Phosphoramidon‐sensitive endothelin‐converting enzyme in vascular endothelial cells converts big endothelin‐1 and big endothelin‐3 to their mature form

FEBS Letters

Matsumura, Yasuo¹  Takaoka, Masanori¹  Kuninobu, Kazuko¹  Morimoto, Shiro¹  Tsukahara, Yaeko¹ 

[1] Department of Pharmacology, Osaka University of Pharmaceutical Sciences, 2-10-65 Kawai, Matsubara, Osaka 580, Japan

关键词: Endothelin-1;    Endothelin-3;    Big endothelin-1;    Big endothelin-3;    Metalloproteinase;    Phosphoramidon;   

DOI  :  10.1016/0014-5793(92)80870-M

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Incubation of big endothelin-3 (big ET-3_1–41) with the membrane fraction obtained from cultured endothelial cells (ECs) resulted in an increase in immunoreactive-ET (IR-ET). This increasing activity was markedly suppressed by phosphoramidon, which is known to inhibit the conversion of big ET-1_1–39 to ET-1_1–21. Reverse-phase HPLC of the incubation mixture of the membrane fraction with big ET-3 revealed one major IR-ET component corresponding to the elution position of synthetic ET-3_1–21. When the cultured ECs were incubated with big ET-3, a conversion to the mature ET-3, as well as an endogenous ET-1 generation, was observed. Both responses were markedly suppressed by phosphoramidon. By the gel filtration of 0.5% CHAPS-solubilized fraction of membrane pellets or ECs, the molecular mass of the proteinase which converts big ET-1 and big ET-3 to their mature form was estimated to be 300–350 kDa. Phosphoramidon almost completely abolished both converting activities of the proteinase. We conclude that the above type of phosphoramidon-sensitive metalloproteinase functions as an ET-converting enzyme to generate the mature form from big ET-1 and big ET-3 in ECs.

【 授权许可】

Unknown