|
| |
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online September 15, 2004
Journal of Experimental Biology 207, v (2004)
Copyright © 2004 The Company of Biologists Limited
doi: 10.1242/jeb.01247
Outside JEB |
BLIND AGAINST HYPOXIA STRESS
University of California at Davis
ltomanek{at}ucdavis.edu
|
Living in underground borrows, Spalax, the blind subterranean mole
rat, is often exposed to extreme fluctuations of oxygen level due to changes
in the soil's gas permeability caused by seasonal floods that saturate the
soil. As a result of their subterranean life-style, Spalax belong to
the group of mammals with the greatest degree of hypoxia tolerance. Intrigued
by the animal's remarkable hypoxia tolerance, Imad Shams and colleagues from
University of Haifa in Israel decided to focus on the expression of two key
indicators of hypoxic stress, erythropoietin (Epo) and
hypoxia-inducible factor 1
(HIF-1) to assess the
animals' hypoxia tolerance.
HIF1 is a transcription factor that responds rapidly to periods of hypoxia.
Under normoxic conditions, one of the HIF1 components, HIF-1, is
constantly broken down, and so HIF1 is unable to activate hypoxia-induced
genes. However, under hypoxic conditions, the HIF-1 component is
stabilised, and HIF-1 can in turn bind to an enhancer element in
hypoxia-induced genes, such as the Epo gene, and activate its
transcription; HIF-1 levels are said to be post-translationally
regulated. Epo's main, but not its only, function is the regulation of levels
of red blood cells. Knowing that the kidney is the main site of Epo
production, Shams and coworkers compared Epo mRNA expression levels
in the kidneys of white rats and several species of mole rats,
Spalax, and found that Epo expression increased more in the
hypoxia tolerant subterranean mole rats than in white rats at low oxygen
levels. But when they looked at a time course of Epo expression in
subterranean mole rat, they were in for a surprise! Although Epo
levels increased dramatically over the first 24 h of hypoxia, its expression
returned close to normoxic levels after 44 h. Differences between Epo
expression were not only found between white and mole rats, but also between
different species of Spalax in extreme hypoxic conditions, with
animals from damp hypoxic burrows producing higher levels of Epo than
animals from well oxygenated burrows. Interestingly, the time course and the
fact that the development of erythrocytes takes up to 2 weeks suggests that
Epo may have other functions than erythropoiesis in setting hypoxia tolerance
limits in Spalax.
Investigating the levels of HIF-1, the team found that
under normal conditions, hypoxia-tolerant blind subterranean mole rats
naturally produced twice as much HIF-1 mRNA as
hypoxia-sensitive white rats. And when they dropped the oxygen levels to only
3%, blind mole rat's HIF-1 mRNA levels rose dramatically,
peaking after 4 h, while the HIF-1 levels of rats exposed to
low levels of oxygen didn't change from their normoxic levels. Given that
HIF-1 levels are normally regulated at the protein level, the team was
surprised to see that the blind subterranean mole rats seemed able to regulate
the levels of HIF-1 mRNA, making them suspect that the
HIF-1 gene itself might also be regulated by hypoxia.
Next the team compared the HIF-1 levels of two different
species of blind mole rats, from flooded and well-aerated areas, and found
that the animals from the wetter and more hypoxic environment had higher
levels of HIF-1 than the animals from well-aerated burrows.
Shams suggests that `this pattern of Epo and HIF-1
expression is a substantial contribution to the adaptive strategy of hypoxia
tolerance in Spalax'.
Having identified that HIF-1 and Epo are probably
major players in the rodents' remarkable hypoxia tolerance, Shams and
colleagues are keen to know whether the mRNA and protein levels of
HIF-1 respond to fluctuating oxygen levels, given that blind
mole rats survive such large fluctuations in oxygen level; hopefully making us
less blind towards the promising lessons we can learn from an odd mammal
living underground.
References
Shams, I., Avivi, A. and Nevo, E. (2004).
Hypoxic stress tolerance of the blind subterranean mole rat: Expression of
erythropoietin and hypoxia-inducible factor 1. Proc. Natl.
Acad. Sci. USA 101,9698
-9703.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||
