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Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction

Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction

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Prüfsumme: MD5:7c030d40041675ccef260796c1177f4e

WENZEL, Philip, Swenja SCHUHMACHER, Joachim KIENHÖFER, Johanna MÜLLER, Marcus HORTMANN, Matthias OELZE, Eberhard SCHULZ, Nicolai TREIBER, Toshihiro KAWAMOTO, Karin SCHARFFETTER-KOCHANEK, Thomas MÜNZEL, Alexander BÜRKLE, Markus Michael BACHSCHMID, Andreas DAIBER, 2008. Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction. In: Cardiovascular Research. 80(2), pp. 280-289. ISSN 0008-6363. eISSN 1755-3245

@article{Wenzel2008Manga-8544, title={Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction}, year={2008}, number={2}, volume={80}, issn={0008-6363}, journal={Cardiovascular Research}, pages={280--289}, author={Wenzel, Philip and Schuhmacher, Swenja and Kienhöfer, Joachim and Müller, Johanna and Hortmann, Marcus and Oelze, Matthias and Schulz, Eberhard and Treiber, Nicolai and Kawamoto, Toshihiro and Scharffetter-Kochanek, Karin and Münzel, Thomas and Bürkle, Alexander and Bachschmid, Markus Michael and Daiber, Andreas} }

Scharffetter-Kochanek, Karin Aims<br />Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a higher risk of thrombotic events. These effects can be explained by a reduction in free bioavailable nitric oxide that is inactivated by an age-dependent increase in superoxide formation. In the present study, mitochondria as a source of reactive oxygen species (ROS) and the contribution of manganese superoxide dismutase (MnSOD, SOD-2) and aldehyde dehydrogenase (ALDH-2) were investigated.<br /><br />Methods and results<br />Age-dependent effects on vascular function were determined in aortas of C57/Bl6 wild-type (WT), ALDH-22/2, MnSOD+/+, and MnSOD+/ mice by isometric tension measurements in organ chambers. Mitochondrial ROS formation was measured by luminol (L-012)-enhanced chemiluminescence and 2-hydroxyethidium formation with an HPLC-based assay in isolatedheart mitochondria. ROS-mediated mitochondrial DNA (mtDNA) damage was detected by a novel and modified version of the fluorescent-detection alkaline DNA unwinding (FADU) assay. Endothelial dysfunction was observed in aged C57/Bl6 WT mice in parallel to increased mitochondrial ROS formation and oxidative mtDNA damage. In contrast, middle-aged ALDH-22/2 mice showed a marked vascular dysfunction that was similar in old ALDH-22/2 mice suggesting that ALDH-2 exerts agedependent vasoprotective effects. Aged MnSOD+/2 mice showed the most pronounced phenotype such as severely impaired vasorelaxation, highest levels of mitochondrial ROS formation and mtDNA damage.<br /><br />Conclusion<br />The correlation between mtROS formation and acetylcholine-dependent relaxation revealed that mitochondrial radical formation significantly contributes to age-dependent endothelial dysfunction. Oelze, Matthias Kienhöfer, Joachim 2011-03-24T17:44:33Z 2008 deposit-license Bürkle, Alexander Kienhöfer, Joachim Schuhmacher, Swenja Treiber, Nicolai First publ. in: Cardiovascular Research 80 (2008), 2, pp. 280-289 Daiber, Andreas Daiber, Andreas Kawamoto, Toshihiro Schuhmacher, Swenja Müller, Johanna Wenzel, Philip Münzel, Thomas Schulz, Eberhard Scharffetter-Kochanek, Karin Kawamoto, Toshihiro Bachschmid, Markus Michael Wenzel, Philip Treiber, Nicolai 2011-03-24T17:44:33Z Oelze, Matthias Schulz, Eberhard Hortmann, Marcus Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction eng application/pdf Bürkle, Alexander Münzel, Thomas Hortmann, Marcus Müller, Johanna Bachschmid, Markus Michael

Dateiabrufe seit 01.10.2014 (Informationen über die Zugriffsstatistik)

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