Linked Life Data

3114634

Source:http://linkedlifedata.com/resource/pubmed/id/3114634

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1987-10-20
pubmed:abstractText
The effect of D,L-alpha-difluoromethylornithine (DFMO) on thiol and polyamine levels in Trypanosoma brucei was investigated by isolating trypanosomes from infected rats treated with DFMO for 12-48 h. Concentrations of thiols, polyamines and other amino-compounds were measured by an automated high-performance liquid chromatography method. The levels of DFMO in rat plasma (0.02-1.34 mM) is similar to that found in the parasites (0.27-0.99 mM), concentrations which exceed the Ki of DFMO for T. brucei ornithine decarboxylase. Treatment with DFMO increases intracellular levels of ornithine, S-adenosylmethionine and decarboxylated S-adenosylmethionine and decreases putrescine and spermidine. Putrescine is undetectable after 12 h treatment with DFMO and after 48 h spermidine is decreased by 76%. By 48 h, the spermidine-glutathione conjugates glutathionylspermidine and dihydrotrypanothione (bis(glutathionyl)spermidine) are also decreased by 41 and 66%, respectively. In contrast, levels of glutathione show a slight increase. These changes in metabolite levels are consistent with the biosynthetic pathway proposed for Crithidia fasciculata, where trypanothione is synthesized from spermidine and glutathione via the intermediates N1- and N8-glutathionyl-spermidine. Trypanothione is thought to have two important roles in trypanosomatid metabolism: the maintenance of intracellular thiols in the correct redox state and in the removal of hydrogen peroxide and other hydroperoxides. Thus, it is proposed that depletion of this metabolite may be an important contributory factor to the selective toxic effect of DFMO, particularly in its synergistic effect with other trypanocidal drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0166-6851
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
185-91
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1987
pubmed:articleTitle
In vivo effects of difluoromethylornithine on trypanothione and polyamine levels in bloodstream forms of Trypanosoma brucei.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't