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氨暴露对胶质瘤细胞的影响:通过扩散加权和高分辨率核磁共振波谱研究细胞体积和有机渗透溶质的变化。

Effects of ammonia exposition on glioma cells: changes in cell volume and organic osmolytes studied by diffusion-weighted and high-resolution NMR spectroscopy.

作者信息

Zwingmann C, Flögel U, Pfeuffer J, Leibfritz D

机构信息

Department of Chemistry, University of Bremen, Germany.

出版信息

Dev Neurosci. 2000 Sep-Dec;22(5-6):463-71. doi: 10.1159/000017476.

DOI:10.1159/000017476
PMID:11111163
Abstract

NH(4)Cl (10 mM) caused a sustained increase in the cell volume in immobilized, perfused F98 glioma cells to approx. 125% of control after 3 h, as measured by diffusion-weighted (1)H NMR spectroscopy. Concomitantly, the glutamine (Gln) concentration increased by 130%, accompanied by a marked decrease in cytosolic osmolytes, i.e. myo-inositol and taurine, determined from (1)H NMR spectra of PCA extracts. Inhibition of Gln synthetase partially prevented the increase in water content. While losses of organic osmolytes are also observed under hypotonic conditions, the rapid cell swelling is followed by the regulatory cell volume decrease (RVD), and is accompanied by decreased cytosolic Gln. We suggest that the rise in intracellular osmolarity, which is attributed to NH(4)Cl metabolism to Gln, but also to alanine (Ala), is not compensated by the release of other osmolytes, and causes cell swelling without RVD.

摘要

通过扩散加权氢核磁共振波谱法测定,10 mM的氯化铵(NH₄Cl)使固定灌注的F98胶质瘤细胞的细胞体积在3小时后持续增加至对照的约125%。与此同时,谷氨酰胺(Gln)浓度增加了130%,同时从PCA提取物的氢核磁共振波谱确定,胞质渗透溶质即肌醇和牛磺酸显著减少。谷氨酰胺合成酶的抑制部分阻止了水分含量的增加。虽然在低渗条件下也观察到有机渗透溶质的损失,但快速的细胞肿胀之后是调节性细胞体积减小(RVD),并伴有胞质Gln减少。我们认为,细胞内渗透压的升高归因于NH₄Cl代谢为Gln,但也归因于丙氨酸(Ala),未通过其他渗透溶质的释放得到补偿,从而导致细胞肿胀而无RVD。

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