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Intracellular pH-dependent peroxynitrite-evoked synergistic death of glucose-deprived astrocytes

Title
Intracellular pH-dependent peroxynitrite-evoked synergistic death of glucose-deprived astrocytes
Authors
Ju C.Oh Y.J.Han B.H.Kim H.-S.Kim H.-C.Kim W.-K.
Ewha Authors
김원기김희선
SCOPUS Author ID
김희선scopus
Issue Date
2004
Journal Title
Free Radical Biology and Medicine
ISSN
0891-5849JCR Link
Citation
vol. 37, no. 8, pp. 1160 - 1169
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
Previously, we reported that glucose-deprived astrocytes were highly vulnerable to peroxynitrite (ONOO -). Here we demonstrate that the increased vulnerability caused by glucose deprivation and ONOO - depends on intracellular pH. The ONOO - releasing reagent 3-morpholinosydnonimine (SIN-1) markedly induced the release of lactate dehydrogenase (LDH, the marker of cytotoxicity) in glucose-deprived astrocytes. Morphological studies and caspase activity assay showed that astrocytes treated together with glucose deprivation and ONOO - died mostly in a necrotic mode. Alkalinization of pH from 7.4 to 7.8 increased LDH release, whereas acidification from pH 7.4 to 7.0 decreased it. However, intracellular pH (pH i), not extracellular pH (pH e), appeared to play a critical role in the synergistic death. Thus, without a change in pH e (7.4) cytosolic acidification by a weak acid salt, sodium acetate, and a Na +/H + antiporter inhibitor, amiloride, reduced LDH release. In contrast, a weak base, NH 4Cl, and a Na +/H + antiporter stimulator, monensin, increased pH i and greatly enhanced LDH release. The augmented death was found to be due, in part, to the preceding decrease in the level of reduced glutathione, the ONOO - scavenger, and collapse of the mitochondrial transmembrane potential at alkaline pH. © 2004 Elsevier Inc. All rights reserved.
DOI
10.1016/j.freeradbiomed.2004.07.011
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자연과학대학 > 화학·나노과학전공 > Journal papers
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