Cytotoxicity by Matrix Metalloprotease-1 in Organotypic Spinal Cord and Dissociated Neuronal Cultures

• Published in: Experimental neurology Vol. 163; no. 2; pp. 324 - 330
• Main Authors: Vos, Catharina M.P., Sjulson, Lucas, Nath, Avindra, McArthur, Justin C., Pardo, Carlos A., Rothstein, Jeffrey, Conant, Katherine
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01-06-2000; Elsevier
• Subjects: Animals; Animals, Newborn; Astrocytes - drug effects; Astrocytes - metabolism; Biological and medical sciences; Cells, Cultured; Humans; Interleukin-1 - pharmacology; L-Lactate Dehydrogenase - metabolism; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 1 - toxicity; Matrix Metalloproteinase 7 - toxicity; Matrix Metalloproteinase 9 - toxicity; Matrix Metalloproteinase Inhibitors; Medical sciences; Nervous system involvement in other diseases. Miscellaneous; Neurology; Neurons - drug effects; Neurons - metabolism; Rats; Recombinant Proteins - toxicity; Spinal Cord - drug effects; Spinal Cord - metabolism; Vitamin E - pharmacology; Cell culture; Spinal cord; Rat; Enzyme; Rodentia; Central nervous system; Organotypic culture; Metalloendopeptidases; Cytotoxicity; Peptidases; Vertebrata; Mammalia; Neuron; Animal; Hydrolases; Extracellular matrix; Matrilysin
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2000.7388

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 possibility 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 cultures as determined by release of lactic acid dehydrogenase as well as uptake of propidium iodide. Pretreatment of cell cultures with 50 μM α-tocopherol 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-1β. These results suggest that further studies may be warranted to determine whether MMP-1 contributes to neurodegenerative conditions in which activated astrocytes may play a role.