Colistin-Induced Apoptosis of Neuroblastoma-2a Cells Involves the Generation of Reactive Oxygen Species, Mitochondrial Dysfunction, and Autophagy

Molecular Neurobiology
Chongshan DaiXilong Xiao

Abstract

Neurotoxicity remains a poorly characterized adverse effect associated with colistin therapy. The aim of the present study was to investigate the mechanism of colistin-induced neurotoxicity using the mouse neuroblastoma2a (N2a) cell line. Colistin treatment (0-200 μM) of N2a neuronal cells induced apoptotic cell death in a dose-dependent manner. Colistin-induced neurotoxicity was associated with a significant increase of reactive oxygen species (ROS) levels, with a concomitant decrease in the activities of superoxide dismutase (SOD), catalase (CAT), and the glutathione (GSH) levels. Mitochondrial dysfunction was evident from the dissipation of membrane potential and the increase of Bax/Bcl-2, followed by the release of cytochrome c (CytC). Caspase-3/7, -8, and -9 activations were also detected. Colistin-induced neurotoxicity significantly increased the gene expression of p53 (1.6-fold), Bax (3.3-fold), and caspase-8 (2.2-fold) (all p < 0.01). The formation of autophagic vacuoles was evident with the significant increases (all p < 0.05 or 0.01) of both of Beclin 1 and LC3B following colistin treatment (50-200 μM). Furthermore, inhibition of autophagy by pretreatment with chloroquine diphosphate (CQ) enhanced colistin-induced apo...Continue Reading

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Citations

Mar 29, 2016·Neurotoxicology and Teratology·Jian WangJichang Li
May 3, 2016·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Chao ZhangYing-Feng Zhou
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Jan 19, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Daowen LiShusheng Tang
Jan 20, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Xinyan PengJingru Qiu
Nov 16, 2019·Animal Science Journal = Nihon Chikusan Gakkaihō·Qian LinQiuzhong Dai
Oct 2, 2019·Archives of Toxicology·Chongshan DaiTony Velkov
Jan 26, 2021·Frontiers in Veterinary Science·Xinyan PengSubhajit Das Gupta
Feb 26, 2021·Pharmacological Reviews·Sue C NangJian Li
May 21, 2021·Expert Review of Clinical Pharmacology·Fatemeh Jafari, Sepideh Elyasi
Feb 11, 2020·ACS Infectious Diseases·Chongshan DaiShusheng Tang
May 19, 2020·ACS Infectious Diseases·Chongshan DaiXilong Xiao

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