Erythropoietin production: evidence for multiple oxygen sensing pathways.

Abstract:

:The production of erythropoietin (Epo), the glycoprotein hormone which controls red blood cell formation, is regulated by feedback mechanisms sensing tissue oxygenation. The mechanism of the putative oxygen sensor has yet to be elucidated. There is evidence that at least two pathways participate in hypoxia signal transduction. One appears to involve a specific haem protein, and a second implicates reactive oxygen species (ROS). Iron catalyses the generation of intracellular ROS and therefore alters the cellular redox state. We have investigated the effect of modulating intracellular iron content on Epo production in Hep 3B cells. Iron chelation stimulates Epo production at 20% O2 and enhances Epo production at 1% O2, but it has no additive effect on cobalt-induced Epo production. Excess molar iron inhibited Epo production in response to hypoxia, desferrioxamine (DFO) and cobalt chloride and inhibited the DFO-enhancing effect of hypoxia-induced Epo production. We found that sulphydryl oxidising agents exert a differential inhibitory effect on hypoxia-induced versus DFO-induced Epo production, providing further evidence that multiple pathways of oxygen sensing exist.

journal_name

Ann Hematol

journal_title

Annals of hematology

authors

Daghman NA,Elder GE,Savage GA,Winter PC,Maxwell AP,Lappin TR

doi

10.1007/s002770050514

subject

Has Abstract

pub_date

1999-06-01 00:00:00

pages

275-8

issue

6

eissn

0939-5555

issn

1432-0584

journal_volume

78

pub_type

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