Linked Life Data

8246131

Source:http://linkedlifedata.com/resource/pubmed/id/8246131

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1994-1-6
pubmed:abstractText
The basic abnormality in myasthenia gravis is the depletion of acetylcholine receptors (AChRs) at neuromuscular junctions, which is due in part to excessive endocytosis brought about by the action of pathogenic antibodies. We asked whether 3-deazaadenosine (3DZA), an inhibitor of phospholipid methylation, could decrease the rate of endocytosis of muscle AChRs and thereby interfere with this pathological process. The rationale for the use of 3DZA is that methylation of phospholipids alters membrane properties, and inhibition of methyltransferase reactions is known to slow the process of endocytosis. In this study, we have tested the effects of 3DZA and other methylation inhibitors on the degradation and synthesis of AChRs in an in vitro model of myasthenia gravis, using primary rat skeletal muscle cultures and serum from human myasthenic patients. In normal cultures (without myasthenic serum), 3DZA inhibited AChR degradation with a broad dose-response relationship, beginning as low as 2 microM (P < .0001). There was no acute effect on synthesis of AChRs or on other measures of muscle cell integrity. When human myasthenic serum was added to the cultures to accelerate the endocytosis and degradation of AChRs, 3DZA still potently inhibited the degradation rate. Because the drug allows accumulation of AChRs in the surface membrane of the muscle cell by reducing endocytotic degradation, it provides a potential strategy for therapy in human myasthenia gravis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-3565
pubmed:author
pubmed:issnType
Print
pubmed:volume
267
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
582-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
3-Deazaadenosine: a therapeutic strategy for myasthenia gravis by decreasing the endocytosis of acetylcholine receptors.
pubmed:affiliation
Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, Maryland 21287-7519.
pubmed:publicationType
Journal Article, Comparative Study, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't