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- Title
Lysophosphatidylcholine promotes SREBP-2 activation via rapid cholesterol efflux and SREBP-2-independent cytokine release in human endothelial cells.
- Authors
Mayuko Morita; Azusa Sekine; Yasuomi Urano; Taki Nishimura; Wakako Takabe; Hiroyuki Arai; Takao Hamakubo; Tatsuhiko Kodama; Noriko Noguchi
- Abstract
Lysophosphatidylcholine (LPC) and oxysterols which are major components in oxidized low-density lipoprotein have been shown to possess an opposite effect on the expression of sterol regulatory element-binding protein- 2 (SREBP-2) target genes in endothelial cells. In this study, we aimed at elucidating the mechanisms of activation of SREBP-2 by LPC and evaluating the effects of LPC and 25-hydroxycholesterol (25-HC) on the release of inflammatory cytokines. Human umbilical vein endothelial cells were treated with LPC or oxysterols including 25-HC. LPC activated SREBP-2 within 15 min, resulting in induction of expression of SREBP-2 target genes which were involved in intracellular cholesterol homeostasis. The rapid activation of SREBP-2 was caused by enhanced efflux of intracellular cholesterol, which was evaluated using 14C-acetate. The LPC-induced activation of SREBP-2 was inhibited by addition of 25-HC. In contrast, both LPC and 25-HC increased release of interleukin-6 (IL-6) and IL-8, respectively and additively. In conclusion, LPC activated SREBP-2 via enhancement of cholesterol efflux, which was suppressed by 25-HC. The release of inflammatory cytokines such as IL-6 and IL-8 in endothelial cells was SREBP-2-independent. LPC and 25-HC may act competitively in cholesterol homeostasis but additively in inflammatory cytokine release.
- Subjects
LYSOPHOSPHATIDYLCHOLINE acyltransferase; CHOLESTEROL; OXYSTEROLS; STEROLS; CYTOKINES; ENDOTHELIAL cells
- Publication
Journal of Biochemistry, 2015, Vol 158, Issue 4, p331
- ISSN
0021-924X
- Publication type
Article
- DOI
10.1093/jb/mvv044