title: 17β-Estradiol regulates scavenger receptor class BI gene expression via protein kinase C in vascular endothelial cells.
abstract: High-density lipoprotein (HDL) mediates reverse cholesterol transport. In this process, the human homolog of the B class, type I scavenger receptor (SR-BI), CD36, and LIMPII analogous-1 (hSR-BI/CLA-1) facilitates the cellular uptake of cholesterol from HDL. In endothelial cells, HDL activates endothelial nitric oxide synthase (eNOS) via hSR-BI/CLA-1, and 17β-estradiol (E2) modulates nitric oxide (NO) synthesis. In this study, we elucidated the effect of E2 on hSR-BI/CLA-1 expression in human umbilical vein endothelial cells (HUVECs). HSR-BI/CLA-1 expression was examined by real-time PCR, western blot analysis and reporter gene assay in HUVECs incubated with E2. eNOS activity was assessed by detection of phosphorylation (Ser 1179) of eNOS. We investigated the effect of the constitutively active form or dominant negative form of protein kinase C on hSR-BI/CLA-1 promoter activity. Our results showed that E2 increased the endogenous expression of hSR-BI/CLA-1. E2 also enhanced the activity of the hSR-BI/CLA-1 promoter and the expression of its mRNA. However, bisindolylmaleimide I, an inhibitor of protein kinase C, blocked the stimulatory effect of E2 on hSR-BI/CLA-1 promoter activity. Moreover, constitutively active PKC increased the activity of the hSR-BI/CLA-1 promoter, and a dominant-negative mutant of PKC prevented E2 from stimulating promoter activity. In cells treated with E2, HDL stimulated the phosphorylation of serine 1179 of eNOS in HUVECs. These results suggested that E2 upregulates the expression of the endothelial hSR-BI/CLA-1 via the PKC pathway, which may be a novel mechanism of the anti-atherosclerotic potential of E2 in vascular endothelial cells.
authors.affiliation: Department of Advanced Medicine, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe Miki-cho, Kita-gun, Kagawa, 761-0793, Japan.
authors.forename: Youko
authors.initials: Y
authors.lastname: Fukata
authors.forename: Xiao
authors.initials: X
authors.lastname: Yu
authors.forename: Hitomi
authors.initials: H
authors.lastname: Imachi
authors.forename: Takamasa
authors.initials: T
authors.lastname: Nishiuchi
authors.forename: Jingya
authors.initials: J
authors.lastname: Lyu
authors.forename: Kayoko
authors.initials: K
authors.lastname: Seo
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takeuchi
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Iwama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Masugata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hoshikawa
authors.forename: Naohisa
authors.initials: N
authors.lastname: Hosomi
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Iwasaki
authors.forename: Koji
authors.initials: K
authors.lastname: Murao
mesh_terms: D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D004958:Estradiol; D052250:Nitric Oxide Synthase Type III; D011493:Protein Kinase C