Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:4.6.1.2 (
guanylate cyclase
)
8,497
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Neuroglobin is a newly identified vertebrate globin that binds O(2) and is expressed in cerebral neurons. We found recently that neuronal expression of
neuroglobin
is stimulated by hypoxia and ischemia and protects neurons from hypoxic injury. Here we report that, like hemoglobin and myoglobin,
neuroglobin
expression can also be induced by hemin. Induction was concentration dependent and time dependent, with maximal (about 4-fold) increases in
neuroglobin
mRNA and protein levels occurring with 50 microM hemin and at 8 to 24 hours. The inductive effect of hemin was attenuated by the protein kinase G inhibitor KT5823 and the soluble
guanylate cyclase
inhibitor LY83583, was mimicked by treatment with 8-bromo-cyclic guanosine 3',5'-monophosphate, and was accompanied by a greater than 10-fold increase in cGMP levels, suggesting that it is mediated through protein kinase G and soluble
guanylate cyclase
. In contrast, hypoxic induction of
neuroglobin
was blocked by the mitogen-activated protein kinase/extracellular signal-regulated kinase kinase inhibitor PD98059, indicating that hemin and hypoxia regulate
neuroglobin
expression by different mechanisms. These results provide evidence for regulation of
neuroglobin
expression by at least 2 signal transduction pathways.
...
PMID:Hemin induces neuroglobin expression in neural cells. 1223 61
Sensory receptor neurons match their dynamic range to ecologically relevant stimulus intensities. How this tuning is achieved is poorly understood in most receptors. The roundworm
Caenorhabditis elegans
avoids 21% O
2
and hypoxia and prefers intermediate O
2
concentrations. We show how this O
2
preference is sculpted by the antagonistic action of a
neuroglobin
and an O
2
-binding soluble
guanylate cyclase
. These putative molecular O
2
sensors confer a sigmoidal O
2
response curve in the URX neurons that has highest slope between 15 and 19% O
2
and approaches saturation when O
2
reaches 21%. In the absence of the
neuroglobin
, the response curve is shifted to lower O
2
values and approaches saturation at 14% O
2
In behavioral terms,
neuroglobin
signaling broadens the O
2
preference of
Caenorhabditis elegans
while maintaining avoidance of 21% O
2
A computational model of aerotaxis suggests the relationship between GLB-5-modulated URX responses and reversal behavior is sufficient to broaden O
2
preference. In summary, we show that a
neuroglobin
can shift neural information coding leading to altered behavior. Antagonistically acting molecular sensors may represent a common mechanism to sharpen tuning of sensory neurons.
...
PMID:Modulation of sensory information processing by a neuroglobin in
Caenorhabditis elegans
. 2853
