Possible involvement of pyruvate kinase in acquisition of tolerance to hypoxic stress in glial cells

Takahiro Shimizu, Takashi Uehara, Yasuyuki Nomura

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Neurons are highly vulnerable to ischemic/hypoxic stress, while glial cells show tolerance to such stress. However, the mechanisms for tolerance acquisition in glial cells have yet to be established. We attempted to isolate and identify a stress protein that is upregulated in response to hypoxia in human astrocytoma CCF-STTG1 cells. In particular, pyruvate kinase (PK) was upregulated by hypoxia in CCF-STTG1 cells. Hypoxia-inducible factor 1 (HIF-1), the primary transcription factor that is responsible for multiple gene activation under hypoxia, plays a critical role in PK expression during hypoxic challenge. To determine whether newly synthesized PK is involved in tolerance to hypoxic stress, we established the PK-overexpressing neuronal cells. Overexpression of the wild-type, but not the kinase-negative mutant, resulted in attenuation of the loss of cell viability and the typical apoptotic features by hypoxia or oxidative stress in SK-N-MC cells. These findings suggest that upregulation of PK may result in acquisition of tolerance against hypoxic stress, and that the antioxidant effect may be involved in the protective effect of PK.

Original languageEnglish
Pages (from-to)167-175
Number of pages9
JournalJournal of Neurochemistry
Volume91
Issue number1
DOIs
Publication statusPublished - Oct 1 2004
Externally publishedYes

Keywords

  • Brain ischemia
  • Glial cells
  • Hypoxia
  • Hypoxia-inducible factor 1
  • Pyruvate kinase
  • Stress tolerance

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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