RRC ID 78573
Author Yamamoto H, Tanaka Y, Sawada M, Kihara S.
Title ERRα Attenuates Vascular Inflammation via Enhanced NFκB Degradation Pathway.
Journal Endocrinology
Abstract We have previously reported that β-aminoisobutyric acid (BAIBA), a muscle-derived exercise mimetic, had anti-inflammatory and reactive oxygen species (ROS) scavenging effects in vascular endothelial cells through the enhanced expression of peroxisome proliferator-activated receptor gamma coactivator-1β (PGC-1β). Although BAIBA also increased the expression of estrogen-related receptor α (ERRα), the roles of ERRα in vascular endothelial cells have yet to be fully elucidated. Here, we found that human aortic endothelial cells (HAECs) infected with ERRα-expressing adenovirus had significantly decreased mRNA levels of tumor necrosis factor α-stimulated proinflammatory molecules. However, ERRα overexpression had little effect on the mRNA levels of PGC-1β, peroxisome proliferator-activated receptors, and almost all ROS scavenging molecules, except for superoxide dismutase 2. ERRα expression significantly decreased NFκB reporter activities in a dose-dependent manner with unaltered IκBα phosphorylation levels but with a significant increase in the mRNA levels of PDZ and LIM domain protein 2 (PDLIM2) and copper metabolism gene MURR1 domain-containing protein (COMMD1), which enhance the ubiquitination and degradation of NFκB. Also, PDLIM2 and COMMD1 mRNA levels were upregulated in BAIBA-treated HAECs. Finally, we identified the ERRα-response element in the COMMD1 promoter region (-283 to -29 bp). These results indicated that ERRα exerted anti-inflammatory effects in vascular endothelial cells through COMMD1-mediated attenuation of NFκB activity, which could be an atheroprotective mechanism of physical exercise.
Volume 164(3)
Published 2023-1-9
DOI 10.1210/endocr/bqac212
PII 6936569
PMID 36534970
MeSH ERRalpha Estrogen-Related Receptor Endothelial Cells* / metabolism Humans Inflammation LIM Domain Proteins / metabolism Microfilament Proteins / metabolism NF-kappa B / metabolism Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / metabolism RNA, Messenger Reactive Oxygen Species / metabolism Receptors, Estrogen / genetics Receptors, Estrogen / metabolism Transcription Factors* / metabolism
Human and Animal Cells 293(RCB1637)