Linked Life Data

16230352

Source:http://linkedlifedata.com/resource/pubmed/id/16230352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-1-12
pubmed:abstractText
The nuclear expression of mitochondrial transcription factor A (Tfam), which is required for mitochondrial DNA (mtDNA) transcription and replication, must be linked to cellular energy needs. Because respiration generates reactive oxygen species as a side-product, we tested the idea that reactive oxygen species regulate Tfam expression through phosphorylation of nuclear respiratory factor (NRF-1) and binding to the Tfam promoter. In mitochondria-rich rat hepatoma cells that overexpress NRF-1, basal and oxidant-induced increases were found in Tfam expression and mtDNA content. Specific binding of NRF-1 to Tfam promoter was demonstrated by electrophoretic mobility shift assay and chromatin immunoprecipitation. NRF-1-Tfam binding was augmented under pro-oxidant conditions. NRF-1 gene silencing produced 1:1 knockdown of Tfam expression and decreased mtDNA content. To evaluate oxidation-reduction (redox) regulation of NRF-1 in Tfam expression, blockade of upstream phosphatidylinositol 3-kinase was used to demonstrate loss of oxidant stimulation of NRF-1 phosphorylation and Tfam expression. The oxidant response was also abrogated by specific inhibition of Akt/protein kinase B. Examination of the NRF-1 amino acid sequence revealed an Akt phosphorylation consensus at which site-directed mutagenesis abolished NRF-1 phosphorylation by Akt. Finally, Akt phosphorylation and NRF-1 translocation predictably lacked oxidant regulation in a cancer line having no PTEN tumor suppressor (HCC1937 cells). This study discloses novel redox regulation of NRF-1 phosphorylation and nuclear translocation by phosphatidylinositol 3,4,5-triphosphate kinase/Akt signaling in controlling Tfam induction by an anti-oxidant pro-survival network.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
6
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
324-33
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16230352-5' Flanking Region, pubmed-meshheading:16230352-Animals, pubmed-meshheading:16230352-Base Sequence, pubmed-meshheading:16230352-Carcinoma, Hepatocellular, pubmed-meshheading:16230352-Cell Line, Tumor, pubmed-meshheading:16230352-DNA, Mitochondrial, pubmed-meshheading:16230352-Gene Expression Regulation, pubmed-meshheading:16230352-Gene Silencing, pubmed-meshheading:16230352-Liver Neoplasms, pubmed-meshheading:16230352-Molecular Sequence Data, pubmed-meshheading:16230352-Nuclear Respiratory Factor 1, pubmed-meshheading:16230352-Oxidants, pubmed-meshheading:16230352-Oxidation-Reduction, pubmed-meshheading:16230352-Phosphorylation, pubmed-meshheading:16230352-Promoter Regions, Genetic, pubmed-meshheading:16230352-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16230352-Rats, pubmed-meshheading:16230352-Transcription, Genetic, pubmed-meshheading:16230352-Transcription Factors
pubmed:year
2006
pubmed:articleTitle
Mitochondrial transcription factor A induction by redox activation of nuclear respiratory factor 1.
pubmed:affiliation
Department of Medicine, Duke University, Medical Center, Durham, North Carolina 27710, USA. piant001@mc.duke.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural