title: PGC-1-related coactivator (PRC) negatively regulates endothelial adhesion of monocytes via inhibition of NF κB activity.
abstract: PGC-1-related coactivator (PRC) is a growth-regulated transcriptional cofactor known to activate many of the nuclear genes specifying mitochondrial respiratory function. Endothelial dysfunction is a prominent feature found in many inflammatory diseases. Adhesion molecules, such as VCAM-1, mediate the attachment of monocytes to endothelial cells, thereby playing an important role in endothelial inflammation. The effects of PRC in regards to endothelial inflammation remain unknown. In this study, our findings show that PRC can be inhibited by the inflammatory cytokine LPS in cultured human umbilical vein endothelial cells (HUVECs). In the presence of LPS, the expression of endothelial cell adhesion molecular, such as VCAM1 and E-selectin, is found to be increased. These effects can be negated by overexpression of PRC. Importantly, monocyte adhesion to endothelial cells caused by LPS is significantly attenuated by PRC. In addition, overexpression of PRC protects mitochondrial metabolic function and suppresses the rate of glycolysis against LPS. It is also found that overexpression of PRC decreases the transcriptional activity of NF-κB. These findings suggest that PRC is a negative regulator of endothelial inflammation.
authors: Intensive Care Unit of Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, China.
authors: Zhan
authors: Z
authors: Chengye
authors: Zhou
authors: Z
authors: Daixing
authors: Zhong
authors: Z
authors: Qiang
authors: Li
authors: L
authors: Shusheng
mesh_terms: D002448:Cell Adhesion; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000166:cytology*; D005786:Gene Expression Regulation; D006019:Glycolysis; D057809:HEK293 Cells; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007249:Inflammation; D008070:Lipopolysaccharides / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
chemical_list: D019040:E-Selectin; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1
keywords: Monocytes adhesion; NF-κB; PGC-1-related coactivator (PRC); Vascular inflammation