L. Boltzmann Institute for Experimental and Clinical Traumatology
Donaueschingen Str. 13
1200 Vienna
Austria
andrey.kozlov@trauma.lbg.ac.at
http://trauma.lbg.ac.at
Research interests are focused on the understanding of molecular mechanisms causing organ failure in critical care diseases, in order to develop new diagnostic and therapeutic methods. Mechanisms leading to cellular dysfunction and cell death are the major part of our research. Our experimental models include systemic and local inflammatory response, ischemia-reperfusion injury, shock, neurotrauma, and comprise in vivo models, cell/tissue culture models, and experiments with isolated subcellular organelles.
(i) Mitochondrial function/dysfunction.
(ii) Endoplasmic reticulum function/dysfunction.
(iii) Oxidative stress and iron metabolism.
(iv) Pharmacology and toxicology of nitric oxide.
(v) Antioxidant defence systems.
(vi) Biomedical applications of low temperature electron paramagnetic resonance spectroscopy.
Abstract:
We seek to answer the following specific research questions.
What is the impact of mitochondrial dysfunction? This study focuses on changes of mitochondrial functions and patho-physiological impact of these changes in our experimental models. Particular attention is given to signalling pathways regulated by mitochondrial reactive oxygen and nitrogen species.
How to protect mitochondria? Positively charged hydrophobic molecules accumulate in mitochondria at 1000 fold greater concentrations compared to cytosol. This is due to very high membrane potential across the inner mitochondrial membrane. On the base of this phenomenon we try to recover mitochondrial dysfunction using specific mitochondria targeted drugs using positively charged molecules as a mitochondria targeted carrier.
What is the impact of endoplasmatic reticulum (ER) stress? Inflammatory response and ischemia-reperfusion have recently been shown to induce ER-stress and the unfolded protein response (UPR) aiming to recover ER. Our recent data show that under inflammatory conditions UPR neither recovers ER stress nor executes apoptosis creating a pool of living but non-functional cells. Currently we are trying to understand mechanisms and pathological relevance of this phenomenon.
What is the relevance of impaired crosstalk between subcellular organelles? This study is focused on the cross talk between mitochondria, nucleus, and endoplasmic reticulum. The impairment of this communication seems to be very important issue, particular upon inflammation.
What is the impact of nitric oxide synthase (NOS )independent nitric oxide (NO) production? It has been shown, that under ischemic conditions NO, a potent signalling molecule inducing vasodilatation, cytoprotection and other important pathways, is produced through an NOS-independent pathway. Our current aim is to clarify the pathophysiological relevance of this NOS-independent pathway and estimate its possible therapeutic potential, particular upon hypoxia and ischemia.
There are also few other research areas addressing the impact of activation of heme oxygenase (HO); pathophysiological impact of free iron; trapping of RONS in organs in vivo in order to develop diagnostic and therapeutic methods.
Techniques:
Electron spin resonance (Magnettech, Germany)
High resolution respirometer (Oroboros, Austria)
Confocal microscope (Zeiss, Germany)
Electrochemical determination of NO, H2O2 (WPI, USA)
Cytomics FC500 flow cytometer (Beckmann Coulter, Austria)
Sievers NOA-280i nitric oxide analyser (Analytix Ltd, UK)
Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?
Kozlov AV, Bahrami S, Calzia E, Dungel P, Gille L, Kuznetsov AV, Troppmair J.
Ann Intensive Care. 2011 Sep 26;1(1):41. Review.
Effect of estrogen on mitochondrial function and intracellular stress markers in rat liver and kidney following trauma-hemorrhagic shock and prolonged hypotension.
Kozlov AV, Duvigneau JC, Hyatt TC, Raju R, Behling T, Hartl RT, Staniek K, Miller I, Gregor W, Redl H, Chaudry IH.
Mol Med. 2010 Jul-Aug;16(7-8):254-61.
Nitrite as regulator of hypoxic signaling in mammalian physiology.
van Faassen EE, Bahrami S, Feelisch M, Hogg N, Kelm M, Kim-Shapiro DB, Kozlov AV, Li H, Lundberg JO, Mason R, Nohl H, Rassaf T, Samouilov A, Slama-Schwok A, Shiva S, Vanin AF, Weitzberg E, Zweier J, Gladwin MT
Med Res Rev. 2009 Sep;29(5):683-741. Review.
A novel endotoxin-induced pathway: upregulation of heme oxygenase 1, accumulation of free iron, and free iron-mediated mitochondrial dysfunction.
Duvigneau JC, Piskernik C, Haindl S, Kloesch B, Hartl RT, Hüttemann M, Lee I, Ebel T, Moldzio R, Gemeiner M, Redl H, Kozlov AV.
Lab Invest. 2008 Jan;88(1):70-7.
Illumination with blue light reactivates respiratory activity of mitochondria inhibited by nitric oxide, but not by glycerol trinitrate.
Dungel P, Mittermayr R, Haindl S, Osipov A, Wagner C, Redl H, Kozlov AV.
Arch Biochem Biophys. 2008 Mar 15;471(2):109-15. Epub 2008 Jan 19.