Linked Life Data

14990347

Source:http://linkedlifedata.com/resource/pubmed/id/14990347

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-3-1
pubmed:abstractText
Hereditary sensory neuropathy type I (HSN1) is a common degenerative disorder of peripheral sensory neurons. HSN1 is caused by mutations in the gene, encoding the long chain base 1 of serine palmitoyltransferase (SPT) [Nat. Genet. 27 (2001) 309]. Here, we show a 44% reduction of SPT activity in transformed lymphocytes from HSN1 patients with mutation T399G in the SPTLC1 gene. However, the decrease in SPT activity had no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death (apoptosis and necrosis). The removal of extracellular sphingolipids did not affect viability of HSN1 cells. We also found no significant difference in whole blood counts, viability, and permeability to Triton X-100 of primary lymphocytes from HSN1 patients. These results suggest that, despite the inhibition of mutant allele, the activity of nonmutant allele of STP may be sufficient for adequate sphingolipid biosynthesis and cell viability. Therefore, the neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effect(s) of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal protein(s) as in other neurodegenerations.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0006-3002
pubmed:author
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
1688
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
168-75
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells.
pubmed:affiliation
Neurobiology Laboratory, ANZAC Research Institute, Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2139, Australia. vdedov@med.usyd.edu.au
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't