Corin Is Present in the Normal Human Heart, Kidney, and Blood, with Pro-B-Type Natriuretic Peptide Processing in the Circulation
Corin Is Present in the Normal Human Heart, Kidney, and Blood, with Pro-B-Type Natriuretic Peptide Processing in the Circulation
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DOI：
10.1373/clinchem.2010.153908
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发表时间：
2011-01-01
影响因子：
9.3
通讯作者：
Burnett, John C., Jr.
中科院分区：
文献类型：
--
作者：
Ichiki, Tomoko;Huntley, Brenda K.;Burnett, John C., Jr.
背景：B型利钠肽（BNP）在心力衰竭（HF）时被激活，由corin加工成活性形式。corin基因在人类心脏和肾脏中表达，但corin蛋白在心脏、肾脏和循环中的表达，沿着proBNP是否被循环corin.METHODS加工，仍然未知：我们通过免疫染色和Western印迹检测了corin蛋白在人类心脏和肾脏中的表达，并通过ELISA评估了循环corin浓度。我们通过免疫沉淀和Western blot检测了血清和血浆中组氨酸标记的（Histag）proBNP（1-108）的加工过程，并对加工形式进行了测序。结果：正常人心脏和肾脏显示corin的存在，尤其是在血管周围的细胞中。corin和proBNP（1-108）均存在于健康人血浆中，男性循环corin显著高于女性（P < 0.0001），corin与年龄呈正相关（P = 0.0497，r = 0.27）。在新鲜的正常血浆和血清中，His-标签proBNP（1-108）被加工成较低分子量形式，证实为BNP。男性的脑钠肽加工水平高于女性（P = 0.041），与血浆corin浓度呈正相关（P = 0.041，r = 0.65）。结论：我们的结果支持脑钠肽原（1-108）可能在心脏外的前蛋白转化酶存在的循环中被加工的观点。此外，性别可能会影响这一过程，因为corin浓度在男性中更高。这些发现可能对人类proBNP/corin系统具有重要的生理和病理生理意义。(C)2010年美国临床化学协会
BACKGROUND: B-type natriuretic peptide (BNP), which is activated in heart failure (HF), is processed to an active form by corin. The corin gene is expressed in the human heart and kidney, but corin protein expression in the heart, kidney, and circulation, along with whether proBNP is processed by circulating corin, remains unknown.METHODS: We examined corin protein expression by immunostaining and Western blot in human heart and kidney, and we assessed the circulating corin concentration by ELISA. We examined histidine-tagged (Histag) proBNP(1-108) processing in serum and plasma by immunoprecipitation and Western blot and sequenced the processed form.RESULTS: Normal human heart and kidney displayed the presence of corin, especially in cells around the vasculature. Both corin and proBNP(1-108) were present in the plasma of healthy human subjects, with circulating corin significantly higher in men than women (P < 0.0001) and a positive correlation of corin to age (P = 0.0497, r = 0.27). In fresh normal plasma and serum, His-tag proBNP(1-108) was processed to a lower molecular weight form confirmed to be BNP. Processed BNP was higher in men than women (P = 0.041) and was positively correlated to plasma corin concentrations (P = 0.041, r = 0.65).CONCLUSIONS: Our results support the concept that proBNP(1-108) may be processed outside of the heart in the circulation where the proprotein convertase is present. Moreover, sex may impact this process, since corin concentrations are higher in men. These findings may have important physiologic and pathophysiologic implications for the proBNP/corin system in the human. (C) 2010 American Association for Clinical Chemistry