GLUTATHIONE IS REQUIRED FOR INTESTINAL FUNCTION
GLUTATHIONE IS REQUIRED FOR INTESTINAL FUNCTION
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DOI：
10.1073/pnas.87.5.1715
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发表时间：
1990-03-01
影响因子：
11.1
通讯作者：
MEISTER, A
中科院分区：
文献类型：
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作者：
MARTENSSON, J;JAIN, A;MEISTER, A
谷氨酰胺（GSH）缺乏症在小鼠中通过给予丁硫酰亚胺磺酰亚胺导致空肠和结肠上皮细胞的严重变性。这可以通过给予GSH单酯（口服或i.p.）以及给予GSH（口服，但不是腹腔注射）。腹膜内给药导致高血浆GSH水平，但不会明显增加肠粘膜或胰腺中的GSH水平。这些和以前对透镜、肺、淋巴细胞、肝、心脏和骨骼肌的研究表明，即使有，也很少有完整的GSH从血浆转运到这些组织。细胞可以通过涉及其裂解、产物摄取和细胞内GSH合成的途径来利用细胞外GSH。胃肠道的上皮细胞可以使用该途径，并且还可以通过可能涉及二肽或GSH转运的机制摄取内腔GSH（其部分来自胆汁）。提示胆汁GSH具有保护肠粘膜的功能。GSH的施用可以保护胃肠道上皮，并且还可以用作胃肠道和其他组织中细胞内GSH合成的半胱氨酸部分的良好来源。GSH递送剂如GSH酯的施用在增加GSH的细胞和线粒体水平方面比GSH的施用更有效。
Glutathione (GSH) deficiency produced in mice by giving buthionine sulfoximine leads to severe degeneration of the epithelial cells of the jejunum and colon. This is prevented by giving GSH monoester (orally or i.p.) and also by giving GSH (orally, but not i.p.). The i.p. administration leads to high plasma levels of GSH but does not appreciably increase GSH levels in intestinal mucosa or pancreas. These and previous studies on lens, lungs, lymphocytes, liver, heart, and skeletal muscle indicate that there is very little, if any, transport of intact GSH from plasma to these tissues. Cells can use extracellular GSH by a pathway involving its cleavage, uptake of products and intracellular GSH synthesis. Epithelial cells of the gastrointestinal tract may use this pathway and can also take up lumenal GSH (which arises partly from the bile) by a mechanism(s) that may involve transport of dipeptides or of GSH. It is suggested that biliary GSH normally functions in the protection of intestinal mucosa. Administration of GSH may be protective of the gastrointestinal epithelium and may also serve as a good source of cysteine moieties for intracellular GSH synthesis in the gastrointestinal tract and in other tissues. Administration of GSH delivery agents such as GSH esters is more effective than administration of GSH in increasing cellular and mitochondrial levels of GSH.