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 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 microM alpha-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-1beta. 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.
Vos
C M
CM
Department of Neurology, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Baltimore, Maryland 21287, USA.
Sjulson
L
L
Nath
A
A
McArthur
J C
JC
Pardo
C A
CA
Rothstein
J
J
Conant
K
K
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism / Q000633:toxicity*; D020783:Matrix Metalloproteinase 7 / Q000633:toxicity*; D020780:Matrix Metalloproteinase 9 / Q000633:toxicity*; D061965:Matrix Metalloproteinase Inhibitors; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000633:toxicity; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D007375:Interleukin-1; D061965:Matrix Metalloproteinase Inhibitors; D011994:Recombinant Proteins; D014810:Vitamin E; D007770:L-Lactate Dehydrogenase; D020783:Matrix Metalloproteinase 7; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1