Cited by 127Redox biology and oxidative stressNitric Oxide and Endothelin EffectsAngiogenesis and VEGF in Cancer

Role of Redox Signaling in the Autonomous Proliferative Response of Endothelial Cells to Hypoxia

Schäfer, M., Schäfer, C., Ewald, N., Piper, H.M., Noll, Th.·2003·Circulation Research

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.

Integrity signals

Registry

Crossref · 10.1161/01.res.0000070882.81508.fc

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • 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.

    “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).”

Cites

Flagged first, then by citations

Cited by

Sorted by citations

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 › 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

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review