Lipopolysaccharide induces oxidative cardiac mitochondrial damage and biogenesis
Hagir B Suliman1, Karen E Welty-Wolf, Marthasue Carraway
1Department of Medicine, Duke University Medical Center, 0590 CR II Building, Duke South Hospital Trent Drive, Durham, NC 27710, USA.
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.
Methods And 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.
Insights
Bacterial lipopolysaccharide (LPS) damages heart mitochondria through oxidative stress. However, the heart initiates mitochondrial biogenesis, using oxidative mechanisms to recover mitochondrial DNA and protein damage.
Area of Science:
- Cardiovascular Research
- Mitochondrial Biology
- Toxicology
Background:
- Bacterial lipopolysaccharide (LPS) induces oxidative stress, damaging cellular components.
- Mitochondria are particularly vulnerable to oxidative damage, impacting cellular energy production.
Purpose of the Study:
- To investigate the impact of LPS on heart mitochondrial DNA (mtDNA) and protein.
- To determine if oxidative mechanisms of mitochondrial biogenesis contribute to recovery from LPS-induced damage.
Main Methods:
- Rats were administered crude Escherichia coli LPS.
- Mitochondrial DNA copy number, gene transcription, and proteomic expression were analyzed.
- Expression of key biogenesis factors, including Tfam, PGC-1, and NRFs, was assessed.
Main Results:
- LPS administration decreased mtDNA copy number and transcription in rat hearts.
- Proteomic analysis revealed reduced expression of mitochondrial respiratory chain subunits.
- Recovery involved increased expression of Tfam, PGC-1, and NRFs, indicating biogenesis activation.
Conclusions:
- LPS induces oxidative damage to heart mitochondria, evidenced by decreased mtDNA.
- Oxidative stress paradoxically stimulates mitochondrial biogenesis for recovery.
- Reactive oxygen species (ROS) play a dual role in the heart's response to LPS.
Related Concept Videos
01:24Peroxisomes
01:16Necrosis
Morphological Manifestations of Necrosis
Necrotic cells show different types of morphological appearance depending on the type of tissue and infection. In coagulative necrosis, cells become anucleated and die, but their...
01:24Overview of Lipid Metabolism
Lipolysis: The Breakdown of Lipids:
Lipolysis is the process of breaking down lipids, particularly triglycerides, into glycerol and fatty acids. This process typically occurs in the adipose tissue and is triggered by various hormones, including glucagon and...
01:21Myocarditis I: Introduction