Effects of glutathione reductase inhibition on cellular thiol redox state and related systems.

Effects of glutathione reductase inhibition on cellular thiol redox state and related systems.
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DOI:
10.1016/j.abb.2009.03.001
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发表时间:
2009-05-01
影响因子:
3.9
通讯作者:
Guan X
Guan X
中科院分区:
生物学3区
文献类型:
--
作者:
Zhao Y;Seefeldt T;Chen W;Wang X;Matthees D;Hu Y;Guan X

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虽然谷胱甘肽还原酶(GR)的抑制已被证明会导致还原型谷胱甘肽(GSH)的减少和谷胱甘肽二硫化物(GSSG)的增加,但尚未注意到GR抑制对巯基氧化还原状态和相关系统的影响的系统研究。以猴肾细胞为模型,以2-乙酰氨基-3-[4-(2-乙酰氨基-2-羧基乙硫基-羰基氨基)苯硫氨甲酰基硫基]丙酸(2-AAPA)为GR抑制剂,研究GR抑制对细胞巯基氧化还原状态及相关系统的影响。我们的研究表明,除了GSH减少和GSSG增加外,2-AAPA还增加了NADH/NAD+和NADPH/NADP+的比值。观察到显著的蛋白谷胱甘肽化。然而,这种抑制并不影响活性氧的形成或抗氧化防御酶系统[GR、谷胱甘肽过氧化物酶、过氧化氢酶和超氧化物歧化酶]和参与GSH生物合成的酶[γ-谷氨酰半胱氨酸合成酶和谷胱甘肽合成酶]的表达。
Although inhibition of glutathione reductase (GR) has been demonstrated to cause a decrease in reduced glutathione (GSH) and increase in glutathione disulfide (GSSG), a systematic study of the effects of GR inhibition on thiol redox state and related systems has not been noted. By employing a monkey kidney cell line as the cell model and 2-acetylamino-3-[4-(2-acetylamino-2-carboxy-ethylsulfanylthio-carbonylamino)phenylthiocarbamoylsulfanyl]propionic acid (2-AAPA) as a GR inhibitor, an investigation of the effects of GR inhibition on cellular thiol redox state and related systems was conducted. Our study demonstrated that, in addition to a decrease in GSH and increase in GSSG, 2-AAPA increased the ratios of NADH/NAD+ and NADPH/NADP+. Significant protein glutathionylation was observed. However, the inhibition did not affect the formation of reactive oxygen species or expression of antioxidant defense enzyme systems [GR, glutathione peroxidase, catalase, and superoxide dismutase)] and enzymes involved in GSH biosynthesis [γ-glutamylcysteine synthetase and glutathione synthetase].
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