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: UNIPROT:P00750 (
PLA
)
16,800
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Eicosanoids mediate both cellular and humoral immune responses in insects. Phospholipase A
2
(
PLA
2
) catalyzes the first committed step in eicosanoid biosynthesis. It is a common pathogenic target of two entomopathogenic bacteria,
Xenorhabdus
and
Photorhabdus
. The objective of this study was to identify novel
PLA
2
inhibitors from
X. hominickii
and determine their immunosuppressive activities. To identify novel
PLA
2
inhibitors, stepwise fractionation of
X. hominickii
culture broth and subsequent enzyme assays were performed. Eight purified fractions of bacterial metabolites were obtained. Gas chromatography and mass spectrometry (GC-MS) analysis predicted that the main components in these eight fractions were 2-cyanobenzoic acid, dibutylamine, 2-ethyl 1-hexanol, phthalimide (PM), dioctyl terephthalate,
docosane
, bis (2-ethylhexyl) phthalate, and 3-ethoxy-4-methoxyphenol (EMP). Their synthetic compounds inhibited the activity of
PLA
2
in hemocytes of a lepidopteran insect,
Spodoptera exigua
, in a dose-dependent manner. They also showed significant inhibitory activities against immune responses such as prophenoloxidase activation and hemocytic nodulation of
S. exigua
larvae, with PM and EMP exhibiting the most potent inhibitory activities. These immunosuppressive activities were specific through
PLA
2
inhibition because an addition of arachidonic acid, a catalytic product of
PLA
2
, significantly rescued such suppressed immune responses. The two most potent compounds (PM and EMP) showed significant insecticidal activities after oral administration. When the compounds were mixed with
Bacillus thuringiensis
(Bt), they markedly increased Bt pathogenicity. This study identified eight
PLA
2
inhibitors from bacterial metabolites of
X. hominickii
and demonstrated their potential as novel insecticides.
...
PMID:Immunosuppressive Activities of Novel PLA
2
Inhibitors from
Xenorhabdus hominickii
, an Entomopathogenic Bacterium. 3275 64
