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: UMLS:C0268318 (
ICP
)
10,007
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Intrahepatic cholestasis of pregnancy
(
ICP
) is a pregnancy-specific disorder characterised by raised bile acids in foetal-maternal circulation, which threatens perinatal health. During the progression of
ICP
, the effect of oxidative stress is underscored.
Peroxiredoxin-3
(
PRDX3
) is a mitochondrial antioxidant enzyme that is crucial to balance intracellular oxidative stress. However, the role of
PRDX3
in placental trophoblast cells under
ICP
is not fully understood. We demonstrated that the level of
PRDX3
was downregulated in
ICP
placentas as well as bile acids-treated trophoblast cells and villous explant in vitro. Toxic levels of bile acids and
PRDX3
knockdown induced oxidative stress and mitochondrial dysfunction in trophoblast cells. Moreover, silencing of
PRDX3
in trophoblast cell line HTR8/SVneo induced growth arrest and cellular senescence via activation of p38-mitogen-activated protein kinase (MAPK) and induction of p21
WAF1/CIP
and p16
INK4A
. Additionally, enhanced cellular senescence, determined by senescence-associated beta-galactosidase staining, was obviously attenuated by p38-MAPK inhibitor SB203580. Our data determined that exposure to bile acid decreased
PRDX3
level in human trophoblasts.
PRDX3
protected trophoblast cells against mitochondrial dysfunction and cellular senescence induced by oxidative stress. Our results suggest that decreased
PRDX3
by excessive bile acids in trophoblasts plays a critical role in the pathogenesis and progression of
ICP
.
...
PMID:Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts. 2795 41
