Cytotoxicity by matrix metalloprotease-1 in organotypic spinal cord and dissociated neuronal cultures

Extracellular matrix (ECM) proteins, including collagens and laminins, are critical to the structure of the neuronal synapse and may also be involved in cell survival. In the present study, we therefore examined the possibili ty that select ECM degrading proteins might be toxic to organotypic spinal cord and dissociated neuronal cultures. Of those proteins tested, including MMP-1, -7, and -9, we observed that MMP-1 was toxic to spinal cord culture s as determined by release of lactic acid dehydrogenase as web as uptake of propidium iodide. Pretreatment of cell cultures with 50 mu M alpha-tocophe rol partially reversed these effects. We also observed that MMP-1 was toxic to human neurons grown in dissociated cultures and that increased amounts of MMP-1 were released by astrocytes following their stimulation with IL-1 beta. These results suggest that further studies may be warranted to determ ine whether MMP-1 contributes to neurodegenerative conditions in which acti vated astrocytes may play a role. (C) 2000 Academic Press.