Isoforms of alanine aminotransferases in human tissues and serum - Differential tissue expression using novel antibodies
Isoforms of alanine aminotransferases in human tissues and serum - Differential tissue expression using novel antibodies
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DOI：
10.1016/j.abb.2007.07.023
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发表时间：
2007-10-01
影响因子：
3.9
通讯作者：
Glinghammar, Bjoern
中科院分区：
文献类型：
--
作者：
Lindblom, Per;Rafter, Ingalill;Glinghammar, Bjoern
血清谷丙转氨酶（ALT）被用作肝毒性的临床指标。已经鉴定出两种形式的ALT， ALT1和ALT2，由不同的基因编码。不同的ALT蛋白在人体中的细胞和组织分布尚未确定，它们对血清的相对贡献也是未知的。在这里，我们描述了新型同工酶特异性ALT1和ALT2抗体的发展以及这些酶在人体细胞和器官中的表达。在正常人体组织中，ALT1在肝脏、骨骼肌和肾脏中高表达，在心肌中低表达，在胰腺中未检测到。在心脏和骨骼肌中检测到高的ALT2反应性，而在肝脏和肾脏中未发现ALT2表达。免疫组化结果显示，ALT1在肝细胞、肾小管上皮细胞和唾液腺上皮细胞中有较强的反应性，ALT2在肾上腺皮质、神经元细胞体、心肌细胞、骨骼肌纤维和内分泌胰腺中有表达。正常人血清中ALT抗体的免疫沉淀显示ALT1主要负责基础ALT活性。总之，这些结果指出了ALT1和ALT2在人体器官中的差异表达，并证实了对ALT测量可能产生的影响进行研究的必要性。(c) 2007爱思唯尔公司版权所有。
Serum alanine aminotransferase (ALT) is used as a clinical marker of hepatotoxicity. Two forms of ALT have been identified, ALT1 and ALT2, encoded by separate genes. The cellular and tissue distribution of the different ALT proteins has not been characterized in humans, and their relative contribution to serum is unknown. Here, we describe the development of novel isoenzyme specific ALT1 and ALT2 antibodies and the expression of the enzymes in human cells and organs. In normal human tissue, high expression of ALT1 was found in liver, skeletal muscle and kidney and low levels in heart muscle and not detectable in pancreas. High ALT2 reactivity was detected in heart and skeletal muscle, while no ALT2 expression was found in liver or kidney. Using immunohistochemistry, strong ALT1 reactivity was found in hepatocytes, renaltubular epithelial cells and in salivary gland epithelial cells, while ALT2 was expressed in adrenal gland cortex, neuronal cell bodies, cardiac myocytes, skeletal muscle fibers and endocrine pancreas. Inummoprecipitation using ALT antibodies on normal human serums showed ALT1 to be mainly responsible for basal ALT activity. Together, the results points to a differential expression of ALT1 and ALT2 in human organs and substantiate a need for investigations regarding the possible impacts on ALT measurements. (c) 2007 Elsevier Inc. All rights reserved.