DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues
DPP8 and DPP9 expression in cynomolgus monkey and Sprague Dawley rat tissues
复制标题
DOI：
10.1016/j.regpep.2013.07.003
复制
发表时间：
2013-09-10
影响因子：
--
通讯作者：
Moyer, Carolyn F.
中科院分区：
文献类型：
--
作者：
Harstad, Eric. B.;Rosenblum, Jonathan S.;Moyer, Carolyn F.
二肽基肽酶（DPPs）是一种蛋白水解酶，通过降解信号肽来调节许多生理系统。DPP 8和DPP 9在序列、细胞定位和表达水平上与DPP 4不同，因此意味着不同的功能。然而，DPP 8和DPP 9的表达需要进一步描述。我们使用三种独立的方法在mRNA、蛋白质和功能水平上评估了DPP 4、DPP 8和DPP 9的表达，以更好地了解每种酶的局部生理贡献。选择Sprague道利大鼠和食蟹猴进行DPP 4、DPP 8和DPP 9表达谱分析，以代表药物临床前安全性评价常用的动物种属。除了新获得的抗体用于免疫组织化学定位外，还应用了一种新的DPP蛋白酶活性的Xcad测定法。这种组合的方法可以促进蛋白酶表达的功能评价，这对于理解生理相关性是重要的。几乎没有观察到种间差异。组织mRNA和蛋白质水平通常与功能性DPP 4和DPP 8/9酶活性相关。所有三种蛋白质都见于上皮细胞、淋巴样细胞和一些内皮细胞和血管平滑肌细胞。组合的DPP 8/DPP 9酶活性在整个组织中以比非肾DPP 4低约10倍的水平均匀地在细胞内。在大鼠和猴的大多数非肾脏组织中检测到每种DPP的一致水平。DPP 4是普遍存在的，主要在上皮细胞和内皮细胞的细胞膜上检测到，并且在肾脏中最大。这些表达模式表明，DPP 8和DPP 9在组织中的作用可能相似，并且它们的作用可能与DPP 4部分重叠。(C)2013爱思唯尔有限公司版权所有。
Dipeptidyl peptidases (DPPs) are proteolytic enzymes that regulate many physiological systems by degrading signaling peptides. DPP8 and DPP9 are distinct from DPP4 in sequence, cellular localization and expression levels, thus implying distinct functions. However, DPP8 and DPP9 expression needs further delineation. We evaluated DPP4, DPP8 and DPP9 expression using three independent methods at the mRNA, protein, and functional levels to better understand the local physiological contribution of each enzyme. Sprague Dawley rats and cynomolgus monkeys were selected for DPP4, DPP8 and DPP9 expression profiling to represent animal species commonly utilized for drug preclinical safety evaluation. A novel Xhibit assay of DPP protease activity was applied in addition to newly available antibodies for immunohistochemical localization. This combined approach can facilitate a functional evaluation of protease expression, which is important for understanding physiological relevance. Few inter-species differences were observed. Tissue mRNA and protein levels generally correlated to functional DPP4 and DPP8/9 enzymatic activity. All three proteins were seen in epithelial cells, lymphoid cells and some endothelial and vascular smooth muscle cells. Combined DPP8/DPP9 enzymatic activity was uniformly intracellular across tissues at approximately 10-fold lower levels than non-renal DPP4. Consistent levels of each DPP were detected among most non-renal tissues in rats and monkeys. DPP4 was ubiquitous, principally detected on cell membranes of epithelial and endothelial cells and was greatest in the kidney. The expression patterns suggest that DPP8 and DPP9 may act similarly across tissues, and that their actions might in part overlap with DPP4. (C) 2013 Elsevier B.V. All rights reserved.