resections
Published on: July 31, 2017
Role of Glutamine Synthetase on Vascular Permeability in Gliomas
Dandan Wang1,2, Tianwei Song2, Zongtao Hu2
1School of Basic Medical Sciences, Anhui Medical University, Hefei, P.R. China.
Background/Aim:
This study aimed to investigate the effect and underlying mechanism of inhibiting glutamine synthetase (GS) on the vascular permeability of gliomas.
Materials And Methods:
C6 glioma rat models were randomly divided into control and L-methionine sulfoximine (MSO) treatment groups. MSO was intraperitoneally injected once every other day for a total of three injections in the MSO group. We assessed the effect of MSO on tumor vascular permeability by tail vein injection of Evans blue dye. GS activity, glutamate (Glu) concentration, glutamine (Gln) concentration, and arginine concentration in tumor tissues were measured using the corresponding kits. qPCR experiments were then conducted to examine the effect of glutamate concentration on N-methyl-D-aspartate (NMDA) receptor expression. Finally, the nitric oxide synthase (NOS) assay kit and the nitric oxide (NO) assay kit were employed to detect NOS activity and NO concentration changes, respectively.
Results:
Increased glioma tumor vascular permeability was observed after intraperitoneal injection of MSO; MSO acted as an inhibitor of GS, leading to a decrease in GS activity; increased glutamate levels caused activation of NMDA receptors and further activation of NOS; additionally, elevated NO levels were detected in association with an increase in arginine and NOS.
Conclusion:
Inhibiting GS results in increased vascular permeability in gliomas, which is associated with elevated NO levels and the vasodilatory effects of NO.
Insights
Inhibiting glutamine synthetase (GS) increases glioma vascular permeability. This is linked to higher nitric oxide (NO) levels, driven by glutamate and N-methyl-D-aspartate receptor activation.
Area of Science:
- Neuro-oncology
- Vascular Biology
- Biochemistry
Background:
- Gliomas exhibit abnormal vascular permeability, impacting treatment efficacy.
- Glutamine synthetase (GS) plays a role in brain amino acid metabolism.
- Understanding GS inhibition's effect on glioma vasculature is crucial.
Purpose of the Study:
- To investigate how inhibiting glutamine synthetase (GS) affects glioma vascular permeability.
- To elucidate the underlying molecular mechanisms, including the role of nitric oxide (NO).
Main Methods:
- C6 glioma rat models were treated with L-methionine sulfoximine (MSO), a GS inhibitor.
- Vascular permeability was assessed using Evans blue dye.
- GS activity, glutamate, glutamine, and arginine levels were quantified.
- NMDA receptor expression, NOS activity, and NO levels were measured.
Main Results:
- MSO treatment inhibited GS activity and increased glioma vascular permeability.
- Elevated glutamate levels led to NMDA receptor and NOS activation.
- Increased arginine levels correlated with elevated nitric oxide (NO) production.
Conclusions:
- Inhibiting GS increases glioma vascular permeability.
- This effect is mediated by elevated NO levels, resulting from glutamate accumulation and subsequent NMDA receptor and NOS activation.
More Related Videos
07:39Co-culture of Glutamatergic Neurons and Pediatric High-Grade Glioma Cells Into Microfluidic Devices to Assess Electrical Interactions
Published on: November 17, 2021
10:08Co-culture of Glioblastoma Stem-like Cells on Patterned Neurons to Study Migration and Cellular Interactions
Published on: February 24, 2021
