Murine glutathione S-transferase A1-1 in sickle transgenic mice.

Murine glutathione S-transferase A1-1 in sickle transgenic mice.
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镰状转基因小鼠中的鼠谷胱甘肽 S-转移酶 A1-1。

DOI:
10.1002/ajh.20941
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发表时间:
2007
影响因子:
12.8
通讯作者:
Nagel,RonaldL
Nagel,RonaldL
中科院分区:
医学1区
文献类型:
--
作者:
Ginzburg,YelenaZ;Andorfer,JohnH;Rybicki,AnneC;Fabry,MaryE;Nagel,RonaldL

文献摘要

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镰状细胞性贫血患者表现出轻度至中度的肾脏和肝脏损伤。谷胱甘肽S-转移酶A1 - 1在肾脏和肝脏损伤期间产生。我们假设镰状转基因小鼠的细胞损伤会导致血清和尿液中小鼠谷胱甘肽S-转移酶A1 - 1水平升高。通过ELISA测定了S+S-安的列斯、NY 1DD和对照小鼠血清和尿液中的鼠谷胱甘肽S-转移酶A1 - 1水平,结果显示,与对照小鼠相比,S+S-安的列斯小鼠血清中的鼠谷胱甘肽S-转移酶A1 - 1水平升高(P= 0.005),NY 1DD小鼠也是如此(P= 0.02,基线vs. 2天缺氧)。与对照组相比,S+S‐Antilles小鼠的血清肝酶(如天冬氨酸氨基转移酶和丙氨酸氨基转移酶)以及乳酸脱氢酶升高(分别为P= 0.000006、P = 0.0003和P = 0.029)。S+S‐Antilles小鼠以及缺氧应激下的NY 1DD小鼠的尿鼠谷胱甘肽S ‐转移酶A1‐1与对照组无显著差异。通过ELISA测定镰状转基因小鼠和对照小鼠尿液中的小鼠谷胱甘肽S-转移酶mu类,以确定近曲小管处肾小管损伤的位置;小鼠谷胱甘肽S-转移酶mu类低于检测限。这些结果表明,血清中鼠谷胱甘肽S-转移酶A1 - 1水平升高反映了肝损伤期间的释放,近端肾小管损伤不会导致明显的尿鼠谷胱甘肽S-转移酶A1 - 1。Am.血液学杂志82:911-915,2007.© 2007 Wiley利斯公司
Patients with sickle cell anemia exhibit mild to moderate renal and liver damage. GlutathioneS‐transferase A1‐1 is produced during kidney and liver damage. We hypothesized that cellular damage in sickle transgenic mice would lead to increased serum and urine murine glutathioneS‐transferase A1‐1 levels. Levels of murine glutathioneS‐transferase A1‐1 in the serum and urine of S+S‐Antilles, NY1DD, and control mice were measured by ELISA, which revealed that the serum of S+S‐Antilles mice, relative to controls, had elevated levels of murine glutathioneS‐transferase A1‐1 (P= 0.005) as did NY1DD mice (P= 0.02, baseline vs. 2‐day hypoxia). Serum liver enzymes, such as aspartate amino transferase and alanine amino transferase, as well as lactate dehydrogenase were increased in S+S‐Antilles mice relative to controls (P= 0.000006,P= 0.0003, andP= 0.029, respectively). Urine murine glutathioneS‐transferase A1‐1 of S+S‐Antilles mice, as well as NY1DD mice under hypoxic stress, was not significantly different from controls. Murine glutathioneS‐transferase class‐mu was measured by ELISA in the urine of sickle transgenic mice and control mice to define the location of tubular damage at the proximal convoluted tubule; murine GlutathioneS‐transferase class‐mu was below the limit of detection. These findings suggest that elevated levels of murine glutathioneS‐transferase A1‐1 in the serum reflect release during liver damage and that proximal tubular damage does not lead to appreciable urinary murine glutathioneS‐transferase A1‐1. Am. J. Hematol. 82:911–915, 2007. © 2007 Wiley‐Liss, Inc.