Epigallocatechin-3-gallate binding to MMP-2 inhibits gelatinolytic activity without influencing the attachment to extracellular matrix proteins but enhances MMP-2 binding to TIMP-2.
Although epigallocatechin-3-gallate (EGCg), a dominant component of green tea catechins, has been demonstrated to have anti-gelatinase properties, the molecular mechanisms by which EGCg blocks gelatinolytic activities remain unknown. We investigated whether EGCg may affect matrix metalloproteinase-2 (MMP-2) binding to native and denatured-type I collagen, and binding to the tissue inhibitor of metalloproteinase-2 (TIMP-2). Here, we report that EGCg forms a reversible complex with MMP-2, resulting in the inhibition of gelatinolytic activity of MMP-2. EGCg had no effect on the MMP-2 binding to immobilized native and denatured-type I collagen, but significantly enhanced pro- and activated MMP-2 binding to TIMP-2, as assessed by immunoprecipitation. These findings provide a new understanding of the molecular mechanisms underlying the inhibitory effect of EGCg on the gelatinolytic activity of MMP-2.
Cheng
Xian Wu
XW
Department of Geriatrics, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.
Kuzuya
Masafumi
M
Kanda
Shigeru
S
Maeda
Keiko
K
Sasaki
Takeshi
T
Wang
Qiu Lan
QL
Tamaya-Mori
Norika
N
Shibata
Tami
T
Iguchi
Akihisa
A
D002392:Catechin / Q000031:analogs & derivatives* / Q000737:chemistry*; D024042:Collagen Type I / Q000737:chemistry*; D004587:Electrophoresis, Agar Gel / Q000379:methods; D004789:Enzyme Activation; D016326:Extracellular Matrix Proteins / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D018093:Gelatinases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D006868:Hydrolysis; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry*; D011485:Protein Binding; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013379:Substrate Specificity; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000737:chemistry*
D024042:Collagen Type I; D016326:Extracellular Matrix Proteins; D019716:Tissue Inhibitor of Metalloproteinase-2; D002392:Catechin; D005780:Gelatin; C045651:epigallocatechin gallate; D018093:Gelatinases; D020778:Matrix Metalloproteinase 2