Ape1 protects against MPP+-induced neurotoxicity through ERK1/2 signaling in PC12 cells. Issue 1 (1st January 2017)

• Record Type: Journal Article
• Authors: Kang, Bei; Mu, Shengzhi; Yang, Qian; Guo, Shenglong; Chen, Xiaoli; Guo, Hena
• Is Part Of: NeuroReport. Volume 28:Issue 1(2017)
• Publication Date: 2017-01-01
• Subjects: Ape1 -- apoptosis -- oxidative stress -- Parkinson's disease -- PC12 cell; Neurosciences -- Periodicals; Nervous system -- Periodicals; Neurophysiology -- Periodicals; Nervous System Diseases -- Periodicals; Nervous System Physiological Phenomena -- Periodicals; Neurosciences -- Periodicals; 616.805
• DOI: 10.1097/WNR.0000000000000712
• Languages: English
• ISSNs: 0959-4965

Abstract

Abstract : Oxidative stress, induced by reactive oxygen species (ROS), is an apoptosis activator. Oxidative stress causes dopaminergic neuron loss and plays a pivotal role in the pathogenesis of Parkinson's disease (PD). A recent study showed that apurinic/apyrimidinic endonuclease 1 (Ape1) decreases cytotoxicity and promotes neuron survival under oxidative stress. Furthermore, it has been proven that Ape1 is involved in the pathogenesis of PD. However, little is known about the contribution of Ape1 toward the development of PD. Thus, the present study was designed to define a critical pathway by which Ape1 mediates neurotoxicity in a model of PD. The results show that Ape1 was upregulated in MPP + -treated PC12 cells. Ape1 overexpression significantly increased cell viability and inhibited apoptosis compared with MPP + treatment, whereas Ape1 knockdown showed the opposite effect. Ape1 overexpression markedly suppressed ROS levels, whereas Ape1 knockdown significantly elevated ROS levels. Furthermore, Ape1 overexpression markedly upregulated the p-ERK1/2 protein expression level and inhibited ERK1/2 signaling. The ERK1/2 inhibitor PD98059 significantly decreased cell viability and increased apoptosis and the ROS level compared with the Ape1 overexpression group. Taken together, these results suggest that Ape1 protects against neuron death by activating the ERK1/2 signaling pathway.