GLUTATHIONE DEFICIENCY INCREASES HEPATIC ASCORBIC-ACID SYNTHESIS IN ADULT MICE
GLUTATHIONE DEFICIENCY INCREASES HEPATIC ASCORBIC-ACID SYNTHESIS IN ADULT MICE
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DOI：
10.1073/pnas.89.23.11566
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发表时间：
1992-12-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
--
作者：
MARTENSSON, J;MEISTER, A
在成年小鼠中，通过给予丁硫氨酸亚砜亚胺（谷胱甘肽合成的抑制剂）诱导的谷胱甘肽缺乏症导致肝脏中抗坏血酸盐的快速和大幅增加。这种效果在给予抑制剂后2-4小时明显;随后，抗坏血酸盐的水平降低，脱氢抗坏血酸盐的水平显著增加，支持谷胱甘肽在生理上起作用以保持抗坏血酸盐处于其还原形式的结论。在肾脏和肺也，抗坏血酸水平下降，脱氢抗坏血酸增加。谷胱甘肽缺乏的成年小鼠抗坏血酸合成增加似乎可以保护组织免受损伤。相比之下，新生大鼠（像豚鼠和人类）显然不能合成抗坏血酸，肝脏和其他器官受到严重损害;以前的研究表明，抗坏血酸的管理可以防止这种组织损伤。研究结果支持这样的观点，即谷胱甘肽和抗坏血酸的抗氧化作用是密切相关的，并涉及一种机制，其中谷胱甘肽水平的降低，可能与氧化事件，刺激抗坏血酸的合成。
Glutathione deficiency, induced in adult mice by administering buthionine sulfoximine (an inhibitor of glutathione synthesis), led to a rapid and substantial increase in ascorbate in the liver. This effect was apparent 2-4 hr after giving the inhibitor; subsequently, the level of ascorbate decreased and that of dehydroascorbate increased markedly, supporting the conclusion that glutathione functions physiologically to keep ascorbate in its reduced form. In kidney and lung also, ascorbate levels decreased, and dehydroascorbate increased. Increased synthesis of ascorbate in glutathione-deficient adult mice seems to protect against tissue damage. In contrast, newborn rats, which (like guinea pigs and humans) apparently do not synthesize ascorbate, suffer severe damage to liver and other organs; previous studies showed that administration of ascorbate prevents such tissue damage. The findings support the view that the antioxidant actions of glutathione and ascorbate are closely linked and involve a mechanism in which decrease of the glutathione level, perhaps associated with an oxidative event, stimulates ascorbate synthesis.