|
 |
|
|
| The EMBO Journal
(2001) 20, 377–386, doi: 10.1093/emboj/20.3.377 |
|
| Sulfated glycans and elevated temperature stimulate PrPSc-dependent cell-free formation of protease-resistant prion protein |
|
|
| Cai'ne Wong1, Liang-Wen Xiong1, Motohiro Horiuchi2, Lynne Raymond1, Kathy Wehrly1, Bruce Chesebro1 and Byron Caughey1 |
|
|
1 Laboratory of Persistent Viral Diseases, Rocky Mountain Laboratories/NIH, 903 South 4th Street, Hamilton, MT 59840, USA 2 Department of Veterinary Public Health and Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido 080-8555, Japan To whom correspondence should be addressed Byron Caughey, byron_caughey@nih.gov Received 13 September 2000; Revised 30 November 2000; Accepted 30 November 2000. |
|
|
|
| Abstract |
|
| A conformational conversion of the normal, protease- sensitive prion protein (PrP-sen or PrPC) to a protease-resistant form (PrP-res or PrPSc) is commonly thought to be required in transmissible spongiform encephalopathies (TSEs). Endogenous sulfated glycosaminoglycans are associated with PrP-res deposits in vivo, suggesting that they may facilitate PrP-res formation. On the other hand, certain exogenous sulfated glycans can profoundly inhibit PrP-res accumulation and serve as prophylactic anti-TSE compounds in vivo. To investigate the seemingly paradoxical effects of sulfated glycans on PrP-res formation, we have assayed their direct effects on PrP conversion under physiologically compatible cell-free conditions. Heparan sulfate and pentosan polysulfate stimulated PrP-res formation. Conversion was stimulated further by increased temperature. Both elevated temperature and pentosan polysulfate promoted interspecies PrP conversion. Circular dichroism spectropolarimetry measurements showed that pentosan polysulfate induced a conformational change in PrP-sen that may potentiate its PrP-res-induced conversion. These results show that certain sulfated glycosaminoglycans can directly affect the PrP conversion reaction. Therefore, depending upon the circumstances, sulfated glycans may be either cofactors or inhibitors of this apparently pathogenic process. |
|
| Keywords: heparan sulfate, pentosan polysulfate, prion, scrapie, transmissible spongiform encephalopathy |
|
| |
| |
| |
 | Email link to a friend |
| |
 | Download PDF |
| |
 | Full text |
| |
| |
| |
 | Next article |
| |
 | Previous article |
| |
 | Table of contents |
| |
| |
| |
| |
 Register for table of contents by email | |
| |
| |
| |
