RRC ID 43252
Author Kitamura H, Ito M, Yuasa T, Kikuguchi C, Hijikata A, Takayama M, Kimura Y, Yokoyama R, Kaji T, Ohara O.
Title Genome-wide identification and characterization of transcripts translationally regulated by bacterial lipopolysaccharide in macrophage-like J774.1 cells.
Journal Physiol Genomics
Abstract Although Escherichia coli LPS is known to elicit various proinflammatory responses in macrophages, its effect on the translational states of transcripts has not yet been explored on a genome-wide scale. To address this, we investigated the mRNA profiles in polysomal and free messenger ribonucleoprotein particle (mRNP) fractions of mouse macrophage-like J774.1 cells, using Affymetrix Mouse Genome 430 2.0 GeneChips. Comparison of the mRNA profiles in total cellular, polysomal, and free mRNP fractions enabled us to identify transcripts that were modulated at the translational level by LPS: among 19,791 transcripts, 115 and 418 were up- and downregulated at 1, 2, or 4 h after LPS stimulation (100 ng/ml) in a translation-dependent manner. Interestingly, gene ontology-based analysis suggested that translation-dependent downregulated genes frequently include those encoding proteins in the mitochondrial respiratory chain. In fact, the mRNA levels of some transcripts for complexes I, IV, and V in the mitochondrial respiratory chain were translationally downregulated, eventually contributing to the decline of their protein levels. Moreover, the amount of metabolically labeled cytochrome oxidase subunit Va in complex IV was decreased without any change of its mRNA level in total cellular fraction after LPS stimulation. Consistently, the total amounts and activities of complexes I and IV were attenuated by LPS stimulation, and the attenuation was independent of nitric oxide. These results demonstrated that translational suppression may play a critical role in the LPS-mediated attenuation of mitochondrial oxidative phosphorylation in a nitric oxide-independent manner in J774.1 cells.
Volume 33(1)
Pages 121-32
Published 2008-3-14
DOI 10.1152/physiolgenomics.00095.2007
PII 00095.2007
PMID 18230670
MeSH Animals Cell Line Electron Transport / drug effects Electron Transport / genetics Escherichia coli / chemistry Gene Expression Profiling Gene Expression Regulation / drug effects Genome* Lipopolysaccharides / pharmacology* Macrophages / drug effects* Macrophages / metabolism Mice Models, Biological NG-Nitroarginine Methyl Ester / pharmacology Oligonucleotide Array Sequence Analysis Protein Biosynthesis / drug effects* RNA, Messenger / classification RNA, Messenger / drug effects RNA, Messenger / metabolism*
IF 2.749
Times Cited 22
Human and Animal Cells J774.1(RCB0434)