Phenazine methosulfate decreases HIF-1α accumulation during the exposure of cells to hypoxia.
Biosci Biotechnol Biochem
; 76(9): 1682-7, 2012.
Article
in En
| MEDLINE
| ID: mdl-23006579
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.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oxygen
/
Signal Transduction
/
Protein Processing, Post-Translational
/
Oxidants
/
Hypoxia-Inducible Factor 1, alpha Subunit
/
Methylphenazonium Methosulfate
Limits:
Humans
Language:
En
Journal:
Biosci Biotechnol Biochem
Journal subject:
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2012
Document type:
Article
Affiliation country:
Japan