title: Resveratrol reduces matrix metalloproteinase-2 activity induced by oxygen-glucose deprivation and reoxygenation in human cerebral microvascular endothelial cells.
abstract: The main pathophysiology in cerebral ischemia is the structural alteration in the neurovascular unit, coinciding with neurovascular matrix degradation. Among the human matrix metalloproteinases (MMPs), MMP-2 and -9, known as gelatinases, are the key enzymes for degrading type IV collagen, which is the major component of the basal membrane that surrounds the cerebral blood vessel. In the present study, we investigated the effects of resveratrol on cytotoxicity, reactive oxygen species (ROS), and gelatinases (MMP-2 and -9) in human cerebral microvascular endothelial cells exposed to 6 hours of oxygen-glucose deprivation and a subsequent 24 hours of reoxygenation with glucose (OGD/R), to mimic ischemia/reperfusion in vivo. Lactate dehydrogenase increased significantly, in comparison to that in the normoxia group. ROS was markedly increased in the OGD/R group, compared to normoxia. Correspondingly, ROS was significantly reduced with 50 μM of resveratrol. The proMMP-2 activity in the OGD/R group showed a statistically significant increase from the control cells. Resveratrol preconditioning decreased significantly the proMMP-2 in the cells exposed to OGD/R in comparison to that in the OGD/R group. Our results indicate that resveratrol regulates MMP-2 activity induced by OGD/R via its antioxidant effect, implying a possible mechanism related to the neuroprotective effect of resveratrol.
authors.affiliation: Dokuz Eylül University, Health Science Institute, Department of Molecular Medicine, Inciraltı, Izmir, Turkey. zahide.cavdar@deu.edu.tr
authors.forename: Zahide
authors.initials: Z
authors.lastname: Cavdar
authors.forename: Mehtap Y
authors.initials: MY
authors.lastname: Egrilmez
authors.forename: Zekiye S
authors.initials: ZS
authors.lastname: Altun
authors.forename: Nur
authors.initials: N
authors.lastname: Arslan
authors.forename: Nilgun
authors.initials: N
authors.lastname: Yener
authors.forename: Oya
authors.initials: O
authors.lastname: Sayin
authors.forename: Sermin
authors.initials: S
authors.lastname: Genc
authors.forename: Kursat
authors.initials: K
authors.lastname: Genc
authors.forename: Huray
authors.initials: H
authors.lastname: Islekel
authors.forename: Gulgun
authors.initials: G
authors.lastname: Oktay
authors.forename: Gul Guner
authors.initials: GG
authors.lastname: Akdogan
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001921:Brain / Q000098:blood supply*; D002545:Brain Ischemia; D002460:Cell Line; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology*; D004792:Enzyme Precursors / Q000378:metabolism; D018093:Gelatinases / Q000378:metabolism; D005947:Glucose / Q000008:administration & dosage*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects / Q000378:metabolism*; D008833:Microcirculation; D018696:Neuroprotective Agents / Q000494:pharmacology; D010100:Oxygen / Q000008:administration & dosage*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D000975:Antioxidants; D004792:Enzyme Precursors; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D007770:L-Lactate Dehydrogenase; D018093:Gelatinases; C069860:progelatinase; D020778:Matrix Metalloproteinase 2; D005947:Glucose; D000077185:Resveratrol; D010100:Oxygen