Down‐regulation of apurinic/apyrimidinic endonuclease 1 (APE1) in spinal motor neurones under oxidative stress

Aim Apurinic/apyrimidinic endonuclease 1 ( APE 1) is an intermediate enzyme in base excision repair which is important for removing damaged nucleotides under normal and pathological conditions. Accumulation of damaged bases causes genome instability and jeopardizes cell survival. Our study is to examine APE 1 regulation under oxidative stress in spinal motor neurones which are vulnerable to oxidative insult. Methods We challenged the motor neurone‐like cell line NSC ‐34 with hydrogen peroxide and delineated APE 1 function by applying various inhibitors. We also examined the expression of APE 1 in spinal motor neurones after spinal root avulsion in adult rats. Results We showed that hydrogen peroxide induced APE 1 down‐regulation and cell death in a differentiated motor neurone‐like cell line. Inhibiting the two functional domains of APE 1, namely, DNA repair and redox domains potentiated hydrogen peroxide induced cell death. We further showed that p53 phosphorylation early after hydrogen peroxide treatment might contribute to the down‐regulation of APE 1. Our in vivo results similarly showed that APE 1 was down‐regulated after root avulsion injury in spinal motor neurones. Delay of motor neurone death suggested that APE 1 might not cause immediate cell death but render motor neurones vulnerable to further oxidative insults. Conclusion We conclude that spinal motor neurones down‐regulate APE 1 upon oxidative stress. This property renders motor neurones susceptible to continuous challenge of oxidative stress in pathological conditions.