Repulsive guidance molecule a suppresses seizures and mossy fiber sprouting via the FAK‑p120RasGAP‑Ras signaling pathway.

Publisher: D. A. Spandidos Country of Publication: Greece NLM ID: 101475259 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1791-3004 (Electronic) Linking ISSN: 17912997 NLM ISO Abbreviation: Mol Med Rep

Original Publication: Athens, Greece : D. A. Spandidos

Signal Transduction*/drug effects; Focal Adhesion Protein-Tyrosine Kinases/*metabolism ; Membrane Glycoproteins/*metabolism ; Mossy Fibers, Hippocampal/*metabolism ; Nerve Tissue Proteins/*metabolism ; Seizures/*metabolism ; Seizures/*physiopathology ; p120 GTPase Activating Protein/*metabolism ; ras Proteins/*metabolism; Animals ; Disease Models, Animal ; GPI-Linked Proteins ; Gene Expression ; Male ; Membrane Glycoproteins/administration & dosage ; Mossy Fibers, Hippocampal/physiopathology ; Nerve Tissue Proteins/administration & dosage ; Pentylenetetrazole/adverse effects ; Phosphorylation ; Protein Binding ; Rats ; Recombinant Proteins ; Seizures/drug therapy ; Seizures/etiology ; ras Proteins/genetics

Repulsive guidance molecule a (RGMa) is a membrane‑associated glycoprotein that regulates axonal guidance and inhibits axon outgrowth. In our previous study, we hypothesized that RGMa may be involved in temporal lobe epilepsy (TLE) via the repulsive guidance molecule a (RGMa)‑focal adhesion kinase (FAK)‑Ras signaling pathway. To investigate the role of RGMa in epilepsy, recombinant RGMa protein and FAK inhibitor 14 was intracerebroventricularly injected into a pentylenetetrazol (PTZ) kindling model and Timm staining, co‑immunoprecipitation and western blotting analyses were subsequently performed. The results of the present study revealed that intracerebroventricular injection of recombinant RGMa protein reduced the phosphorylation of FAK (Tyr397) and intracerebroventricular injection of FAK inhibitor 14 reduced the interaction between FAK and p120GAP, as wells as Ras expression. Recombinant RGMa protein and FAK inhibitor 14 exerted seizure‑suppressant effects; however, recombinant RGMa protein but not FAK inhibitor 14 suppressed mossy fiber sprouting in the PTZ kindling model. Collectively, these results demonstrated that RGMa may be considered as a potential therapeutic agent for epilepsy, and that RGMa may exert the aforementioned biological effects partly via the FAK‑p120GAP‑Ras signaling pathway.

0 (GPI-Linked Proteins)
0 (Membrane Glycoproteins)
0 (Nerve Tissue Proteins)
0 (RGM protein, rat)
0 (Recombinant Proteins)
0 (p120 GTPase Activating Protein)
EC 2.7.10.2 (Focal Adhesion Protein-Tyrosine Kinases)
EC 3.6.5.2 (ras Proteins)
WM5Z385K7T (Pentylenetetrazole)

Date Created: 20190301 Date Completed: 20190730 Latest Revision: 20191210

20240829

10.3892/mmr.2019.9951

30816469