Opposite effects of endotoxin on mitochondrial and endoplasmic reticulum functions.
In this study, we determined functional integrity and reactive oxygen species generation in mitochondria and endoplasmic reticulum in liver of rats subjected to endotoxic shock to clarify whether intracellular reactive oxygen species (ROS) destabilize cellular integrity causing necrosis in rats challenged with lipopolysaccharide (LPS). LPS caused drastically increased plasma levels of alanine aminotransferase, suggesting damage to plasma membranes of liver cells. Liver necrosis was confirmed by histological examination. LPS induced a significant increase in ROS production in rat liver mitochondria (RLM), but did not impair mitochondrial function. In contrast to mitochondria, enzymatic activity and ROS production of cytochrome P450 were lower in microsomal fraction obtained from LPS-treated animals, suggesting the dysfunction of endoplasmic reticulum. Protein patterns obtained from RLM by two-dimensional electrophoresis showed significant upregulation of mitochondrial superoxide dismutase by LPS. We hypothesize that upregulation of this enzyme protects mitochondria against mitochondrial ROS, but does not protect other cellular compartments such as endoplasmic reticulum and plasma membrane causing necrosis.
Kozlov
Andrey V
AV
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology in the AUVA research center, Donaueschingen Street 13, A-1200 Vienna, Austria. Andrey.Kozlov@lbitrauma.org
Gille
Lars
L
Miller
Ingrid
I
Piskernik
Christina
C
Haindl
Susanne
S
Staniek
Katrin
K
Nohl
Hans
H
Bahrami
Soheyl
S
Ohlinger
Wolfgang
W
Gemeiner
Manfred
M
Redl
Heinz
H
D000818:Animals; D015415:Biomarkers; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000502:physiology; D004731:Endotoxins / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase / Q000378:metabolism
D015415:Biomarkers; D004731:Endotoxins; D008070:Lipopolysaccharides; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase