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:P43026 (
lipopolysaccharide
)
62,215
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Cytosolic proteins are required for regulation of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase (Nox) isozymes. Here we show that Src homology 3 (SH3) domain-containing YSC84-like 1 (
SH3YL1
), as a Nox4 cytosolic regulator, mediates
lipopolysaccharide
(
LPS
)-induced H
2
O
2
generation, leading to acute kidney injury. The
SH3YL1
, Ysc84p/Lsb4p, Lsb3p, and plant FYVE proteins (SYLF) region and SH3 domain of
SH3YL1
contribute to formation of a complex with Nox4-p22
phox
. Interaction of p22
phox
with
SH3YL1
is triggered by
LPS
, and the complex induces H
2
O
2
generation and pro-inflammatory cytokine expression in mouse tubular epithelial cells. After
LPS
injection,
SH3YL1
knockout mice show lower levels of acute kidney injury biomarkers, decreased secretion of pro-inflammatory cytokines, decreased infiltration of macrophages, and reduced tubular damage compared with wild-type (WT) mice. The results strongly suggest that
SH3YL1
is involved in renal failure in
LPS
-induced acute kidney injury (AKI) mice. We demonstrate that formation of a ternary complex of p22
phox
-
SH3YL1
-Nox4, leading to H
2
O
2
generation, induces severe renal failure in the
LPS
-induced AKI model.
...
PMID:LPS-Induced Acute Kidney Injury Is Mediated by Nox4-SH3YL1. 3308 58
