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

Wenzel, Philip; Schuhmacher, Swenja; Kienhöfer, Joachim; Müller, Johanna; Hortmann, Marcus; Oelze, Matthias; Schulz, Eberhard; Treiber, Nicolai; Kawamoto, Toshihiro; Scharffetter-Kochanek, Karin; Münzel, Thomas; Bürkle, Alexander; Bachschmid, Markus Michael; Daiber, Andreas

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

Dateien

2008_CardiovascRes_epub_Wenzel.pdfGröße: 439.18 KBDownloads: 381

Datum

2008

Autor:innen

Wenzel, Philip

Schuhmacher, Swenja

Kienhöfer, Joachim

Müller, Johanna

Hortmann, Marcus

Oelze, Matthias

Schulz, Eberhard

Treiber, Nicolai

Kawamoto, Toshihiro

Scharffetter-Kochanek, Karin

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Open Access-Veröffentlichung

Open Access Green

Sammlungen

Biologie

Publikationstyp

Zeitschriftenartikel

Publikationsstatus

Published

Erschienen in

Cardiovascular Research. 2008, 80(2), pp. 280-289. ISSN 0008-6363. eISSN 1755-3245. Available under: doi: 10.1093/cvr/cvn182

Zusammenfassung

Aims
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.

Methods and results
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.

Conclusion
The correlation between mtROS formation and acetylcholine-dependent relaxation revealed that mitochondrial radical formation significantly contributes to age-dependent endothelial dysfunction.

Fachgebiet (DDC)

570 Biowissenschaften, Biologie

Schlagwörter

Vascular dysfunction, Mitochondrial oxidative stress, Manganese superoxide dismutase, Mitochondrial aldehyde dehydrogenase, 8-oxodG

Zitieren

ISO 690

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. 2008, 80(2), pp. 280-289. ISSN 0008-6363. eISSN 1755-3245. Available under: doi: 10.1093/cvr/cvn182

BibTex

@article{Wenzel2008Manga-8544,
  year={2008},
  doi={10.1093/cvr/cvn182},
  title={Manganese superoxide dismutase and aldehyde dehydrogenase deficiency increase mitochondrial oxidative stress and aggravate age-dependent vascular dysfunction},
  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}
}

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Universitätsbibliographie

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