Glutamine protects intestinal epithelial cells: role of inducible HSP70.
Glutamine protects intestinal epithelial cells: role of inducible HSP70.
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DOI：
10.1152/ajpgi.1997.272.4.g879
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发表时间：
1997-04
期刊：
影响因子：
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通讯作者：
P. Wischmeyer;M. Musch;M. Madonna;R. Thisted;E. Chang
中科院分区：
文献类型：
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作者：
P. Wischmeyer;M. Musch;M. Madonna;R. Thisted;E. Chang
谷氨酰胺（Gln）保护肠道黏膜免受损伤，促进粘膜愈合。由于热休克蛋白（HSP）的诱导在应激条件下保护细胞，我们确定了Gln是否通过热休克蛋白诱导在肠上皮细胞系中对应激具有保护作用。向IEC-18细胞中添加Gln可诱导HSP70升高，mRNA也具有浓度依赖性。采用致死热（49℃）和氧化剂两种损伤方式，通过释放51Cr来测定细胞活力。gln处理的细胞对损伤的抵抗力明显增强。6-重氮-5-氧- l -去甲亮氨酸（DON）是Gln的一种非代谢类似物，可以诱导HSP70并保护细胞免受损伤，但效果低于Gln。这些发现表明，Gln对HSP70的诱导和细胞保护作用是通过代谢和非代谢机制介导的。为了确定HSP诱导是否对Gln和DON的作用至关重要，我们使用了阻断HSP诱导的槲皮素。槲皮素阻断了HSP70的诱导及Gln和DON的保护作用。我们认为Gln对肠上皮细胞的保护作用部分是通过HSP70诱导介导的。
Glutamine (Gln) protects gut mucosa against injury and promotes mucosal healing. Because the induction of heat shock proteins (HSP) protects cells under conditions of stress, we determined whether Gln conferred protection against stress in an intestinal epithelial cell line through HSP induction. Gln added to IEC-18 cells induces an increase in HSP70, a concentration-dependent effect also seen with mRNA. Two forms of injury, lethal heat (49 degrees C) and oxidant, were used, and viability was determined by 51Cr release. Gln-treated cells were significantly more resistant to injury. Treatment with 6-diazo-5-oxo-L-norleucine (DON), a nonmetabolizable analog of Gln, induced HSP70 and protected cells from injury, but less than Gln. These findings suggest that the effects of Gln on HSP70 induction and cellular protection are mediated by metabolic and nonmetabolic mechanisms. To determine whether HSP induction was central to the action of Gln and DON, quercetin, which blocks HSP induction, was used. Quercetin blocked HSP70 induction and the protective effect of Gln and DON. We conclude that the protective effects of Gln in intestinal epithelial cells are in part mediated by HSP70 induction.