Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 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 p21WAF1/CIP and p16INK4A. 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.
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PMID:Downregulation of peroxiredoxin-3 by hydrophobic bile acid induces mitochondrial dysfunction and cellular senescence in human trophoblasts. 2795 41

This study aims to explore the effect of p38 mitogen-activated protein kinase and its downstream target HMG-box transcription factor 1 (HBP1) in the chondrocyte (CH) senescence caused by hyperosmotic stress. Human cartilage tissue with or without osteoarthritis (OA) were collected to detect the differential expression of p38 and HBP1 by Western blot. CHs were isolated from cartilage without OA and used the hyperosmotic medium to accelerate CH senescence in vitro. A p38 inhibitor and siRNA were used to mediate the expression of p38 and HBP1. The viability of CHs was determined by cell counting kit 8 (CCK8) assay. CH-related mRNA expression was analyzed by quantitative real-time polymerase chain reaction (RT-PCR). Immunofluorescence was also used to detect collagen II and beta-galactosidase expression. Senescent cells were increased in both OA cartilage and hyperosmotic stress treatment with a marked upregulation of p38 and HBP1. Suppression of p38 activation reversed the hyperosmotic stress-induced CH senescence and led to an inhibition of HBP1, p16, Runx-2, MMP-13, collagen X expression, and an upregulation of collagen II and SOX-9 expression. Moreover, the silencing of HBP1 also played a protective effect on CH senescence. The suppression of the p38/HBP1 pathway alleviates the hyperosmotic stress-induced senescent progression of CHs.
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PMID:Suppression of p38/HBP1 pathway alleviates hyperosmotic stress-induced senescent progression of chondrocyte senescence. 3254 82


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