Augmented death in immunostimulated astrocytes deprived of glucose: inhibition by an iron porphyrin FeTMPyP.
The present study shows that under glucose-deprived conditions immunostimulated astrocytes rapidly undergo death due to their increased susceptibility to endogenously produced peroxynitrite. Fe(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (FeTMPyP), but not the structurally related compounds ZnTMPyP and H(2)TMPyP, prevented the death in glucose-deprived immunostimulated astrocytes. Consistently, FeTMPyP, not ZnTMPyP and H(2)TMPyP, completely blocked the elevation of nitrotyrosine immunoreactivity (a marker of peroxynitrite) and the depolarization of the mitochondrial transmembrane potential in glucose-deprived immunostimulated astrocytes. The present data suggest that peroxynitrite may be associated with glial cell death during metabolic deterioration in the cerebral ischemic penumbra.
Choi
I Y
IY
Department of Chemistry and Division of Molecular Life Sciences, Seoul, South Korea.
Lee
S J
SJ
Nam
W
W
Park
J S
JS
Ko
K H
KH
Kim
H C
HC
Shin
C Y
CY
Chung
J H
JH
Noh
S K
SK
Choi
C R
CR
Shin
D H
DH
Kim
W K
WK
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D005290:Ferric Compounds / Q000494:pharmacology*; D005947:Glucose / Q000502:physiology*; D007371:Interferon-gamma / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D008981:Molsidomine / Q000031:analogs & derivatives / Q000494:pharmacology; D009566:Nitrates / Q000502:physiology; D011166:Porphyrins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D005290:Ferric Compounds; D008665:Metalloporphyrins; D009566:Nitrates; D011166:Porphyrins; C092399:meso-tetrakis(1-methyl-4-pyridiniumyl)porphyrin; C039642:peroxynitric acid; C002385:linsidomine; D007371:Interferon-gamma; D008981:Molsidomine; D005947:Glucose