Biology Reference
In-Depth Information
Another example of a pathogenic protozoan lacking globins is
T. brucei
(Supplementary Table S1 at
http://www.elsevierdirect.com/companions/
9780124076938
)
, the causal agent of sleeping sickness. Again, the innate
response against trypanosomes involves the production of NO by iNOS
(
Gobert et al., 2000
), playing an essential role as a messenger between
trypanosomes and the host immune and nervous system (
Antoine-
Moussiaux, Magez, & Desmecht, 2008
). However, in an infected mice
model, proliferation of trypanosomes in the proximity of peripheral macro-
phages was associated with decreased NO-dependent cytotoxicity. Indeed,
NO levels are decreased in the blood of animals infected with
T.
(
brucei
)
brucei
(
Buguet, Banzet, Bouteille, Vincendeau, & Tapie, 2002; Buguet
et al., 1996
). The requirement for a common substrate,
L
-arginine, for
both arginase and iNOS reduces NO production and favours synthesis of
polyamines, compounds required for trypanosome development
(
Amrouni et al., 2010; Duleu et al., 2004
). On the other hand, in the
brain, NO concentrations are increased, due perhaps to the presence
of iNOS in glial and neuron cells (
Amrouni et al., 2010
). Utilization of
L
-arginine might be an indirect protection mechanism. However, how
this organism deals with the toxicity of NO in the brain is not clear.
NOS activity has been discovered also in
Trypanosoma cruzi
(
Paveto et al.,
1995
) and
Leishmania donovani
(
Basu, Kole, Ghosh, & Das, 1997
). None
of them contains globins.
www.elsevierdirect.com/companions/9780124076938
possess one or
more FHbs.
D
.
discoideum
possesses two (
Iijima et al., 2000
). This chapter
draws the surprising conclusion that, for FHbs in general, 'their physiolog-
ical significance has not yet been determined', despite a large body of evi-
dence predating 2000 showing their key role in NO detoxification. The two
D
.
discoideoum
globin genes (
DdFHa
and
DdFHb
) are in close proximity on
the chromosome. Their expression was induced by submerged culture con-
ditions. Simultaneous disruption of both genes, but not of the genes individ-
ually, led to a striking sensitivity to GSNO and sodium nitroprusside. These
are not effective NO-releasing molecules but the growth sensitivity to these
compounds does suggest a role for the globins in nitrosative stress tolerance.
Paraquat and hydrogen peroxide were not effective in reducing viability of
the mutants.
A functional FHb is encoded by the genome of
G. lamblia
(Excavata), a
mammalian parasite of the small intestine (
Rafferty, Luu, March, & Yee,
