Search: onr:"swepub:oai:lup.lub.lu.se:41509de7-e727-4820-9f84-3c2f41bd0f90" >
Hypoxia induces NO-...
Hypoxia induces NO-dependent release of heparan sulfate in fibroblasts from the Alzheimer mouse Tg2576 by activation of nitrite reduction.
-
- Cheng, Fang (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
-
- Bourseau-Guilmain, Erika (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
-
- Belting, Mattias (author)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
-
show more...
-
- Fransson, Lars-Åke (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
-
- Mani, Katrin (author)
- Lund University,Lunds universitet,Glykobiologigruppen,Forskargrupper vid Lunds universitet,Glycobiology,Lund University Research Groups
-
show less...
-
(creator_code:org_t)
- 2016-01-20
- 2016
- English 12 s.
-
In: Glycobiology. - : Oxford University Press (OUP). - 1460-2423 .- 0959-6658. ; 26:6, s. 623-634
- Related links:
-
https://portal.resea... (primary) (free)
-
show more...
-
http://www.ncbi.nlm....
-
http://dx.doi.org/10...
-
https://academic.oup...
-
https://lup.lub.lu.s...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
Find in a library
To the university's database