PMID- 19056352 OWN - NLM STAT- MEDLINE DCOM- 20090227 LR - 20211020 IS - 1090-2104 (Electronic) IS - 0006-291X (Print) IS - 0006-291X (Linking) VI - 379 IP - 3 DP - 2009 Feb 13 TI - 4-HNE inhibits tube formation and up-regulates chondromodulin-I in human endothelial cells. PG - 654-8 LID - 10.1016/j.bbrc.2008.11.095 [doi] AB - 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. FAU - Stagos, Dimitrios AU - Stagos D AD - Molecular Toxicology & Environmental Health Sciences Program, Department of Pharmaceutical Sciences, University of Colorado-Denver, 12700 E 19th Avenue, Aurora, CO 80045, USA. FAU - Zhou, Hongfei AU - Zhou H FAU - Ross, David AU - Ross D FAU - Vasiliou, Vasilis AU - Vasiliou V LA - eng GR - ES 09554/ES/NIEHS NIH HHS/United States GR - R29 EY011490/EY/NEI NIH HHS/United States GR - R01 EY011490/EY/NEI NIH HHS/United States GR - R01 EY011490-10/EY/NEI NIH HHS/United States GR - EY 11490/EY/NEI NIH HHS/United States GR - R01 ES009554-07/ES/NIEHS NIH HHS/United States GR - R01 ES009554/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20081203 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Aldehydes) RN - 0 (Cysteine Proteinase Inhibitors) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 0 (Membrane Proteins) RN - 136362-10-2 (CNMD protein, human) RN - K1CVM13F96 (4-hydroxy-2-nonenal) SB - IM MH - Aldehydes/*pharmacology MH - Bone Marrow Cells/*drug effects/metabolism MH - Cells, Cultured MH - Cysteine Proteinase Inhibitors/*pharmacology MH - Endothelial Cells/*drug effects/metabolism MH - Humans MH - Intercellular Signaling Peptides and Proteins/*biosynthesis/genetics MH - Membrane Proteins/*biosynthesis/genetics MH - Neovascularization, Physiologic/*drug effects MH - Promoter Regions, Genetic/drug effects MH - Up-Regulation PMC - PMC2757412 MID - NIHMS95188 EDAT- 2008/12/06 09:00 MHDA- 2009/02/28 09:00 PMCR- 2010/02/13 CRDT- 2008/12/06 09:00 PHST- 2008/11/19 00:00 [received] PHST- 2008/11/20 00:00 [accepted] PHST- 2008/12/06 09:00 [pubmed] PHST- 2009/02/28 09:00 [medline] PHST- 2008/12/06 09:00 [entrez] PHST- 2010/02/13 00:00 [pmc-release] AID - S0006-291X(08)02306-1 [pii] AID - 10.1016/j.bbrc.2008.11.095 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2009 Feb 13;379(3):654-8. doi: 10.1016/j.bbrc.2008.11.095. Epub 2008 Dec 3.