Cheng Ya-Hsin, Ou Bor-Rung, Cheng Li-Chuan, Lu Jian-He, Yeh Jan-Ying
Division of Environmental Health and Occupational Medicine, National Health Research Institutes, Zhunan, Miaoli 305, Taiwan, ROC.
Toxicol In Vitro. 2008 Dec;22(8):1832-9. doi: 10.1016/j.tiv.2008.08.006. Epub 2008 Sep 2.
The objective was to investigate the regulation of glutathione (GSH) turnover in porcine aortic endothelial cells (PAECs) treated with sodium arsenite (NaAsO(2)), arsenic trioxide (As(2)O(3)) or sodium arsenate (Na(2)HAsO(4)) up to 72 hr at 0, 1, 5, and 10 microM, respectively. Intracellular GSH and glutathione disulfide (GSSG) contents, as well as the activities and mRNA levels of glutamate-cysteine lyase (GCL; gamma-glutamylcysteine synthetase) and gamma-glutamyl transpeptidase (GGT), were examined. The trivalent arsenic compounds increased GSH and GSSG contents in PAECs. An increase in GCL activity was observed at 24hr whereas an increase in GCL mRNA level was observed at 72 hr. The increase in GGT activity was only observed at 72 hr. In addition, a tendency of increase in GGT mRNA level was observed. Na(2)HAsO(4) treatment did not affect GSH content and the turnover-related enzymes. A differential GSH modulation in PAECs by trivalent arsenic compounds was found. The regulatory mechanism responsible for the As(2)O(3)-induced GSH increase is related to the GSH-turnover enzymes, GCL and GGT, while that for the NaAsO(2)-induced GSH increase may not be related to expression of GSH-turnover enzymes.
目的是研究分别用0、1、5和10微摩尔的亚砷酸钠（NaAsO₂）、三氧化二砷（As₂O₃）或砷酸钠（Na₂HAsO₄）处理猪主动脉内皮细胞（PAECs）长达72小时后谷胱甘肽（GSH）周转的调节情况。检测了细胞内GSH和谷胱甘肽二硫化物（GSSG）的含量，以及谷氨酸 - 半胱氨酸裂合酶（GCL；γ-谷氨酰半胱氨酸合成酶）和γ-谷氨酰转肽酶（GGT）的活性和mRNA水平。三价砷化合物增加了PAECs中GSH和GSSG的含量。在24小时时观察到GCL活性增加，而在72小时时观察到GCL mRNA水平增加。仅在72小时时观察到GGT活性增加。此外，还观察到GGT mRNA水平有增加的趋势。Na₂HAsO₄处理不影响GSH含量和与周转相关的酶。发现三价砷化合物对PAECs中的GSH有不同的调节作用。As₂O₃诱导的GSH增加的调节机制与GSH周转酶GCL和GGT有关，而NaAsO₂诱导的GSH增加的调节机制可能与GSH周转酶的表达无关。
