Up-regulation of protein-disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death

Shinji Tanaka, Takashi Uehara, Yasuyuki Nomura

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

We isolated and identified a stress protein that is upregulated in response to hypoxia in primary-cultured glial cells. Protein-disulfide isomerase (PDI) was up-regulated not only by hypoxia in glia in vitro, but also by transient forebrain ischemia in rats in vivo. To determine whether newly synthesized PDI is involved in tolerance to ischemic stress, we carried out two procedures to induce PDI gene expression in human neuroblastoma SK-N- MC cells, as well as intrahippocampal injection following electroporation of an expression vector capable of overexpressing PDI in rats. Overexpression of this gene resulted in attenuation of the loss of cell viability induced by hypoxia in neuroblastoma SK-N-MC cells and a reduction in the number of DNA- fragmented cells in the CA1 area of the hippocampus in brain ischemic rats, respectively. These findings suggest that up-regulated PDI may play a critical role in resistance to ischemic damage, and that the elevation of levels of this protein in the brain may have beneficial effects against brain stroke.

Original languageEnglish
Pages (from-to)10388-10393
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number14
DOIs
Publication statusPublished - Apr 7 2000
Externally publishedYes

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Protein Disulfide-Isomerases
Brain Hypoxia-Ischemia
Cell death
Brain
Cell Death
Up-Regulation
Rats
Neuroblastoma
Neuroglia
Electroporation
Prosencephalon
Heat-Shock Proteins
Gene expression
Cultured Cells
Hippocampus
Cell Survival
Ischemia
Genes
Stroke
Cells

ASJC Scopus subject areas

  • Biochemistry

Cite this

Up-regulation of protein-disulfide isomerase in response to hypoxia/brain ischemia and its protective effect against apoptotic cell death. / Tanaka, Shinji; Uehara, Takashi; Nomura, Yasuyuki.

In: Journal of Biological Chemistry, Vol. 275, No. 14, 07.04.2000, p. 10388-10393.

Research output: Contribution to journalArticle

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