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The effects of curcumin, mangiferin, resveratrol and other natural plant products on aminopeptidase B activity.

Abstract：

:Aminopeptidase B (Ap-B) is a Zn2+-aminopeptidase of the M1 family which is implicated, in conjunction with the nardilysin endoprotease, in the generation of miniglucagon, a peptide involved in the maintenance of glucose homeostasis. Other in vivo physiological roles have been established for this vertebrate enzyme, such as the processing of Arg-extended forms of human insulin and cholecystokinin 9 and the degradation of viral epitopes in the cytoplasm. Among M1 family members, Ap-B is phylogenetically close to leukotriene A4 hydrolase (LTA4H), a bi-functional aminopeptidase also able to transform LTA4 in LTB4 (a lipid mediator of inflammation). As the activities of LTA4H are reported to be inhibited by resveratrol, a polyphenolic molecule from red wine, the effect of this molecule was investigated on the Ap-B activity. Several other active phenolic compounds produced in plants were also tested. Among them, curcumin and mangiferin are the most effective inhibitors. Dixon analysis indicates that curcumin is a non-competitive inhibitor with a Ki value of 46 μmol.L-1. Dixon and Lineweaver-Burk representations with mangiferin show a mixed non-competitive inhibition with Ki' and Ki values of 194 μmol.L-1 and 105 μmol.L-1, respectively. At 200 μmol.L-1, no significant effect was observed with caffeic, chlorogenic, ferulic, salicylic and sinapic acids as well as with resveratrol. Analyses on the 3D-structure of LTA4H with resveratrol (pdb: 3FTS) and the Ap-B 3D-model allow hypothesis to explain theses results.

journal_name

Biochem Biophys Res Commun

journal_title

Biochemical and biophysical research communications

authors

Cadel S,Darmon C,Désert A,Mahbouli M,Piesse C,Ghélis T,Lafont R,Foulon T

doi

10.1016/j.bbrc.2019.02.143

subject

Has Abstract

pub_date

2019-05-14 00:00:00

pages

832-837

issue

4

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(19)30356-0

journal_volume

512

pub_type

杂志文章

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