Linked Life Data

11727924

Source:http://linkedlifedata.com/resource/pubmed/id/11727924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2001-11-30
pubmed:abstractText
The increase in intracellular pH (pHi) associated with various tumour cells triggers changes in gene expression. Similar adaptations also occur as part of the physiological response to changes in acid base balance. For example, during metabolic acidosis, increased renal ammoniagenesis and bicarbonate synthesis are sustained by the increased expression of various transport proteins and key enzymes of glutamine metabolism. In rat kidney, increased expression of the mitochondrial glutaminase (GA) and glutamate dehydrogenase (GDH) results from stabilization of their respective mRNAs. The 3'-untranslated region (UTR) of the GA mRNA contains a direct repeat of an 8-base AU sequence that functions as a pH-response element. This sequence exhibits a high affinity and specificity for z-crystallin. The same protein binds to two separate, but homologous, 8-base AU sequences within the 3'-UTR of the GDH mRNA. The apparent binding activity of z-crystallin is increased significantly during onset of metabolic acidosis. Thus, increased binding of z-crystallin may initiate the pH-responsive stabilization of the two mRNAs. In contrast, induction of the phosphoenolpyruvate carboxykinase (PEPCK) gene occurs at the transcriptional level. In LLC-PK1-FBPase+ kidney cells, a decrease in pHi leads to activation of the p38 stress-activated protein kinase and subsequent phosphorylation of ATF-2. This transcription factor binds to the CRE-1 element within the promoter of the PEPCK gene to enhance transcription. Similar mechanisms may contribute to altered gene expression in tumour cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1528-2511
pubmed:author
pubmed:issnType
Print
pubmed:volume
240
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
100-11; discussion 111-4
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
pH regulation of renal gene expression.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, Colorado State University, Fort Collins 80523-1870, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't