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A short synthetic peptide that mimics apolipoprotein-A1 mobilizes globotriaosylceramide and cholesterol in Fabry disease fibroblasts.

Thursday, November 07, 2013 — Poster Session II

12:00 p.m. – 2:00 p.m.

FAES Academic Center (Upper-Level Terrace)




  • U.H. Schueler Hoffman
  • C.R. Kaneski
  • N. Dwyer
  • S. Demosky
  • J. Blanchette-Mackie
  • J. Hanover
  • R.O. Brady
  • A. Remaley


Fabry disease is an X-linked sphingolipid storage disorder caused by deficiency of the lysosomal enzyme α-galactosidase A, resulting in the intracellular accumulation of globotriaosylceramide (Gb3). We found that Gb3 storage also correlates with accumulation of endosomal -/ lysosomal- cholesterol in Fabry fibroblasts. This cholesterol accumulation may contribute to the phenotypic pathology of Fabry disease by slowing endosomal-lysosomal trafficking. We found that LDL receptor expression is not down-regulated in Fabry fibroblasts resulting in accumulation of both cholesterol and Gb3. Dr. Alan Remaley’s group (NHLBI) has produced a short synthetic peptide (5A-palmitoyl oleoyl- phosphatidyl choline = 5APOPC) that mimics apolipoprotein-A1, the main protein component of high density lipoprotein (HDL) that mediates the efflux of cholesterol from cells via the ATP-binding cassette transporter. In our studies, we used 5APOPC and HDL to remove cholesterol from Fabry fibroblasts to examine the fate of accumulated cellular Gb3. Using Immunostaining techniques; we could show that 5APOPC is highly effective for depleting cholesterol and Gb3 in these cells. 5APOPC restores the Apo A1-mediated cholesterol efflux which leads to mobilization of cholesterol and reduction of Gb3 in Fabry fibroblasts.

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