Denault J B, Claing A, D'Orléans-Juste P, Sawamura T, Kido T, Masaki T, Leduc R
Department of Pharmacology, Medical School, Kyoto University, Japan.
FEBS Lett. 1995 Apr 10;362(3):276-80. doi: 10.1016/0014-5793(95)00249-9.
Endothelin-1 (ET-1) is the most potent vasoactive peptide known to date. The peptide is initially synthesized as an inactive precursor (proET-1) which undergoes proteolysis at specific pairs of basic amino acids to yield bigET-1. Production of ET-1 then proceeds by cleavage of bigET-1 by the endothelin converting enzyme (ECE). Here, we demonstrate that the in vitro cleavage of proET-1 by furin, a mammalian convertase involved in precursor processing, produced bigET-1. Upon further processing, bigET-1 was converted to biologically active ET-1. Furthermore, we demonstrate that the furin inhibitor, decanoyl-Arg-Val-Lys-Arg chloromethylketone, abolished production of ET-1 in endothelial cells.
内皮素-1（ET-1）是迄今为止已知的最有效的血管活性肽。该肽最初作为无活性前体（proET-1）合成，其在特定的碱性氨基酸对处进行蛋白水解以产生大内皮素-1（bigET-1）。然后通过内皮素转换酶（ECE）切割bigET-1来进行ET-1的产生。在此，我们证明，参与前体加工的哺乳动物转化酶弗林蛋白酶（furin）在体外切割proET-1可产生bigET-1。经过进一步加工，bigET-1被转化为具有生物活性的ET-1。此外，我们证明弗林蛋白酶抑制剂癸酰-精氨酸-缬氨酸-赖氨酸-精氨酸氯甲基酮可消除内皮细胞中ET-1的产生。
