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:2.5.1.18 (
glutathione S-transferase
)
22,582
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Voltage-gated sodium (Na
v
) channels play a central role in the generation and propagation of action potentials in excitable cells such as neurons and muscles. To determine how the phenotypes of Na
v
-channel mutants are affected by other genes, we performed a forward genetic screen for dominant modifiers of the seizure-prone, gain-of-function
Dr
osophila melanogaster
Na
v
-channel mutant,
para
Shu
Our analyses using chromosome deficiencies, gene-specific RNA interference, and single-gene mutants revealed that a null allele of
glutathione S-transferase
S1
(
GstS1
) dominantly suppresses
para
Shu
phenotypes. Reduced
GstS1
function also suppressed phenotypes of other seizure-prone Na
v
-channel mutants,
para
GEFS+
and
para
bss
Notably,
para
Shu
mutants expressed 50% less
GstS1
than wild-type flies, further supporting the notion that
para
Shu
and
GstS1
interact functionally. Introduction of a loss-of-function
GstS1
mutation into a
para
Shu
background led to up- and down-regulation of various genes, with those encoding cytochrome P450 (CYP) enzymes most significantly over-represented in this group. Because
GstS1
is a fly ortholog of mammalian hematopoietic prostaglandin D synthase, and in mammals CYPs are involved in the oxygenation of polyunsaturated fatty acids including prostaglandins, our results raise the intriguing possibility that bioactive lipids play a role in
GstS1
-mediated suppression of
para
Shu
phenotypes.
...
PMID:Reduced Function of the Glutathione S-Transferase S1 Suppresses Behavioral Hyperexcitability in
Drosophila
Expressing Mutant Voltage-Gated Sodium Channels. 3205 35
