학술논문

Structure-Dependent Inhibition of Gelatinases by Dietary Antioxidants in Rat Astrocytes and Sera of Multiple Sclerosis Patients
Document Type
Original Paper
Source
Neurochemical Research. March 2011 36(3):518-527
Subject
Matrix metalloproteinases
Polyphenols
Inflammation
Zymography
Astrocytes
Pathogenesis of multiple sclerosis
Language
English
ISSN
0364-3190
1573-6903
Abstract
We investigated whether polyphenols modulate the expression and activity of the enzymes gelatinases A (MMP-2) and B (MMP-9), involved in the pathogenesis of multiple sclerosis (MS). LPS-activated primary rat astrocytes were treated with the flavonoids quercetin (QRC) and cathechins [green tea extract (GTE)] and the non-flavonoids resveratrol (RSV) and tyrosol/hydroxytyrosol (Oliplus). As assessed by zymography and RT-PCR, RSV and Oliplus, but not QRC and GTE, dose-dependently inhibited the LPS-induced levels and mRNA expression of MMP-2 and MMP-9. By contrast, in cell-free systems direct inhibition of gelatinase activity in MS sera was determined by QRC and GTE, but not by RSV. Oliplus was only partially effective. Our results indicate that the flavonoids and non-flavonoids tested exert their inhibitory effect on MMPs, displaying different mechanisms of action, possibly related to their structure. Therefore, their combined use may represent a powerful tool for the down-regulation of MMPs in the course of MS.