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Involvement of MMPs in delayed neuronal death after global ischemia
Teresa Zalewska1, Małgorzata Ziemka-Nałecz, Anna Sarnowska
1Laboratory of Molecular Neuropathology, Department of Neurochemistry, Medical Research Centre, Polish Academy of Sciences, 5 Pawiński St., 02-106 Warsaw, Poland. terezal@cmdik.pan.pl.
Abstract:
Spatial and temporal relations between metalloproteinase (MMP-2 and MMP-9) activation and laminin degradation in gerbil hippocampus after transient cerebral ischemia has been studied. Activity of MMPs was determined by gelatin zymography in homogenates from dorsal (DP, an equivalent of CA1 sector) and abdominal (AbP, containing CA2-4 and gyrus dentatus) parts of hippocampus. A significant activation of both investigated metalloproteinases was found at 72 h of recovery. Whereas MMP-2 up-regulation did not show any spatial preferences, the increase of MMP-9 activity was observed exclusively in DP. Activation of MMP-9 at this time point correlated spatially with degradation of laminin-protein of extracellular matrix. These results show that MMP pathway may function as a component of delayed neuronal death cascade in the apoptogenic CA1 sector after transient global ischemia.
Insights
Metalloproteinase (MMP-2 and MMP-9) activation and laminin degradation were studied in gerbil hippocampus after ischemia. MMP-9 activation correlated with laminin degradation in the CA1 sector, suggesting a role in delayed neuronal death.
Area of Science:
- Neuroscience
- Biochemistry
Background:
- Transient cerebral ischemia can lead to delayed neuronal death.
- Matrix metalloproteinases (MMPs) are implicated in tissue remodeling and degradation.
Purpose of the Study:
- To investigate the spatial and temporal relationship between matrix metalloproteinase (MMP-2 and MMP-9) activation and laminin degradation in the gerbil hippocampus following transient cerebral ischemia.
- To determine the role of MMPs in the delayed neuronal death cascade in the CA1 sector.
Main Methods:
- Gelatin zymography was used to assess the activity of MMP-2 and MMP-9 in homogenates from dorsal (DP) and abdominal (AbP) parts of the gerbil hippocampus.
- Laminin degradation was assessed in correlation with MMP activity.
Main Results:
- Both MMP-2 and MMP-9 showed significant activation 72 hours after recovery from ischemia.
- MMP-9 activation was specifically observed in the dorsal hippocampus (DP), corresponding to the CA1 sector.
- Increased MMP-9 activity correlated spatially with laminin degradation in the extracellular matrix.
Conclusions:
- The MMP pathway, particularly MMP-9, plays a role in laminin degradation in the CA1 sector after transient global ischemia.
- MMP activation is a component of the delayed neuronal death cascade in the vulnerable CA1 hippocampal sector.