Cain B M, Connolly K, Blum A C, Vishnuvardhan D, Marchand J E, Zhu X, Steiner D F, Beinfeld M C
Department of Pharmacology and Experimental Therapeutics, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
J Neurochem. 2004 Apr;89(2):307-13. doi: 10.1046/j.1471-4159.2003.02295.x.
Prohormone convertase (PC1) is found in endocrine cell lines that express cholecystokinin (CCK) mRNA and process pro CCK to biologically active products. Other studies have demonstrated that PC1 may be a one of the enzymes responsible for the endoproteolytic cleavages that occur in pro CCK during its biosynthesis and processing. Prohormone convertase 1 (PC1) has a distribution that is similar to cholecystokinin (CCK) in rat brain. A moderate to high percentage of CCK mRNA-positive neurons express PC1 mRNA. CCK levels were measured in PC1 knockout and control mice to assess the degree to which loss of PC1 changed CCK content. CCK levels were decreased 62% in hippocampus, 53% in amygdala and 57% in pons-medulla in PC1 knockout mice as compared to controls. These results are highly correlated with the colocalization of CCK and PC1. The majority of CCK mRNA-positive neurons in the pyramidal cell layer of the hippocampus express PC1 mRNA and greater than 50% of CCK mRNA-positive neurons in several nuclei of the amygdala also express PC1. These results demonstrate that PC1 is important for CCK processing. PC2 and PC5 are also widely colocalized with CCK. It may be that PC2, PC5 or another non-PC enzyme are able to substitute for PC1 and sustain production of some amidated CCK. Together these enzymes may represent a redundant system to insure the production of CCK.
激素原转化酶（PC1）存在于表达胆囊收缩素（CCK）mRNA并将前CCK加工成生物活性产物的内分泌细胞系中。其他研究表明，PC1可能是负责前CCK在其生物合成和加工过程中发生的内切蛋白水解切割的酶之一。激素原转化酶1（PC1）在大鼠脑中的分布与胆囊收缩素（CCK）相似。相当高比例的CCK mRNA阳性神经元表达PC1 mRNA。在PC1基因敲除小鼠和对照小鼠中测量CCK水平，以评估PC1缺失对CCK含量变化的影响程度。与对照组相比，PC1基因敲除小鼠海马中的CCK水平降低了62%，杏仁核中降低了53%，脑桥-延髓中降低了57%。这些结果与CCK和PC1的共定位高度相关。海马锥体细胞层中大多数CCK mRNA阳性神经元表达PC1 mRNA，杏仁核几个核中超过50%的CCK mRNA阳性神经元也表达PC1。这些结果表明，PC1对CCK的加工很重要。PC2和PC5也与CCK广泛共定位。可能是PC2、PC5或另一种非PC酶能够替代PC1并维持一些酰胺化CCK的产生。这些酶共同作用可能代表了一个冗余系统，以确保CCK的产生。
