Hypoxia induces NO-dependent release of heparan sulfate in fibroblasts from the Alzheimer mouse Tg2576 by activation of nitrite reduction.
Cheng, Fang LU ; Bourseau-Guilmain, Erika LU ; Belting, Mattias LU ; Fransson, Lars-Åke LU and Mani, Katrin LU
(2016)
In Glycobiology
26(6).
p.623-634
- Abstract
- There is a functional relationship between the heparan sulfate proteoglycan glypican-1 and the amyloid precursor protein of Alzheimer disease. In wild-type mouse embryonic fibroblasts, expression and processing of the amyloid precursor protein is required for endosome-to-nucleus translocation of anhydromannose-containing heparan sulfate released from S-nitrosylated glypican-1 by ascorbate-induced, nitrosothiol-catalyzed deaminative cleavage. In fibroblasts from the transgenic Alzheimer mouse Tg2576 there is increased processing of the amyloid precursor protein to amyloid-β peptides. Simultaneously, there is spontaneous formation of anhydromannose-containing heparan sulfate by an unknown mechanism. We have explored the effect of hypoxia on... (More)
- There is a functional relationship between the heparan sulfate proteoglycan glypican-1 and the amyloid precursor protein of Alzheimer disease. In wild-type mouse embryonic fibroblasts, expression and processing of the amyloid precursor protein is required for endosome-to-nucleus translocation of anhydromannose-containing heparan sulfate released from S-nitrosylated glypican-1 by ascorbate-induced, nitrosothiol-catalyzed deaminative cleavage. In fibroblasts from the transgenic Alzheimer mouse Tg2576 there is increased processing of the amyloid precursor protein to amyloid-β peptides. Simultaneously, there is spontaneous formation of anhydromannose-containing heparan sulfate by an unknown mechanism. We have explored the effect of hypoxia on anhydromannose-containing heparan sulfate formation in wild-type and Tg2576 fibroblasts by deconvolution immunofluorescence microscopy and flow cytometry using an anhydromannose-specific monoclonal antibody and by (35)SO4-labeling experiments. Hypoxia prevented ascorbate-induced heparan sulfate release in wild-type fibroblasts, but induced an increased formation of anhydromannose-positive and (35)S-labeled heparan sulfate in Tg2576 fibroblasts. This appeared to be independent of glypican-1 S-nitrosylation as demonstrated by using a monoclonal antibody specific for S-nitrosylated glypican-1. In hypoxic wild-type fibroblasts, addition of nitrite to the medium restored anhydromannose-containing heparan sulfate formation. The increased release of anhydromannose-containing heparan sulfate in hypoxic Tg2576 fibroblasts did not require addition of nitrite. However, it was suppressed by inhibition of the nitrite reductase activity of xanthine oxidoreductase/aldehyde oxidase or by inhibition of p38 mitogen-activated protein kinase or by chelation of iron. We propose that normoxic Tg2576 fibroblasts maintain a high level of anhydromannose-containing heparan sulfate production by a stress-activated generation of nitric oxide from endogenous nitrite. This activation is enhanced by hypoxia. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8576734
- author
- Cheng, Fang
LU
; Bourseau-Guilmain, Erika
LU
; Belting, Mattias
LU
; Fransson, Lars-Åke
LU
and Mani, Katrin
LU
- organization
- publishing date
- 2016-01-20
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Glycobiology
- volume
- 26
- issue
- 6
- pages
- 12 pages
- publisher
- Oxford University Press
- external identifiers
-
- pmid:26791445
- scopus:84973354183
- pmid:26791445
- wos:000377611000010
- ISSN
- 1460-2423
- DOI
- 10.1093/glycob/cww007
- language
- English
- LU publication?
- yes
- id
- 41509de7-e727-4820-9f84-3c2f41bd0f90 (old id 8576734)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26791445?dopt=Abstract
- date added to LUP
- 2016-04-04 09:44:27
- date last changed
- 2023-10-18 06:56:43
@article{41509de7-e727-4820-9f84-3c2f41bd0f90,
abstract = {{There is a functional relationship between the heparan sulfate proteoglycan glypican-1 and the amyloid precursor protein of Alzheimer disease. In wild-type mouse embryonic fibroblasts, expression and processing of the amyloid precursor protein is required for endosome-to-nucleus translocation of anhydromannose-containing heparan sulfate released from S-nitrosylated glypican-1 by ascorbate-induced, nitrosothiol-catalyzed deaminative cleavage. In fibroblasts from the transgenic Alzheimer mouse Tg2576 there is increased processing of the amyloid precursor protein to amyloid-β peptides. Simultaneously, there is spontaneous formation of anhydromannose-containing heparan sulfate by an unknown mechanism. We have explored the effect of hypoxia on anhydromannose-containing heparan sulfate formation in wild-type and Tg2576 fibroblasts by deconvolution immunofluorescence microscopy and flow cytometry using an anhydromannose-specific monoclonal antibody and by (35)SO4-labeling experiments. Hypoxia prevented ascorbate-induced heparan sulfate release in wild-type fibroblasts, but induced an increased formation of anhydromannose-positive and (35)S-labeled heparan sulfate in Tg2576 fibroblasts. This appeared to be independent of glypican-1 S-nitrosylation as demonstrated by using a monoclonal antibody specific for S-nitrosylated glypican-1. In hypoxic wild-type fibroblasts, addition of nitrite to the medium restored anhydromannose-containing heparan sulfate formation. The increased release of anhydromannose-containing heparan sulfate in hypoxic Tg2576 fibroblasts did not require addition of nitrite. However, it was suppressed by inhibition of the nitrite reductase activity of xanthine oxidoreductase/aldehyde oxidase or by inhibition of p38 mitogen-activated protein kinase or by chelation of iron. We propose that normoxic Tg2576 fibroblasts maintain a high level of anhydromannose-containing heparan sulfate production by a stress-activated generation of nitric oxide from endogenous nitrite. This activation is enhanced by hypoxia.}},
author = {{Cheng, Fang and Bourseau-Guilmain, Erika and Belting, Mattias and Fransson, Lars-Åke and Mani, Katrin}},
issn = {{1460-2423}},
language = {{eng}},
month = {{01}},
number = {{6}},
pages = {{623--634}},
publisher = {{Oxford University Press}},
series = {{Glycobiology}},
title = {{Hypoxia induces NO-dependent release of heparan sulfate in fibroblasts from the Alzheimer mouse Tg2576 by activation of nitrite reduction.}},
url = {{https://lup.lub.lu.se/search/files/10992884/5404994.pdf}},
doi = {{10.1093/glycob/cww007}},
volume = {{26}},
year = {{2016}},
}