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| Content Provider | PubMed Central |
|---|---|
| Author | Angela, Arciello Marco, Nadia De Giudice, Rita Del Guglielmi, Fulvio Pucci, Piero Annalisa, Relini Monti, Daria Maria Piccoli, Renata |
| Copyright Year | 2011 |
| Abstract | Apolipoprotein A-I (ApoA-I) is an extracellular lipid acceptor, whose role in cholesterol efflux and high-density lipoprotein formation is mediated by ATP-binding cassette transporter A1 (ABCA1). Nevertheless, some ApoA-I variants are associated to systemic forms of amyloidosis, characterized by extracellular fibril deposition in peripheral organs. Heart amyloid fibrils were found to be mainly constituted by the 93-residue N-terminal fragment of ApoA-I, named [1–93]ApoA-I. In this paper, rat cardiomyoblasts were used as target cells to analyse binding, internalization and intracellular fate of the fibrillogenic polypeptide in comparison to full-length ApoA-I. We provide evidence that the polypeptide: (i) binds to specific sites on cell membrane (Kd= 5.90 ± 0.70 × 10−7 M), where it partially co-localizes with ABCA1, as also described for ApoA-I; (ii) is internalized mostly by chlatrin-mediated endocytosis and lipid rafts, whereas ApoA-I is internalized preferentially by chlatrin-coated pits and macropinocytosis and (iii) is rapidly degraded by proteasome and lysosomes, whereas ApoA-I partially co-localizes with recycling endosomes. Vice versa, amyloid fibrils, obtained by in vitro aggregation of [1–93]ApoA-I, were found to be unable to enter the cells. We propose that internalization and intracellular degradation of [1–93]ApoA-I may divert the polypeptide from amyloid fibril formation and contribute to the slow progression and late onset that characterize this pathology. |
| Related Links | http://dx.doi.org/10.1111/j.1582-4934.2011.01271.x |
| Ending Page | 2663 |
| Page Count | 12 |
| Starting Page | 2652 |
| File Format | |
| ISSN | 15824934 |
| e-ISSN | 15824934 |
| Journal | Journal of Cellular and Molecular Medicine |
| Issue Number | 12 |
| Volume Number | 15 |
| Language | English |
| Publisher | Blackwell Publishing Ltd |
| Publisher Date | 2011-12-01 |
| Access Restriction | Open |
| Rights Holder | Blackwell Publishing Ltd |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Molecular Medicine |
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