Linked Life Data

12692154

Source:http://linkedlifedata.com/resource/pubmed/id/12692154

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
Pt 11
pubmed:dateCreated
2003-5-5
pubmed:abstractText
The biosynthesis of heparan sulfate, present on the cell surface and in the basal lamina surrounding cells, is a multistep process in which each step is mediated by a specific enzyme. The initial modification of the precursor polysaccharide, N-deacetylation followed by N-sulfation of selected N-acetyl-D-glucosamine residues, is catalyzed by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST). This event is a key step that regulates the overall sulfate content of the polysaccharide. Here, we report on the effects of NDST deficiency on Ca2+ kinetics in myotubes from NDST-1- and NDST-2-deficient mice, indicating a novel role for heparan sulfate in skeletal muscle physiology. Immunostaining for specific heparan sulfate epitopes showed major changes in the heparan sulfate composition in skeletal muscle tissue derived from NDST-1-/- mice and NDST-/- cultured myotubes. Biochemical analysis indicates a relative decrease in both N-sulfation and 2-O-sulfation of skeletal muscle heparan sulfate. The core protein of heparan sulfate proteoglycan perlecan was not affected, as judged by immunohistochemistry. Also, acetylcholine receptor clustering and the occurrence of other ion channels involved in excitation-contraction coupling were not altered. In NDST-2-/- mice and heterozygous mice no changes in heparan sulfate composition were observed. Using high-speed UV confocal laser scanning microscopy, aberrant Ca2+ kinetics were observed in NDST-1-/- myotubes, but not in NDST-2-/- or heterozygous myotubes. Electrically induced Ca2+ spikes had significantly lower amplitudes, and a reduced removal rate of cytosolic Ca2+, indicating the importance of heparan sulfate in muscle Ca2+ kinetics.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9533
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2187-93
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Disturbed Ca2+ kinetics in N-deacetylase/N-sulfotransferase-1 defective myotubes.
pubmed:affiliation
Department of Biochemistry 194, University Medical Center, NCMLS, 6500 HB Nijmegen, The Netherlands.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't