Linked Life Data

20601097

Source:http://linkedlifedata.com/resource/pubmed/id/20601097

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-11-24
pubmed:abstractText
Inosine triphosphate pyrophosphatase (ITPA protein) (EC 3.6.1.19) hydrolyzes deaminated purine nucleoside triphosphates, such as ITP and dITP, to their corresponding purine nucleoside monophosphate and pyrophosphate. In mammals, this enzyme is encoded by the Itpa gene. Using the Itpa gene-disrupted mouse as a model, we have elucidated the biological significance of the ITPA protein and its substrates, ITP and dITP. Itpa(-/-) mice exhibited peri- or post-natal lethality dependent on the genetic background. The heart of the Itpa(-/-) mouse was found to be structurally and functionally abnormal. Significantly higher levels of deoxyinosine and inosine were detected in nuclear DNA and RNA prepared from Itpa(-/-) embryos compared to wild type embryos. In addition, an accumulation of ITP was observed in the erythrocytes of Itpa(-/-) mice. We found that Itpa(-/-) primary mouse embryonic fibroblasts (MEFs), which have no detectable ability to generate IMP from ITP in whole cell extracts, exhibited a prolonged population-doubling time, increased chromosome abnormalities and accumulation of single-strand breaks in their nuclear DNA, in comparison to primary MEFs prepared from wild type embryos. These results revealed that (1) ITP and dITP are spontaneously produced in vivo and (2) accumulation of ITP and dITP is responsible for the harmful effects observed in the Itpa(-/-) mouse. In addition to its effect as the precursor nucleotide for RNA transcription, ITP has the potential to influence the activity of ATP/GTP-binding proteins. The biological significance of ITP and dITP in the nucleotide pool remains to be elucidated.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0027-5107
pubmed:author
pubmed:copyrightInfo
2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
703
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
43-50
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
ITPA protein, an enzyme that eliminates deaminated purine nucleoside triphosphates in cells.
pubmed:affiliation
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. sakumi@bioreg.kyushu-u.ac.jp
pubmed:publicationType
Journal Article, Review, Research Support, Non-U.S. Gov't