Troglitazone inhibits glutamine metabolism in rat mesangial cells.
Troglitazone inhibits glutamine metabolism in rat mesangial cells.
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Troglitazone 抑制大鼠系膜细胞中的谷氨酰胺代谢。
DOI：
10.1152/ajpendo.2002.282.1.e231
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Welbourne,Tomas
中科院分区：
文献类型：
--
作者：
Routh,Robert;McCarthy,Kevin;Welbourne,Tomas
Troglitazone 是一种过氧化物酶体增殖物激活受体-γ 激动剂，已被证明可以在 2 型糖尿病实验模型中阻止系膜扩张，并直接作用于大鼠系膜细胞。由于谷氨酰胺是细胞生物合成过程的前体，我们询问曲格列酮在这些条件下是否会抑制系膜细胞谷氨酰胺代谢。将汇合的单层大鼠系膜细胞在曲格列酮或媒介物 (DMSO) 存在下在 RPMI 培养基中孵育。曲格列酮对谷氨酰胺的利用和丙氨酸的形成产生剂量依赖性的减少，与单层胶原蛋白-糖胺聚糖含量的减少有关。尽管谷氨酰胺的吸收减少，但铵的形成并未减少，这与通过脱氨途径的谷氨酸通量增加一致。丙氨酸氨基转移酶的可测定活性下降了 63%，而可测定的谷氨酸脱氢酶保持不变。在对照单层细胞中，释放的铵+丙氨酸+谷氨酸氮的总和占谷氨酰胺氮吸收的<75%。在曲格列酮处理的单层细胞中，所有吸收的谷氨酰胺氮都可以被解释为释放到培养基中的铵态氮。这些结果与曲格列酮减少谷氨酰胺代谢，特别是大鼠系膜细胞中与胶原糖胺聚糖含量减少相关的转氨途径一致。
Troglitazone is a peroxisome proliferator-activated receptor-γ agonist that has been shown to halt mesangium expansion in experimental models of type 2 diabetes mellitus and to act directly on rat mesangial cells. Because glutamine serves as the precursor for cellular biosynthetic processes, we asked whether troglitazone would inhibit mesangial cell glutamine metabolism under these conditions. Confluent monolayers of rat mesangial cells were incubated in RPMI medium in the presence of troglitazone or vehicle (DMSO). Troglitazone effected a dose-dependent reduction in glutamine utilization and in alanine formation, associated with a decrease in monolayer collagen-glycosaminoglycan content. Despite the reduced glutamine uptake, ammonium formation did not decrease, consistent with increased glutamate flux through the deamination pathway. Assayable activity of the alanine aminotransferase decreased by 63%, whereas assayable glutamate dehydrogenase remained unchanged. In control monolayers, the sum of ammonium plus alanine plus glutamate nitrogen released accounted for <75% of the glutamine nitrogen uptake. In troglitazone-treated monolayers, all of the glutamine nitrogen taken up could be accounted for as ammonium nitrogen released into the medium. These results are consonant with troglitazone reducing glutamine metabolism and specifically the transamination pathway in rat mesangial cells associated with a reduction in collagen-glycosaminoglycan content.