Neuroglobin involvement in the course of arsenic toxicity in rat cerebellar granule neurons.
Exposure to arsenic in drinking water results in a widespread environmental problem in the world, and the brain is a major target. Neuroglobin is a vertebrate heme protein regarded as playing neuroprotective role in hypoxia or oxidative stress. In this study, we investigated the toxic effects of sodium arsenite (NaAsO2) on primary cultured rat cerebellar granule neurons (CGNs) and detected neuroglobin (Ngb) expression in rat CGNs exposed to NaAsO2. Our results show that apoptosis was obviously induced by NaAsO2 treatment in rat CGNs by annexin V-fluorescein isothiocyanate assay. Intracellular reactive oxygen species generation increased significantly in the cells exposed to NaAsO2, and the apoptotic effects could be partially reversed by antioxidant N-acetyl-L-cysteine. Ngb protein and mRNA expression were significantly downregulated in rat CGNs shortly after NaAsO2 exposure and then upregulated after a longer time of exposure. Furthermore, mRNA expression changed more than protein expression and the toxic effect of NaAsO2 on Ngb expression is dose dependent. Higher Ngb expression was also detected in rat cerebellum, but not in other parts (cerebrum, hippocampus, and midbrain) of the brain exposed to NaAsO2 for 16 weeks. Taken together, cytotoxic effects of NaAsO2 on rat CGNs is induced at least partly by oxidative stress and Ngb may influence the course of arsenic toxicity in rat CGNs and rat cerebellum.
Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Key Lab of Etiology and Epidemiology, Education Bureau of Heilongjiang Province & Ministry of Health (23618104), Harbin Medical University, 157# Baojian Road, Harbin, 150081, People's Republic of China.
Xiaona
X
Liu
Yanhui
Y
Gao
Hongju
H
Yao
Lingwang
L
Zhou
Dianjun
D
Sun
Jing
J
Wang
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002531:Cerebellum / Q000166:cytology*; D005914:Globins / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000078787:Neuroglobin; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins; D001151:Arsenic