Tissue Specificity of Human Angiotensin I-Converting Enzyme.
Tissue Specificity of Human Angiotensin I-Converting Enzyme.
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DOI：
10.1371/journal.pone.0143455
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Danilov SM
中科院分区：
文献类型：
--
作者：
Kryukova OV;Tikhomirova VE;Golukhova EZ;Evdokimov VV;Kalantarov GF;Trakht IN;Schwartz DE;Dull RO;Gusakov AV;Uporov IV;Kost OA;Danilov SM
血管紧张素转换酶(ACE)是一种表达于内皮细胞和上皮细胞表面的1型膜糖蛋白，它代谢多种多肽，在血压调节、血管重塑以及生殖功能中起关键作用。血管紧张素转换酶在生物体液中也以可溶形式存在，其中精液中的血管紧张素转换酶含量最高--是血液中的50倍以上。我们使用一组抗人ACE 17个表位的单抗对肺和精液ACE进行了构象指纹分析，并确定了潜在的ACE结合伙伴对mAbs与这两种不同ACE结合的影响。ACEs胰酶消化质谱仪证实，肺脏和精液中的单抗与ACEs结合的模式明显不同，这反映了这些ACEs局部构象的差异，这可能是由于ACEs胰酶消化质谱学证实，肺内皮细胞和附睾腺/前列腺(精液ACE的来源)上皮细胞的ACE糖基化模式不同。精液和肺ACE局部构象的显著差异，以及ACE结合伙伴对与这些ACE结合的单抗的影响，表明ACE功能和附睾腺上皮细胞和肺毛细血管内皮细胞对ACE功能和脱落的调节不同。血管紧张素转换酶局部构象的差异可能是产生区分组织特异性ACE的单抗的基础。
Angiotensin-converting enzyme (ACE), which metabolizes many peptides and plays a key role in blood pressure regulation and vascular remodeling, as well as in reproductive functions, is expressed as a type-1 membrane glycoprotein on the surface of endothelial and epithelial cells. ACE also presents as a soluble form in biological fluids, among which seminal fluid being the richest in ACE content - 50-fold more than that in blood. We performed conformational fingerprinting of lung and seminal fluid ACEs using a set of monoclonal antibodies (mAbs) to 17 epitopes of human ACE and determined the effects of potential ACE-binding partners on mAbs binding to these two different ACEs. Patterns of mAbs binding to ACEs from lung and from seminal fluid dramatically differed, which reflects difference in the local conformations of these ACEs, likely due to different patterns of ACE glycosylation in the lung endothelial cells and epithelial cells of epididymis/prostate (source of seminal fluid ACE), confirmed by mass-spectrometry of ACEs tryptic digests. Dramatic differences in the local conformations of seminal fluid and lung ACEs, as well as the effects of ACE-binding partners on mAbs binding to these ACEs, suggest different regulation of ACE functions and shedding from epithelial cells in epididymis and prostate and endothelial cells of lung capillaries. The differences in local conformation of ACE could be the base for the generation of mAbs distingushing tissue-specific ACEs.