Arsenite-induced cytotoxicity in dorsal root ganglion explants

doi:10.1016/j.freeradbiomed.2007.12.014

Chia Nan University of Pharmacy & Science Institutional Repository > 環境永續暨休閒學院 > 休閒保健管理系(所) > 期刊論文 > Item 310902800/21588

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標題:	Arsenite-induced cytotoxicity in dorsal root ganglion explants
作者:	Y. H. Chou P. L. Chao M. J. Tsai H. H. Cheng K. B. Chen D. M. Yang C. H. Yang A. M. Y. Lin 陳昆伯
貢獻者:	休閒保健管理系
關鍵字:	Arsenic DRG explants Apoptosis Mitochondria ER stress GDNF
日期:	2008-04
上傳時間:	2009-07-23 10:28:38 (UTC+8)
摘要:	Peripheral neuropathy is common in people chronically overexposed to arsenic. We studied sodium arsenite (arsenite)-induced cytotoxicity in dorsal root ganglion (DRG) explants. Incubation with arsenite concentration- and time-dependently increased the expression of stress proteins, heat shock protein 70, and heme oxygenase-1 in DRG explants. Furthermore, apoptosis was involved in the arsenite-induced cytotoxicity in the treated DRG. Elevation in cytosolic cytochrome c levels and reduction in procaspase 3 levels suggested an involvement of the mitochondrial pathway in arsenite-induced apoptosis in this preparation. At the same time, increases in the activating transcription factor-4 and C/EBP homologous protein and reduction in procaspase 12 levels indicated activation of the endoplasmic reticulum (ER) pathway in the arsenite-induced cytotoxicity in DRG explants. Salubrinal (30 μM), an ER inhibitor, was found to attenuate arsenite-induced DNA fragmentation and reduction in procaspase 12 in DRG explants. Cytotoxic effects by arsenite, sodium arsenate (arsenate), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were compared, and the potency was as follows: arsenite >>> arsenate > MMA and DMA. Recombinant adenovirus vectors encoding glial-cell-derived neurotrophic factor (AdGDNF) genes allowed a stable delivery of GDNF genes to the infected cells in DRG explants. Applied in this manner, AdGDNF was found to inhibit arsenite-induced DNA fragmentation in DRG explants. Moreover, AdGDNF attenuated the arsenite-induced reduction in procaspases 3 and 12 levels. Taken together, our study demonstrates that arsenite is capable of inducing cytotoxicity in DRG explants. Both ER and mitochondria pathways are involved in the arsenite-induced apoptosis in DRG explants. Glial-cell-derived neurotrophic factor appears to be protective against arsenite-induced peripheral neuropathy.
關聯:	Free radical biology & medicine 44(8)：p.1553-1561
显示于类别:	[休閒保健管理系(所)] 期刊論文

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