Activation of HIF-1alpha mRNA by hypoxia and iron chelator in isolated rat carotid body.
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).
Roy
Arijit
A
Department of Physiology, School of Medicine, University of Pennsylvania, B-400 Richards Building, 3700 Hamilton Walk, Philadelphia, PA 19104-6085, USA.
Volgin
Denys V
DV
Baby
Santhosh M
SM
Mokashi
Anil
A
Kubin
Leszek
L
Lahiri
Sukhamay
S
D000818:Animals; D002344:Carotid Body / Q000187:drug effects* / Q000378:metabolism; D000077768:Ciclopirox; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011728:Pyridones / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007502:Iron Chelating Agents; D011728:Pyridones; D012333:RNA, Messenger; D014157:Transcription Factors; D000077768:Ciclopirox; D010100:Oxygen