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Phenazine methosulfate decreases HIF-1α accumulation during the exposure of cells to hypoxia.

Abstract
In HEK293 cells, exposure to various NAD(P)H oxidants, including phenazine methosulfate (PMS), that non-enzymatically oxidize intracellular NAD(P)H to NAD(P), decreased hypoxia-induced hypoxia-inducible factor 1 (HIF-1α) accumulation. RT-PCR and cycloheximide inhibition experiments indicated that PMS-induced HIF-1α decrease is involved in post-translational degradation during hypoxia. The decrease in HIF-1α caused by PMS was not eliminated by proteasome inhibitor MG132. Moreover, the increase in HIF-1α induced by exposure to MG132 alone in normoxia was diminished by PMS. In contrast, calpastatin peptide, a calpain inhibitor, fully prevented PMS-induced reduction in HIF-1α in hypoxic cells. These data suggest that the decreased stability of HIF-1α induced by PMS is due to the activation by PMS of a protein degradation system that is independent of the ubiquitin-proteasome pathway.
AuthorsAkiko Yamaki, Haruhiro Muratsubaki
JournalBioscience, biotechnology, and biochemistry (Biosci Biotechnol Biochem) Vol. 76 Issue 9 Pg. 1682-7 ( 2012) ISSN: 1347-6947 [Electronic] England
PMID23006579 (Publication Type: Journal Article)
Chemical References
  • Calcium-Binding Proteins
  • Cysteine Proteinase Inhibitors
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Leupeptins
  • Oxidants
  • Proteasome Inhibitors
  • Protein Synthesis Inhibitors
  • Methylphenazonium Methosulfate
  • calpastatin
  • Cycloheximide
  • Proteasome Endopeptidase Complex
  • benzyloxycarbonylleucyl-leucyl-leucine aldehyde
  • Oxygen
Topics
  • Calcium-Binding Proteins (pharmacology)
  • Cell Hypoxia
  • Cycloheximide (pharmacology)
  • Cysteine Proteinase Inhibitors (pharmacology)
  • HEK293 Cells
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
  • Leupeptins (pharmacology)
  • Methylphenazonium Methosulfate (pharmacology)
  • Oxidants (pharmacology)
  • Oxygen (pharmacology)
  • Proteasome Endopeptidase Complex (metabolism)
  • Proteasome Inhibitors (pharmacology)
  • Protein Processing, Post-Translational (drug effects)
  • Protein Stability (drug effects)
  • Protein Synthesis Inhibitors (pharmacology)
  • Proteolysis (drug effects)
  • Signal Transduction (drug effects, genetics)

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