Rat carotid body chemosensory discharge and glomus cell HIF-1 alpha expression in vitro: regulation by a common oxygen sensor.
Addition of Pco ( approximately 350 Torr) to a normoxic medium (Po(2) of approximately 130 Torr) was used to investigate the relationship between carotid body (CB) sensory discharge and expression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) in glomus cells. Afferent electrical activity measured for in vitro-perfused rat CB increased rapidly (1-2 s) with addition of high CO (Pco of approximately 350 Torr; Po(2) of approximately 130 Torr), and this increase was fully reversed by white light. At submaximal light intensities, the extent of reversal was much greater for monochromatic light at 430 and 590 nm than for light at 450, 550, and 610 nm. This wavelength dependence is consistent with the action spectrum of the CO compound of mitochondrial cytochrome a(3). Interestingly, when isolated glomus cells cultured for 45 min in the presence of high CO (Pco of approximately 350 Torr; Po(2) of approximately 130 Torr) in the dark, the levels of HIF-1 alpha, which turn over slowly (many minutes), increased. This increase was not observed if the cells were illuminated with white light during the incubation. Monochromatic light at 430- and 590-nm light was much more effective than that at 450, 550, and 610 nm in blocking the CO-induced increase in HIF-1 alpha, as was the case for chemoreceptor discharge. Although the changes in HIF-1 alpha take minutes and those for CB neural activity occur in 1-2 s, the similar responses to CO and light suggest that the oxygen sensor is the same (mitochondrial cytochrome a(3)).
Roy
Arijit
A
Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6059, USA.
Baby
Santhosh M
SM
Wilson
David F
DF
Lahiri
Sukhamay
S
D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism / Q000494:pharmacology; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D045266:Cytochromes a3 / Q000378:metabolism; D003624:Darkness; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D066298:In Vitro Techniques; D008029:Lighting; D008297:Male; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism* / Q000494:pharmacology; D010313:Partial Pressure; D051381:Rats
D045266:Cytochromes a3; C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D002248:Carbon Monoxide; D010100:Oxygen