摘要: Oxysterol binding to liver X receptors (LXR) increases the transcription of genes involved in cholesterol efflux and disposal, such as ABCA1 (ATP-binding cassette transporter A1). Other cytoplasmic sterol-binding proteins could interact with this pathway by sequestering or delivering substrates ligands. One potential regulator is OSBP (oxysterol-binding protein), which implicated integration sterol sensing/transport sphingomyelin synthesis cell signaling. Since these activities impact pathway, we examined whether was LXR regulation expression activity ABCA1. Suppression Chinese hamster ovary cells RNA interference resulted increased protein following induction oxysterols synthetic agonist TO901317. knockdown J774 macrophages also presence absence agonists. depletion did not affect mRNA levels activity. Rather, silencing half-life 3-fold. Sphingomyelin suppressed OSBP-depleted treated 25-hydroxycholesterol but TO901317 22-hydroxycholesterol correlate stabilization. Moreover, co-transfection experiments revealed that reduction prevented a mutation domain mutations abrogated interaction Golgi apparatus endoplasmic reticulum. Thus, opposes negatively regulating cytoplasm domain-dependent destabilization.
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