BNP molecular forms and processing by the cardiac serine protease corin.
BNP molecular forms and processing by the cardiac serine protease corin.
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DOI：
10.1016/b978-0-12-407680-8.00001-4
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发表时间：
2013
影响因子：
--
通讯作者：
Burnett JC Jr
中科院分区：
文献类型：
--
作者：
Ichiki T;Huntley BK;Burnett JC Jr
心脏激素B型利钠肽(BNP)是一种具有心脏肾脏保护作用的人体利钠肽，可作为心力衰竭(HF)的治疗和生物标志物。它的前激素proBNP1-108被前NPs转换酶Corin或Furin处理成无活性的NT-proBNP1-76和活性的BNP1-32。矛盾的是，循环中的NT-proBNP和BNP在心力衰竭时升高，导致使用BNP作为心力衰竭的敏感和预测标记物。这一悖论可以通过常规检测的“非特异性”性质和/或“活性BNP”的相对缺陷状态来解释，其特征是非活性ProBNP1-108的增加和活性BNP1-32的减少。因此，了解proBNP1-108加工的调节和转换酶Corin的作用对于理解HF的生理可能是重要的。Corin在心脏和肾脏中表达，可能在调节血压和心脏重塑方面发挥重要作用。Corin对proBNP1-108的加工可能受proBNP1-108的O-连接糖基化的控制。ProBNP1-108在HF中加工的潜在损害可能与转换酶Corin的失调有关，这可能为控制proBNP1-108在HF中的加工和激活提供了治疗机会。
The cardiac hormone, B-type natriuretic peptide (BNP), is one of human natriuretic peptides which possesses cardiorenal protective actions and is used as a therapeutic and a biomarker for heart failure (HF). Its prohormone, proBNP1-108, is processed by the proNPs convertases, corin or furin, to inactive NT-proBNP1-76 and active BNP1-32. Paradoxically, circulating NT-proBNP and BNP are elevated in HF leading to the use of BNP as a sensitive and predictive marker of HF. This paradox may be explained by the “non-specific” nature of conventional assays and/or a relative deficiency state of “active BNP” as characterized by an increase in inactive proBNP1-108 and a decrease in active BNP1-32. Therefore, understanding the regulation of proBNP1-108 processing and the role of the convertase corin may be important in understanding the physiology of HF. Corin is expressed in heart and kidney and may play an important role in regulating blood pressure and remodeling of the heart. The processing of proBNP1-108 by corin may be controlled by O-linked glycosylation of proBNP1-108. A potential impairment of proBNP1-108 processing in HF may be linked to dysregulation of the convertase corin, which may offer therapeutic opportunities to control proBNP1-108 processing and its activation in HF.