کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5945547 1172352 2014 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
3β,5α,6β-Cholestanetriol and 25-hydroxycholesterol accumulate in ATP-binding cassette transporter G1 (ABCG1)-deficiency
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
3β,5α,6β-Cholestanetriol and 25-hydroxycholesterol accumulate in ATP-binding cassette transporter G1 (ABCG1)-deficiency
چکیده انگلیسی


- 3β,5α,6β-cholestanetriol and 25-hydroxycholesterol accumulate in Abcg1−/− mice.
- These two oxysterols are major substrates for ABCG1-mediated export from cells.
- Cholesterol is poor substrate for ABCG1-mediated transport.
- Protecting against oxysterol-induced cytotoxicity is primary function of ABCG1.

ObjectiveOxysterols are oxidized derivatives of sterols that have cytotoxic effects and are potent regulators of diverse cellular functions. Efficient oxysterol removal by the sub-family G member 1 of the ATP-binding cassette transporters (ABCG1) is essential for cell survival and control of cellular processes. However, the specific role of ABCG1 in the transport of various oxysterol species has been not systematically investigated to date. Here, we examined the involvement of ABCG1 in the oxysterol metabolism by studying oxysterol tissue levels in a mouse model of Abcg1-deficiency.Methods and resultsAnalysis of lung tissue of Abcg1−/− mice on a standard diet revealed that 3β,5α,6β-cholestanetriol (CT) and 25-hydroxycholesterol (HC) accumulated at more than 100-fold higher levels in comparison to wild-type mice. 24S-HC and 27-HC levels were also elevated, but were minor constituents. A radiolabeled assay employing regulable ABCG1-expressing HeLa cell lines revealed that 25-HC export to albumin was dependent on functional ABCG1 expression and could be blocked by an excess of unlabeled 25-HC or 27-HC. In this cell line, 25-HC at low doses triggered mitochondrial membrane potential, and reactive oxygen species production, which are both indirect indicators of cellular energy expenditure.ConclusionOur results suggest that 25-HC and CT are physiologic substrates for ABCG1. Excessive accumulation of these oxysterols may explain the increased rate of cell death and the inflammatory phenotype observed in Abcg1-deficient animals and cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 235, Issue 1, July 2014, Pages 122-129
نویسندگان
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