Neuroprotective effect of adenoviral catalase gene transfer in cortical neuronal cultures

Abstract

Reduced availability of reactive oxygen species is a key component of neuroprotection against toxic stimuli. Recently, we have shown that the hydrogen peroxide scavenger catalase plays a central role in delayed preconditioning induced by the mitochondrial ATP‐sensitive potassium channel opener BMS‐191095 (Gáspár et al. JCBFM 28 (6): 1090‐1103, 2008). The aim of our present experiments was to investigate the neuroprotective effect of catalase in vitro using an adenoviral catalase gene transfer protocol. To induce catalase overexpression, cultured rat cortical neurons were incubated with the adenoviral vector Ad5CMVcatalase and control cells with Ad5CMVntLacZ for 24 h. Gene transfer increased catalase protein levels and activity, but did not influence other antioxidants. Catalase transfection did not protect against glutamate excitotoxicity and oxygen‐glucose deprivation, but conferred a dose‐dependent neuroprotection against 6 h exposure to 80 μM hydrogen peroxide (viability: control, 20.70±1.96%; LacZ 10 pfu/cell, 15.00± 1.66%; catalase 1 pfu/cell, 57.60±5.46%*; catalase 2 pfu/cell, 104.90±1.74%*; catalase 10 pfu/cell, 111.20±1.92%*; *p<0.05 vs. control; mean±SEM). Finally, the protection could be antagonized using the catalase inhibitor 3‐aminotriazole. Our results support the view that enhancing cellular antioxidant capacity may play a crucial role in neuroprotective strategies.