Protection by a manganese porphyrin of endogenous peroxynitrite-induced death of glial cells via inhibition of mitochondrial transmembrane potential decrease

In Young Choi, Sun Jung Lee, Chung Ju, Wonwoo Nam, Hyoung Chun Kim, Kwang Ho Ko, Won Ki Kim

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

In the cerebral ischemic penumbra, progressive metabolic deterioration eventually leads to death of glial cells. The exact mechanism for the death of glial cells is unclear. Here we report that under glucose-deprived conditions immunostimulated glial cells rapidly underwent death via production of large amounts of peroxynitrite. The cell-permeable Mn(III)tetrakis(N-methyl-4'-pyridyl)porphyrin (MnTMPyP) caused a concentration-dependent attenuation of the increased death in glucose-deprived immunostimulated glial cells. The structurally related compound H2TMPyP, which lacks metals, did not attenuate this augmented cell death. MnTMPyP prevented the elevation in nitrotyrosine immunoreactivity (a marker of ONOO-) in glucose-deprived immunostimulated glial cells. In glucose-deprived glial cells, MnTMPyP also completely blocked the augmented death and nitrotyrosine immunoreactivity induced by the ONOO-producing reagent 3-morpholinosydnonimine (SIN-1). The mitochondrial transmembrane potential (MTP), as measured using the dye JC-1, was rapidly decreased in immunostimulated or SIN-1-treated glial cells deprived of glucose. MnTMPyP, but not H2TMPyP, blocked the depolarization of MTP in those glial cells. The present data, at least in part, provide evidence for how glial cells die in the postischemic and/or recurrent ischemic brain. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)155-164
Number of pages10
JournalGLIA
Volume31
Issue number2
DOIs
Publication statusPublished - 2000

Keywords

  • Glia
  • Glucose deprivation
  • JC-1
  • Mitochondria
  • MnTMPyP

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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