Role of NADPH oxidase in brain damage oxidative stress in ATP7Btx-J mice / 中华神经医学杂志

ABSTRACT

Objective To investigate whether NADPH oxidase is involved in brain damage of ATP7Btx-J mice through interfering oxidative stress.Methods ATP7Btx-J mice (20 weeks old),wild-type (WT) mice (20 weeks old) and apo-ATP7Btx-J mice (given the NADPH oxidase inhibitor apocynin) were chosen in our study; apo-ATP7Btx-J mice were treated by daily oral administration with 200 mg/kg of apocynin since 16 weeks old till 20 weeks old.Copper concentration was determined by inductively coupled plasma-mass spectrometry (ICP-MS) and NADPH oxidase activity was detected by colorimetric method.The superoxide level was measured using superoxide-sensitive fluorescent probe dihyroethidine (DHE).The protein expression level of Cleaved caspase-3 was analyzed by Western blotting.The level of neuronal apoptosis was assayed with TUNEL method.Results The copper content in the striatum region of ATP7Btx-J mice was significantly higher than that of wild-type (WT) mice (P＜0.05).The activity ofNADPH oxidase and concentration of superoxide anion in the striatum region of ATP7Btx-J mice were significantly higher than those of WT mice (P＜0.05); those in the striatum region of apo-ATP7Btx-J mice were significantly lower than those of ATP7Btx-J mice (P＜0.05).The protein expression of Cleaved caspase-3 and the level of neuronal apoptosis in the striatum region of ATP7Btx-J mice were significantly higher than those of WT mice (P＜0.05); those in the striatum region of apoATP7Btx-J mice were significantly lower than that of ATP7Btx-J mice (P＜0.05).Conclusion NADPH oxidase may play a role in neuronal apoptosis in the striatum region of ATP7Btx-J mice through oxidative stress,and apocynin can protect the nervous system decreasing the NADPH oxidase level.