4-HNE inhibits tube formation and up-regulates chondromodulin-I in human endothelial cells.
The aim of the present study was to investigate the effects of 4-hydroxy-2-nonenal (4-HNE) on tube formation by human bone marrow endothelial cells (HBMEC). We found that 4-HNE at physiologically achievable concentrations (5 and 10 microM) inhibited the formation of tubes. Western blot analysis revealed that inhibition of tube formation by 4-HNE was associated with increased expression of chondromodulin-I (CHM-I), a protein with well-known anti-angiogenic properties. Cell viability assays showed that 4-HNE at concentrations of 10 microM or less did not cause HBMEC cell death. Luciferase reporter assays did not show any inducing effect of 4-HNE on the promoter activity of human CHM-I gene indicating that post-transcriptional or post-translational modifications may account for the up-regulation of CHM-I. Collectively, the results of the present study show for the first time that 4-HNE inhibits tube formation by HBMECs indicating a potential anti-angiogenic activity of 4-HNE. This inhibition occurs at least in part via 4-HNE-induced CHM-I protein expression.
Stagos
Dimitrios
D
Molecular Toxicology & Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado-Denver, 12700 E 19th Avenue, Aurora, CO 80045, USA.
Zhou
Hongfei
H
Ross
David
D
Vasiliou
Vasilis
V
D000447:Aldehydes / Q000494:pharmacology*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011401:Promoter Regions, Genetic / Q000187:drug effects; D015854:Up-Regulation
D000447:Aldehydes; D015853:Cysteine Proteinase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C068675:CNMD protein, human; C027576:4-hydroxy-2-nonenal