Copper-dependent autocleavage of glypican-1heparan sulfate by nitric oxide derived fromintrinsic nitrosothiols.
Ding, Kan LU ; Mani, Katrin LU
; Cheng, Fang
LU
; Belting, Mattias
LU
and Fransson, Lars-Åke
LU
(2002)
In Journal of Biological Chemistry
277(36).
p.33353-33360
- Abstract
- Cell-surface heparan sulfate proteoglycans facilitate uptake of growth-promoting polyamines [ [Belting, M., Borsig, L., Fuster, M.M., Brown, J.R., Persson, L., Fransson,L.-. and Esko, J.D. (2002) Proc. Natl. Acad. Sci. U.S.A., 99, 371-376] ]. Increased polyamine uptake correlates with an increased number of positively charged N-unsubstituted glucosamine units in the otherwise polyanionic heparan sulfate chains of glypican-1. During intracellular recycling of glypican-1 there is an NO-dependent deaminative cleavage of heparan sulfate at these glucosamine units, which would eliminate the positive charges [ [Ding, K., Sandgren, S., Mani, K., Belting, M. and Fransson, L.-. (2001) J. Biol. Chem., 276, 46779-46791] ]. Here, using both... (More)
- Cell-surface heparan sulfate proteoglycans facilitate uptake of growth-promoting polyamines [ [Belting, M., Borsig, L., Fuster, M.M., Brown, J.R., Persson, L., Fransson,L.-. and Esko, J.D. (2002) Proc. Natl. Acad. Sci. U.S.A., 99, 371-376] ]. Increased polyamine uptake correlates with an increased number of positively charged N-unsubstituted glucosamine units in the otherwise polyanionic heparan sulfate chains of glypican-1. During intracellular recycling of glypican-1 there is an NO-dependent deaminative cleavage of heparan sulfate at these glucosamine units, which would eliminate the positive charges [ [Ding, K., Sandgren, S., Mani, K., Belting, M. and Fransson, L.-. (2001) J. Biol. Chem., 276, 46779-46791] ]. Here, using both biochemical and microscopic techniques, we have identified and isolated S-nitrosylated forms of glypican-1 as well as low-charged glypican-1 glycoforms containing heparan sulfate chains rich in N-unsubstituted glucosamines. The latter were converted to high-charged species upon treatment of cells with 1 mM L-ascorbate, which releases NO from nitrosothiols, resulting in deaminative cleavage of heparan sulfate at the N-unsubstituted glucosamines. S-nitrosylation and subsequent deaminative cleavage were abrogated by inhibition of a Cu 2+ /Cu + -redox cycle. Under cell-free conditions, purified, S-nitrosylated glypican-1 was able to autocleave its heparan sulfate chains when NO-release was triggered by L-ascorbate. The heparan sulfate fragments generated in cells during this auto-catalytic process contained terminal anhydromannose residues. We conclude that the core protein of glypican-1 can slowly accumulate NO as nitrosothiols while Cu 2+ is reduced to Cu +. Subsequent release of NO results in efficient deaminative cleavage of the heparan sulfate chains attached to the same core protein while Cu + is oxidized to Cu 2+. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/109038
- author
- Ding, Kan
LU
; Mani, Katrin
LU
; Cheng, Fang
LU
; Belting, Mattias
LU
and Fransson, Lars-Åke
LU
- organization
- publishing date
- 2002
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Biological Chemistry
- volume
- 277
- issue
- 36
- pages
- 33353 - 33360
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- wos:000177859000124
- scopus:0037031909
- ISSN
- 1083-351X
- DOI
- 10.1074/jbc.M203383200
- language
- English
- LU publication?
- yes
- id
- 03a98506-d2c7-40cd-a203-ba841b823f11 (old id 109038)
- alternative location
- http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12084716&dopt=Abstract
- date added to LUP
- 2016-04-01 11:52:03
- date last changed
- 2023-09-01 10:17:54
@article{03a98506-d2c7-40cd-a203-ba841b823f11,
abstract = {{Cell-surface heparan sulfate proteoglycans facilitate uptake of growth-promoting polyamines [ [Belting, M., Borsig, L., Fuster, M.M., Brown, J.R., Persson, L., Fransson,L.-. and Esko, J.D. (2002) Proc. Natl. Acad. Sci. U.S.A., 99, 371-376] ]. Increased polyamine uptake correlates with an increased number of positively charged N-unsubstituted glucosamine units in the otherwise polyanionic heparan sulfate chains of glypican-1. During intracellular recycling of glypican-1 there is an NO-dependent deaminative cleavage of heparan sulfate at these glucosamine units, which would eliminate the positive charges [ [Ding, K., Sandgren, S., Mani, K., Belting, M. and Fransson, L.-. (2001) J. Biol. Chem., 276, 46779-46791] ]. Here, using both biochemical and microscopic techniques, we have identified and isolated S-nitrosylated forms of glypican-1 as well as low-charged glypican-1 glycoforms containing heparan sulfate chains rich in N-unsubstituted glucosamines. The latter were converted to high-charged species upon treatment of cells with 1 mM L-ascorbate, which releases NO from nitrosothiols, resulting in deaminative cleavage of heparan sulfate at the N-unsubstituted glucosamines. S-nitrosylation and subsequent deaminative cleavage were abrogated by inhibition of a Cu 2+ /Cu + -redox cycle. Under cell-free conditions, purified, S-nitrosylated glypican-1 was able to autocleave its heparan sulfate chains when NO-release was triggered by L-ascorbate. The heparan sulfate fragments generated in cells during this auto-catalytic process contained terminal anhydromannose residues. We conclude that the core protein of glypican-1 can slowly accumulate NO as nitrosothiols while Cu 2+ is reduced to Cu +. Subsequent release of NO results in efficient deaminative cleavage of the heparan sulfate chains attached to the same core protein while Cu + is oxidized to Cu 2+.}},
author = {{Ding, Kan and Mani, Katrin and Cheng, Fang and Belting, Mattias and Fransson, Lars-Åke}},
issn = {{1083-351X}},
language = {{eng}},
number = {{36}},
pages = {{33353--33360}},
publisher = {{American Society for Biochemistry and Molecular Biology}},
series = {{Journal of Biological Chemistry}},
title = {{Copper-dependent autocleavage of glypican-1heparan sulfate by nitric oxide derived fromintrinsic nitrosothiols.}},
url = {{http://dx.doi.org/10.1074/jbc.M203383200}},
doi = {{10.1074/jbc.M203383200}},
volume = {{277}},
year = {{2002}},
}