OBJECTIVE: A diverse range of lipid oxidation products detected in oxidized low-density lipoprotein (oxLDL) and atherosclerotic lesions are capable of eliciting biological responses in vascular cells. We performed DNA microarray experiments to explore novel responses of human umbilical vein endothelial cells (HUVECs) to oxLDL and its components. METHODS AND RESULTS: cDNA microarray analysis showed that oxLDL, lysophosphatidylcholine (LysoPC), 4-hydroxy-2-nonenal, and oxysterols altered gene expression specifically, but some genes were commonly induced in HUVECs. Solute carrier family 3 member 2 and family 7 member 5, encoding the heavy chain of the cell surface antigen 4F2 (4F2hc) and the L-type amino acid transporter 1 (LAT1), respectively, were induced by oxLDL and many oxidation products. LAT1 requires 4F2hc to form a heterodimeric functional complex to transport neutral amino acids into the cell. LysoPC increased membrane protein levels of LAT1 confirmed by Western blot analysis and also uptake of L-[(14)C]leucine, which was inhibited by a competitive inhibitor for LAT1. The release of interleukin 6 (IL-6) and IL-8 was increased in LysoPC-treated cells and was attenuated by the LAT1 inhibitor. CONCLUSIONS: These findings suggest that an increase in uptake of neutral amino acids induced by LysoPC results in enhancement of inflammatory responses of endothelial cells.
OBJECTIVE: A diverse range of lipid oxidation products detected in oxidized low-density lipoprotein (oxLDL) and atherosclerotic lesions are capable of eliciting biological responses in vascular cells. We performed DNA microarray experiments to explore novel responses of human umbilical vein endothelial cells (HUVECs) to oxLDL and its components. METHODS AND RESULTS: cDNA microarray analysis showed that oxLDL, lysophosphatidylcholine (LysoPC), 4-hydroxy-2-nonenal, and oxysterols altered gene expression specifically, but some genes were commonly induced in HUVECs. Solute carrier family 3 member 2 and family 7 member 5, encoding the heavy chain of the cell surface antigen 4F2 (4F2hc) and the L-type amino acid transporter 1 (LAT1), respectively, were induced by oxLDL and many oxidation products. LAT1 requires 4F2hc to form a heterodimeric functional complex to transport neutral amino acids into the cell. LysoPC increased membrane protein levels of LAT1 confirmed by Western blot analysis and also uptake of L-[(14)C]leucine, which was inhibited by a competitive inhibitor for LAT1. The release of interleukin 6 (IL-6) and IL-8 was increased in LysoPC-treated cells and was attenuated by the LAT1 inhibitor. CONCLUSIONS: These findings suggest that an increase in uptake of neutral amino acids induced by LysoPC results in enhancement of inflammatory responses of endothelial cells.
Authors: Longhou Fang; Richard Harkewicz; Karsten Hartvigsen; Philipp Wiesner; Soo-Ho Choi; Felicidad Almazan; Jennifer Pattison; Elena Deer; Tiffany Sayaphupha; Edward A Dennis; Joseph L Witztum; Sotirios Tsimikas; Yury I Miller Journal: J Biol Chem Date: 2010-08-14 Impact factor: 5.157
Authors: Chi Chen; Yatrik M Shah; Keiichirou Morimura; Kristopher W Krausz; Makoto Miyazaki; Terrilyn A Richardson; Edward T Morgan; James M Ntambi; Jeffrey R Idle; Frank J Gonzalez Journal: Cell Metab Date: 2008-02 Impact factor: 27.287
Authors: Gema Medina-Gomez; Sarah L Gray; Laxman Yetukuri; Kenju Shimomura; Sam Virtue; Mark Campbell; R Keira Curtis; Mercedes Jimenez-Linan; Margaret Blount; Giles S H Yeo; Miguel Lopez; Tuulikki Seppänen-Laakso; Frances M Ashcroft; Matej Oresic; Antonio Vidal-Puig Journal: PLoS Genet Date: 2007-04-27 Impact factor: 5.917