Regulatoin of Nectin-3 processing in the hippocampus mediared by MMP-9 under the chronic stress conditions

• Autorzy: Rejmak-Kozicka E. , Kalita K. , Kaczmarek L.
• Języki publikacji: EN

Abstrakty

EN

BACKGROUND AND AIMS: Nectin-3 is Ca2+-independent immunoglobulin (Ig)-like cell-cell adhesion molecule (CAMs) that is involved in the organization of various types of intercellular junctions, including interneuronal synapses. How cleavage of nectin-3 is regulated in neuronal cells is poorly understood. Emerging evidence suggest a role for CAMs and extracellular matrix remodeling in mechanisms that underlie the behavioral effects of stress. We tested the hypothesis that nectin-3 is involved in hippocampal region-specific effects induced by chronic stress. METHODS: Adult male Spraque-Dawley rats were restrained 6 h/ day for 21 days in wire mesh restrainers in their home cages. In the experiments that involved Western blot and gel zymography analyses, the rats were sacrificed by decapitation and CA1 or CA3 of the hippocampal formation were collected for synaptoneurosomes preparation. RESULTS: The results show an increase in the nectin-3 cleavage in synaptoneurosomal fraction obtained from the hippocampal CA1 field stimulated with glutamate in the group of rats subjected to chronic stress procedure as compared to the control group. Proteolytic cleavage of the nectin-3 results in the appearance of a 20 kDa nectin-3 derived fragment. The cleavage was inhibited by the MMP-9 inhibitor (inhibitor I). Moreover, we shown that the increased nectin-3 proteolysis under chronic stress conditions correlates with the elevated MMP-9 activity in the rat hippocampal CA1 fragment. In addition, taking into account the possibility of non-specific activity of the inhibitor we used we demonstrated experimentally its specific activity towards MMP-9. To test the connection between the nectin-3 shedding and activity of the MMP-9 in vitro experiments were performed on the hippocampal cultures. CONCLUSION: Obtained results clearly confirm that this protease causes fragmentation of the nectin-3. Furthermore, it was shown that this process depends on the activation of NMDA receptor and the presence of Ca2+/calmodulin.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2015
• Tom: 75
• Numer: Supl.
• Opis fizyczny: p.S42-S43

Twórcy

autor

Rejmak-Kozicka E.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kalita K.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Kaczmarek L.

• Laboratory of Neurobiology, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland