Molecular Mechanisms of MMP9 Expression in Astrocytes Induced by Heme and Iron

FieldValue
dc.contributor.authorHasim, Mohamed Shaad
dc.date.accessioned2012-12-07T19:09:25Z
dc.date.available2012-12-07T19:09:25Z
dc.date.created2012
dc.date.issued2012
dc.identifier.urihttp://hdl.handle.net/10393/23575
dc.identifier.urihttp://dx.doi.org/10.20381/ruor-6252
dc.description.abstractThe disruption of the blood-brain barrier (BBB) occurs after ischemic and hemorrhagic stroke and contributes to secondary brain damage. Matrix metalloproteinase-9 (MMP9) has been identified to be the main mediator of post-stroke BBB disruption. It is unknown whether deposition of heme/iron in the brain following stroke would affect MMP9 expression. In this study, I have demonstrated that heme/iron up-regulated MMP9 expression in rat astrocytes and that this upregulation was most likely due to reactive oxygen species (ROS) generated by heme/iron deposition on cells. ROS can activate AP-1 and NFκB signaling pathways which were responsible for increased MMP9 expression. Inhibiting AP-1 and NFκB decreased MMP9 expression. Heme/iron deposition also activated Nrf-2 and increased the expression of neuroprotective heme oxygenase-1. My study suggests that heme and iron deposition generates ROS and increases MMP9 expression through AP-1 and NFκB signaling pathways and that targeting these pathways or clearance of heme and iron may modulate MMP9 expression for reduced damage.
dc.language.isoen
dc.publisherUniversité d'Ottawa / University of Ottawa
dc.subjectMatrix Metalloproteinase 9
dc.subjectMMP9
dc.subjectBlood Brain Barrier
dc.subjectHeme
dc.subjectIschemic Stroke
dc.titleMolecular Mechanisms of MMP9 Expression in Astrocytes Induced by Heme and Iron
dc.typeThesis
dc.faculty.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
dc.contributor.supervisorZhang, Wandong
dc.embargo.termsimmediate
dc.degree.nameMSc
dc.degree.levelmasters
dc.degree.disciplineMédecine / Medicine
thesis.degree.nameMSc
thesis.degree.levelMasters
thesis.degree.disciplineMédecine / Medicine
uottawa.departmentMédecine cellulaire et moléculaire / Cellular and Molecular Medicine
CollectionThèses, 2011 - // Theses, 2011 -

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