MiPsummer Programme pdf - Mitochondrial Physiology Society

68
Abstract # 37
Interplay between Mitochondrial Reactive Oxygene Species and Gene Expression
A. Weidinger, 1 S.Chaudary, 1 J.C. Duvigneau, 2 A. Müllebner, 2 H. Redl, 1 A.V. Kozlov 1
1
Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Donaueschingenstraße
13, 1200 Vienna
2
University of Veterinary Medicine Vienna, Institute for Medical Chemistry, Veterinärplatz 1, 1210
Vienna
Background and aim
Excessive systemic inflammatory response (SIR) causes multiple organ dysfunction and often
death. SIR induces elevated mitochondrial reactive oxygen species (mtROS) production. mtROS
have been shown to play an important role in intracellular signal-transduction. These reactive
species can be selectively trapped by mitochondria-targeted antioxidants (mtAOX). The aim of the
study was to compare biological effects of Mito-Tempo, a water-soluble mtAOX, and SkQ1*, a
fat-soluble mtAOX on inflammation.
Methods Inflammation in Sprague-Dawley rats was induced by lipopolysaccharide (8 mg/kg).
After 8 hrs, mtROS, lipid peroxidation products (TBA-RS), mitochondrial function and gene
expression were determined by electron paramagnetic resonance, calorimetry, high resolution
respirometry and RT-PCR, respectively.
Results Preliminary experiments revealed optimal concentrations of mtAOX which do not impair
mitochondrial function. These concentrations were 5 nmol/kg for SkQ1 and 50 nmol/kg for
Mito-Tempo. Inflammatory response resulted in increased mtROS generation and in elevated
TBA-RS levels. mtROS generation was inhibited only by Mito-Tempo but not by SkQ1, while both
substances led to a decrease of TBA-RS levels. Both, SkQ1 and Mito-Tempo regulated expression
of MnSOD, GRP78 and other enzymes related to SIR.
Conclusion Our data suggests that mtAOX may attenuate gene expression particularly those
relevant to SIR.
* SkQ1 was generously donated by V.P. Skulachev.