GLUTATHIONE DEFICIENCY LEADS TO MITOCHONDRIAL DAMAGE IN BRAIN
GLUTATHIONE DEFICIENCY LEADS TO MITOCHONDRIAL DAMAGE IN BRAIN
复制标题
DOI：
10.1073/pnas.88.5.1913
复制
发表时间：
1991-03-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
--
作者：
JAIN, A;MARTENSSON, J;MEISTER, A
谷氨酰半胱氨酸合成酶的选择性抑制剂丁硫酰亚砜亚胺（buthiflavine sulfoximine）可使新生大鼠大脑皮层谷胱甘肽水平明显降低，线粒体明显增大和变性。 这些作用被谷胱甘肽单乙酯阻止，这缓解了谷胱甘肽的缺乏，但这样的效果并没有被谷胱甘肽阻止，这表明谷胱甘肽是不是由大脑皮层明显采取。 众所周知，线粒体使用的一些氧气会转化为过氧化氢。 我们认为，在谷胱甘肽缺乏症，过氧化氢积累和损害线粒体。 因此，在正常生理条件下，谷氨酸在线粒体中具有重要功能。 对新生大鼠、断奶前大鼠和成年大鼠脑谷胱甘肽周转和利用的观察表明：（1）某些谷胱甘肽周转迅速，（t1/2，成人几乎等于30分钟，新生儿几乎等于8分钟），（ii）可能存在几个谷胱甘肽池，和（iii）脑利用血浆谷胱甘肽，可能通过γ-谷氨酰转肽酶启动的途径，但不是全部;因此，存在半胱氨酸部分的回收或转运。 这些研究为涉及谷胱甘肽缺乏的人类疾病提供了动物模型，并与新生儿中发生的氧化现象有关。
Glutathione deficiency induced in newborn rats by giving buthionine sulfoximine, a selective inhibitor of gamma-glutamylcysteine synthetase, led to markedly decreased cerebral cortex glutathione levels and striking enlargement and degeneration of the mitochondria. These effects were prevented by giving glutathione monoethyl ester, which relieved the glutathione deficiency, but such effects were not prevented by giving glutathione, indicating that glutathione is not appreciably taken up by the cerebral cortex. Some of the oxygen used by mitochondria is known to be converted to hydrogen peroxide. We suggest that in glutathione deficiency, hydrogen peroxide accumulates and damages mitochondria. Glutathione, thus, has an essential function in mitochondria under normal physiological conditions. Observations on turnover and utilization of brain glutathione in newborn, preweaning, and adult rats show that (i) some glutathione turns over rapidly (t1/2, almost-equal-to 30 min in adults, almost-equal-to 8 min in newborns), (ii) several pools of glutathione probably exist, and (iii) brain utilizes plasma glutathione, probably by gamma-glutamyl transpeptidase-initiated pathways that account for some, but not all, of the turnover; thus, there is recovery or transport of cysteine moieties. These studies provide an animal model for the human diseases involving glutathione deficiency and are relevant to oxidative phenomena that occur in the newborn.