Augmented death in immunostimulated astrocytes deprived of glucose: inhibition by an iron porphyrin FeTMPyP

The present study shows that under glucose-deprived conditions immunostimul ated astrocytes rapidly undergo death due to their increased susceptibility to endogenously produced peroxynitrite. Fe(III)tetrakis(N-methyl-4'-pyridy l)porphyrin (FeTMPyP), but not the structurally related compounds ZnTMPyP a nd H2TMPyP, prevented the death in glucose-deprived immunostimulated astroc ytes. Consistently, FeTMPyP, not ZnTMPyP and H2TMPyP, completely blocked th e elevation of nitrotyrosine immunoreactivity (a marker of peroxynitrite) a nd the depolarization of the mitochondrial transmembrane potential in gluco se-deprived immunostimulated astrocytes. The present data suggest that pero xynitrite may be associated with glial cell death during metabolic deterior ation in the cerebral ischemic penumbra. (C) 2001 Published by Elsevier Sci ence B.V. All rights reserved.