US EPA

1797846 

Journal Article 

Role of HO-1 in the Arsenite-Induced Neurotoxicity in Primary Cultured Cortical Neurons 

Teng, YC; Tai, YI; Lee, YH; Lin, AM 

2013 

1 

Molecular Neurobiology
ISSN: 0893-7648 

48 

2 

281-287 

English 

23824679 

10.1007/s12035-013-8492-9 

WOS:000324640600003 

In the present study, the role of heme oxygenase (HO)-1 in sodium arsenite (arsenite)-induced neurotoxicity was investigated using primary cultured cortical neurons. Incubation with arsenite was found to cause cell death of primary cultured cortical neurons in concentration- and time-dependent manners. Furthermore, arsenite induced caspase 3 activation and decreased procaspase 12 levels, indicating that apoptosis is involved in the arsenite-induced neurotoxicity. The oxidative mechanism underlying arsenite-induced neurotoxicity was investigated. Western blot assay showed that arsenite significantly increased HO-1 levels, a redox-regulated protein. Co-incubation with glutathione (10 mM) attenuated arsenite-induced HO-1 elevation and caspase 3 activation, suggesting that oxidative stress is involved in the arsenite-induced neurotoxicity. The neurotoxic effects of inorganic arsenics were compared; arsenite was more potent than arsenate in inducing HO-1 expression and caspase 3 activation. Moreover, the cell viabilities of arsenite and arsenate were 60 ± 2 and 99 ± 2 % of control, respectively. HO-1 siRNA transfection was employed to prevent arsenite-induced HO-1 elevation. At the same time, arsenite-induced caspase 3 activation and neuronal death were attenuated in the HO-1 siRNA-transfected cells. Taken together, HO-1 appears to be neuroprotective in the arsenite-induced neurotoxicity in primary cultured cortical neurons. In addition to antioxidants, HO-1 elevation may be a neuroprotective strategy for arsenite-induced neurotoxicity. 

Arsenite; Neurotoxicity; HO-1; Oxidative stress