Activation of HIF-1alpha mRNA by hypoxia and iron chelator in isolated rat carotid body

Neurosci Lett. 2004 Jun 17;363(3):229-32. doi: 10.1016/j.neulet.2004.03.073.

Abstract

The hypoxia inducible factor-1alpha (HIF-1alpha) protein level is increased by hypoxia and iron chelator (ciclopirox olamine) in isolated rat carotid body (CB) and glomus cells. Reverse transcription and polymerase chain reaction (RT-PCR) are performed to test whether this increase is caused, at least in part, by increased HIF-1alpha gene transcription. HIF-1alpha mRNA levels dose-dependently increased and decreased in the rat CBs incubated for 1 h in a medium saturated with O(2) levels that were varied around nominally normoxic level of 21% in the 0-95% range. The iron chelator, ciclopirox olamine (5 microM), stimulated HIF-1alpha mRNA production under normoxic condition. Thus, in the CB, the main systemic O(2)-sensing organ, HIF-1alpha transcription is regulated by O(2) supply around the normoxic level; this may contribute to cellular and organismal adaptations to chronic changes in ambient O(2).

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Carotid Body / drug effects*
  • Carotid Body / metabolism
  • Ciclopirox
  • Dose-Response Relationship, Drug
  • Gene Expression Regulation / drug effects
  • Hypoxia / genetics
  • Hypoxia / metabolism*
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • In Vitro Techniques
  • Iron Chelating Agents / pharmacology*
  • Male
  • Oxygen / metabolism*
  • Pyridones / pharmacology
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction / methods
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Iron Chelating Agents
  • Pyridones
  • RNA, Messenger
  • Transcription Factors
  • Ciclopirox
  • Oxygen