Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis.
OBJECTIVE
The responses to bacterial lipopolysaccharide (LPS) damage mitochondria by generating oxidative stress within the organelles. We postulated that LPS damages heart mitochondrial DNA and protein by oxidation, and that this is recovered by oxidative mechanisms of mitochondrial biogenesis.


RESULTS
Systemic crude E. coli LPS administration decreased mtDNA copy number and mtDNA gene transcription in rat heart caused by oxidant deletion of mtDNA. The fall in copy number was reflected in proteomic expression of several mitochondria-encoded subunits of Complexes I, IV, and V. Recovery of mtDNA copy number involved biogenesis as indicated by mitochondrial transcription factor A (Tfam) and DNA polymerase-gamma expression. The transcriptional response also included nuclear accumulation of peroxisome proliferator-activated receptor-gamma co-activator 1 (PGC-1) and mRNA expression for redox-regulated nuclear respiratory factors (NRF-1 and -2).


CONCLUSIONS
These novel findings disclose a duality of reactive oxygen species (ROS) effect in the heart's response to LPS in which oxidative mitochondrial damage is opposed by oxidant stimulation of biogenesis.
Department of Medicine, Duke University Medical Center, 0590 CR II Building, Duke South Hospital Trent Drive, Durham, NC 27710, USA.
Hagir B
HB
Suliman
Karen E
KE
Welty-Wolf
Marthasue
M
Carraway
Lynn
L
Tatro
Claude A
CA
Piantadosi
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000032:analysis; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D049109:Cell Proliferation; D004272:DNA, Mitochondrial; D017353:Gene Deletion; D007473:Ion Channels; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D026901:Membrane Transport Proteins / Q000032:analysis; D008929:Mitochondria, Heart / Q000187:drug effects*; D024101:Mitochondrial Proteins / Q000032:analysis; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D018384:Oxidative Stress; D010101:Oxygen Consumption; D051381:Rats; D011919:Rats, Inbred Strains; D014157:Transcription Factors / Q000032:analysis; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3
D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D007473:Ion Channels; D008070:Lipopolysaccharides; D026901:Membrane Transport Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1; D009320:Atrial Natriuretic Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases