PMID: 14707133

 

    Legend: Gene, Sites

Title : Involvement of glycosylphosphatidylinositol-linked ceruloplasmin in the copper/zinc-nitric oxide-dependent degradation of glypican-1 heparan sulfate in rat C6 glioma cells

Abstract :

1. The core protein of glypican-1 , a glycosylphosphatidylinositol-linked heparan sulfate proteoglycan, can bind Cu(II) or Zn(II) ions and undergo S-nitrosylation in the presence of nitric oxide
2. Cu(II)-to-Cu(I)-reduction supports extensive and permanent nitrosothiol formation, whereas Zn(II) ions appear to support a more limited, possibly transient one
3. Ascorbate induces release of nitric oxide, which catalyzes deaminative degradation of the heparan sulfate chains on the same core protein
4. Although free Zn(II) ions support a more limited degradation, Cu(II) ions support a more extensive self-pruning process
5. Here, we have investigated processing of glypican-1 in rat C6 glioma cells and the possible participation of the copper-containing glycosylphosphatidylinositol-linked splice variant of ceruloplasmin variant of ceruloplasmin in nitrosothiol formation
6. Confocal microscopy demonstrated colocalization of glypican-1 and ceruloplasmin in endosomal compartments
7. Ascorbate induced extensive, Zn(II)-supported heparan sulfate degradation, which could be demonstrated using a specific zinc probe
8. RNA interference silencing of ceruloplasmin expression reduced the extent of Zn(II)-supported degradation
9. In cell-free experiments, the presence of free Zn(II) ions prevented free Cu(II) ion from binding to glypican-1 and precluded extensive heparan sulfate autodegradation
10. However, in the presence of Cu(II)-loaded ceruloplasmin , heparan sulfate in Zn(II)-loaded glypican-1 underwent extensive, ascorbate-induced degradation
11. We propose that the Cu(II)-to-Cu(I)-reduction that is required for S-nitrosylation of glypican-1 can take place on ceruloplasmin and thereby ensure extensive glypican-1 processing in the presence of free Zn(II) ions

Output (sent_index, trigger, protein, sugar, site):

• 1. glypican-1, , glypican-1, a glycosylphosphatidylinositol-linked heparan sulfate proteoglycan, -

Output(Part-Of) (sent_index, protein, site):

*Output_Site_Fusion* (sent_index, protein, sugar, site):

 

Protein	NCBI ID	SENTENCE INDEX
ceruloplasmin	24268	0,6,8,10,11
variant of ceruloplasmin	24268	5
glypican-1	58920	0,1,5,6,9,10,11