The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Role of Redox Signaling in the Autonomous Proliferative Response of Endothelial Cells to Hypoxia
Abstract
Endothelial cells exhibit an autonomous proliferative response to hypoxia, independent of paracrine effectors. In cultured endothelial cells of porcine aorta, we analyzed the signaling of this response, with a focus on the roles of redox signaling and the MEK/ERK pathway. Transient hypoxia (1 hour) stimulated proliferation by 61±4% (n=16; P <0.05 versus control), quantified after 24 hours normoxic postincubation. Hypoxia induced an activation of ERK2 and of NAD(P)H oxidase and a burst of reactive oxygen species (ROS), determined by DCF fluorescence. To inhibit the MEK/ERK pathway, we used PD 98059 (PD, 20 μmol/L); to downregulate NAD(P)H oxidase, we applied p22 phox antisense oligonucleotides; and to inhibit mitochondrial ROS generation, we used the ubiquinone derivate mitoQ (MQ, 10 μmol/L). All three inhibitions suppressed the proliferative response: PD inhibited NAD(P)H oxidase activation; p22 phox antisense transfection did not inhibit ERK2 activation, but suppressed ROS production; and MQ inhibited ERK2 activation and ROS production. The autonomous proliferative response depends on the MEK/ERK pathway and redox signaling steps upstream and downstream of ERK. Located upstream is ROS generation by mitochondria, downstream is NAD(P)H oxidase.
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“Also, dose/response studies demonstrated effects of mitoquinone extending an order of magnitude or more downward from the 1 μM (or higher) dose used in other reported studies of the cellular actions of this compound (25, 81, 283), some of which reported a mitoQ-induced resistance to apoptosis (25, 81).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [283]
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Metadata
- Authors
- Schäfer, M., Schäfer, C., Ewald, N., Piper, H. M., & Noll, T.
- Affiliations
- Justus-Liebig-Universität Gießen (DE)
- From the Physiologisches Institut, Justus-Liebig-Universität, Giessen, Germany.
- Venue
- Circulation Research
- Published
- 2003-05-16
- Volume
- 92
- Issue
- 9
- Pages
- 1010-1015
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2142734267
- Cited by
- 127
- References
- 23
- Citations by year
- 2024: 5 · 2022: 2 · 2020: 4 · 2019: 2 · 2017: 6 · 2016: 7 · 2015: 2 · 2014: 8 · 2013: 5 · 2012: 5
- FWCI
- 4.27
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Keywords
- endothelial cell proliferation, hypoxia, redox signaling, MEK/ERK signaling, ERK2 activation, NADPH oxidase, reactive oxygen species, mitochondrial reactive oxygen species, p22phox, MitoQ, PD98059, porcine aorta
- MeSH terms
- Animals, Cell Division, Cells, Cultured, Endothelium, Vascular, Flavonoids, Mitochondria, NAD, NADPH Dehydrogenase, Organophosphorus Compounds, Oxidation-Reduction, Phosphoproteins, Swine, Ubiquinone, Cell Hypoxia, Free Radical Scavengers, Oligonucleotides, Antisense, Reactive Oxygen Species, NADPH Oxidases, Mitogen-Activated Protein Kinase 1, MAP Kinase Signaling System, Membrane Transport Proteins
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