TY - JOUR
T1 - (−)-Epigallocatechin-3-gallate inhibits human angiotensin-converting enzyme activity through an autoxidation-dependent mechanism
AU - Liu, Zhe
AU - Nakashima, Sayaka
AU - Nakamura, Toshiyuki
AU - Munemasa, Shintaro
AU - Murata, Yoshiyuki
AU - Nakamura, Yoshimasa
N1 - Publisher Copyright:
© 2017 Wiley Periodicals, Inc.
PY - 2017/9
Y1 - 2017/9
N2 - We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (−)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver–Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone.
AB - We investigated the molecular mechanisms involved in the angiotensin-converting enzyme (ACE) inhibition by (−)-epigallocatechin-3-gallate (EGCg), a major tea catechin. EGCg inhibited both the ACE activity in the lysate of human colorectal cancer cells and human recombinant ACE (rh-ACE) in a dose-dependent manner. Co-incubation with zinc sulfate showed no influence on the rh-ACE inhibition by EGCg, whereas it completely counteracted the inhibitory effect of ethylenediaminetetraacetic acid, a chelating-type ACE inhibitor. Although hydrogen peroxide was produced by the autoxidation of EGCg, hydrogen peroxide itself had little effect on the ACE activity. Conversely, the co-incubation of EGCg with borate or ascorbic acid significantly diminished the EGCg inhibition. A redox-cycling staining experiment revealed that rh-ACE was covalently modified by EGCg. A Lineweaver–Burk plot analysis indicated that EGCg inhibited the ACE activity in a non-competitive manner. These results suggested that EGCg might allosterically inhibit the ACE activity through oxidative conversion into an electrophilic quinone.
KW - (−)-epigallocatechin-3-gallate
KW - angiotensin-converting enzyme
KW - covalent modification
KW - non-competitive inhibition
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U2 - 10.1002/jbt.21932
DO - 10.1002/jbt.21932
M3 - Article
C2 - 28544013
AN - SCOPUS:85019629229
VL - 31
JO - Journal of Biochemical and Molecular Toxicology
JF - Journal of Biochemical and Molecular Toxicology
SN - 1095-6670
IS - 9
M1 - e21932
ER -