Cited by 428Nitric Oxide and Endothelin EffectsRedox biology and oxidative stressNeutrophil, Myeloperoxidase and Oxidative Mechanisms

Poldip2, a Novel Regulator of Nox4 and Cytoskeletal Integrity in Vascular Smooth Muscle Cells

Open access
Lyle, Alicia N., Deshpande, Nita N., Taniyama, Yoshihiro, Seidel-Rogol, Bonnie, Pounkova, Lily, Du, Pingfeng, Papaharalambus, Christopher, Lassègue, Bernard +1 more·2009·Circulation Research

Abstract

Rationale: NADPH oxidases (Noxes) regulate vascular physiology and contribute to the pathogenesis of vascular disease. In vascular smooth muscle cells (VSMCs), the interactions of individual Nox homologs with regulatory proteins are poorly defined. Objective: The objective of this study was to identify novel NADPH oxidase regulatory proteins. Methods and Results: Using a yeast 2-hybrid screen, we identified a novel p22phox binding partner, Poldip2, and demonstrated that it associates with p22phox, NADPH oxidase (Nox)1, and Nox4 and colocalizes with p22phox at sites of Nox4 localization. Poldip2 increases Nox4 enzymatic activity by 3-fold and positively regulates basal reactive oxygen species production in VSMCs (O 2 ·− : 86.3±15.6% increase; H 2 O 2 : 40.7±4.5% increase). Overexpression of Poldip2 activates Rho (180.2±24.8% increase), strengthens focal adhesions, and increases stress fiber formation. These phenotypic changes are blocked by dominant negative Rho. In contrast, depletion of either Poldip2 or Nox4 results in a loss of these structures, which is rescued by adding back active Rho. Cell migration, which requires dynamic cytoskeletal remodeling, is impaired by either excess (70.1±14.7% decrease) or insufficient Poldip2 (63.5±5.9% decrease). Conclusions: These results suggest that Poldip2 associates with p22phox to activate Nox4, leading to regulation of focal adhesion turnover and VSMC migration, thus linking reactive oxygen species production and cytoskeletal remodeling. Poldip2 may be a novel therapeutic target for vascular pathologies with a significant VSMC migratory component, such as restenosis and atherosclerosis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1161/circresaha.109.193722

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

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?

  • More recent observations indicate that the ADMA/l-arginine ratios in plasma may be a better marker than either metabolite assessed independently.

    “More recent observations indicate that the ADMA/l-arginine ratios in plasma may be a better marker than either metabolite assessed independently (75, 589, 606, 790, 966).”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Lyle, A. N., Deshpande, N. N., Taniyama, Y., Seidel-Rogol, B., Pounkova, L., Du, P., Papaharalambus, C., Lassègue, B., & Griendling, K. K.
Affiliations
  • Emory University (US)
  • From the Department of Medicine (A.N.L., N.N.D., B.S.-R., L.P., P.D., C.P., B.L., K.K.G.), Division of Cardiology, Emory University School of Medicine, Atlanta, Ga. Present address for Y.T.: Department of Vascular and Geriatric Medicine, Kinki University School of Medicine, Osaka, Japan.
Venue
Circulation Research
Published
2009-07-31
Volume
105
Issue
3
Pages
249-259
ISSN
  • 0009-7330 (ISSN-L)
  • 1524-4571
OpenAlex
W2118193478
Cited by
428
References
41
Citations by year
2026: 3 · 2025: 11 · 2024: 14 · 2023: 19 · 2022: 19 · 2021: 14 · 2020: 18 · 2019: 30 · 2018: 25 · 2017: 24 · 2016: 34 · 2015: 20 · 2014: 44 · 2013: 50 · 2012: 45
FWCI
22.75
Type
journal article
Language
en
Open access
Locations
  • Circulation Research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • American Heart Association
  • National Institutes of Health
  • National Heart, Lung, and Blood Institute (HL38206, R01HL038206, R37HL038206, HL05863, R01HL058863)
  • National Institute of General Medical Sciences (T32GM008602)
Topics
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
  • Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
Keywords
Poldip2, NOX4, NADPH oxidase, p22phox, vascular smooth muscle cells, reactive oxygen species, RhoA, focal adhesions, stress fibers, cytoskeletal remodeling, cell migration
MeSH terms
NADPH Oxidase 4, Animals, Carrier Proteins, Cell Movement, Cells, Cultured, Cytoskeleton, Humans, Muscle, Smooth, Vascular, Nuclear Proteins, Oxidation-Reduction, Saccharomyces cerevisiae, Reactive Oxygen Species, Cell Cycle Proteins, NADPH Oxidases, rhoA GTP-Binding Protein, Rats

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