Advanced glycation end products as an upstream molecule triggers ROS-induced sFlt-1 production in extravillous trophoblasts: a novel bridge between oxidative stress and preeclampsia

Autor: Min Zhang, Qi-tao Huang, Li-lin Hang, Yun-fei Gao, Mei Zhong, Y.H. Yu, Liping Huang, Zhijian Wang, W.Z. Liang
Rok vydání: 2013
Předmět:
Placental growth factor
Glycation End Products
Advanced
Vascular Endothelial Growth Factor A
medicine.medical_specialty
Pregnancy Proteins
RAGE (receptor)
Cell Line
chemistry.chemical_compound
Pre-Eclampsia
Glycation
Pregnancy
Internal medicine
medicine
Humans
Molecular Targeted Therapy
RNA
Messenger
Enzyme Inhibitors
Placenta Growth Factor
NADPH oxidase
Vascular Endothelial Growth Factor Receptor-1
biology
Obstetrics and Gynecology
Acetophenones
Gene Expression Regulation
Developmental
NADPH Oxidases
Serum Albumin
Bovine
Polycystic ovary
Cell biology
Trophoblasts
Up-Regulation
Vascular endothelial growth factor
Oxidative Stress
Endocrinology
Reproductive Medicine
chemistry
Immunoglobulin G
embryonic structures
Apocynin
biology.protein
Female
Reactive Oxygen Species
Soluble fms-like tyrosine kinase-1
Developmental Biology
Zdroj: Placenta. 34(12)
ISSN: 1532-3102
Popis: Although abnormal soluble fms-like tyrosine kinase-1 (sFlt-1) production is thought to be an important factor in the pathogenesis of pre-eclampsia, the mechanisms that regulate the production of sFlt-1 during pre-eclampsia are unclear. Accumulation of advanced glycation end products (AGEs) is prevalent in obesity, advanced maternal age, diabetes mellitus, and polycystic ovary syndrome. Alterations in the regulation and signaling of angiogenic pathways have been considered as a link between these conditions and pre-eclampsia. The purpose of this study was to explore the possible effects of AGEs on sFlt-1 secretion in extravillous trophoblasts (EVT). A EVT cell line (HRT-8/SVneo) was treated with various concentrations of AGEs-BSA. The mRNA expression of sFlt-1, vascular endothelial growth factor (VEGF), and placental growth factor (PlGF) in EVT were detected with real-time polymerase chain reaction. The secretion of sFlt-1, VEGF, and PlGF protein from EVT was measured with ELISA. The levels of intracellular reactive oxygen species (ROS) production were determined by DCFH-DA. Exposure of EVT to AGEs-BSA induced increased intracellular ROS generation and overexpression of sFlt-1 at mRNA and protein levels in a dose dependent manner. Anti-RAGE immunoglobulin G or apocynin (an inhibitors of NADPH oxidase) could decrease the intracellular ROS generation and subsequently suppressed the production of sFlt-1 at mRNA and protein levels. Our data suggested that AGEs may be a new class of important mediator in the regulation of angiogenic pathways of EVT. Accumulation of AGEs might contribute to the pathogenesis of preeclampsia by promoting sFlt-1 production through activation of RAGE/NADPH oxidase dependent pathway in EVT.
Databáze: OpenAIRE
Externí odkaz: