Identification of VEGF signaling pathways involved in neuroprotection against G93A-SOD1
TUNEL labeling to identify signaling pathways responsible for VEGF neuroprotection against G93A-SOD1-induced DNA fragmentation. Treatment with AdmSOD (1000 ng/ml) results in DNA damage and is significantly attenuated by VEGF treatment (250 ng/ml). Inhibition of VEGFR2 signaling with SU1498 (20µM; 1 h pretreatment) prevents VEGF neuroprotection. Inhibition of PI3K/Akt signaling with LY294002 (20µM; 1 h pretreatment) also prevents VEGF neuroprotection, while inhibition of p44/42 MAPK signaling with U0126 (20µM; 1 h pretreatment) has no effect on VEGF neuroprotection. Results are averaged over at least 10 fields of 3 independent experiments and analyzed for statistical significance using one-way ANOVA followed by Tukey’s multiple comparison test (*P < 0.01 compared to mSOD + VEGF).