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Molecular mechanisms of the crosstalk between mitochondrial and NADPH oxidase derived reactive oxygen species in white blood cells – implications for cardiovascular diseases
Author(s) -
Steven Sebastian,
Schuhmacher Swenja,
Wenzel Philip,
Oelze Matthias,
Daub Steffen,
Scholz Alexander,
Xia Ning,
Schulz Eberhard,
Li Huige,
Lackner Karl J.,
Münzel Thomas,
Daiber Andreas
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.575.3
Subject(s) - nadph oxidase , apocynin , mitochondrial ros , reactive oxygen species , oxidative stress , knockout mouse , chemistry , crosstalk , microbiology and biotechnology , biology , pharmacology , biochemistry , receptor , physics , optics
Background Oxidants and antioxidant enzymes are involved in the development of many disease such as atherosclerosis. There are reports on a crosstalk between different sources of oxidative stress. With the present study we sought to determine the underlying mechanism of this crosstalk. Methods and results Complex III inhibitors were used to induce the Nox‐dependent oxidative burst by mitochondrial ROS (mtROS) in human neutrophils. Nox2 derived ROS were measured by a chemiluminescence assay. Inhibitors for the involved signaling cascade such as cyclosporine A (effects mitochondrial permeability transition pore [mPTP]), chelerythine (effects protein kinase C) and apocynin (effects Nox) were used. This crosstalk between mtROS and Nox was absent in white blood cells from p47 phox deficient mice (Nox2 subunit) or from cyclophilin D knockout mice (mPTP subunit), whereas this crosstalk was amplified in white blood cells from MnSOD +/− mice. We observed that increases in blood pressure, endothelial dysfunction or Nox activity were more pronounced in MnSOD +/− mice as compared to wild type‐mice. Conclusions Dikalov et al. have demonstrated that Nox derived ROS increases mtROS contributing to overall angiotensin‐II dependent cellular dysfunction. Our data show that mtROS trigger the activation of Nox, which may have severe effects on progression of cardiovascular diseases since it represents a feedback loop.