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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“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]
Citations
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302
Chandel, N. S., McClintock, D. S., Feliciano, C. E., Wood, T. M., Melendez, J. A., Rodriguez, A. M., & Schumacker, P. T. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m001914200 · Cited by 2,000
Mitochondrial reactive oxygen species trigger hypoxia-induced transcription
Chandel, N. S., Maltepe, E., Goldwasser, E., Mathieu, C. E., Simon, M. C., & Schumacker, P. T. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.20.11715 · Cited by 1,926
Generation of reactive oxygen species by the mitochondrial electron transport chain
Liu, Y., Fiskum, G., & Schubert, D. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2002.00744.x · Cited by 1,260
Selective Targeting of a Redox-active Ubiquinone to Mitochondria within Cells
Kelso, G. F., Porteous, C. M., Coulter, C. V., Hughes, G., Porteous, W. K., Ledgerwood, E. C., Smith, R. A. J., & Murphy, M. P. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009093200 · Cited by 1,091
Oosthuyse, B., Moons, L., Storkebaum, E., Beck, H., Nuyens, D., Brusselmans, K., Dorpe, J. V., Hellings, P., Gorselink, M., Heymans, S., et al. (2001) · Nature Genetics · doi:10.1038/88842 · Cited by 1,007
Hwang, P. M., Bunz, F., Yu, J., Rago, C., Chan, T. A.-T., Murphy, M. P., Kelso, G. F., Smith, R. A. J., Kinzler, K. W., & Vogelstein, B. (2001) · Nature Medicine · doi:10.1038/nm1001-1111 · Cited by 430
Baas, A. S., & Berk, B. C. (1995) · Circulation Research · doi:10.1161/01.res.77.1.29 · Cited by 415
Colavitti, R., Pani, G., Bedogni, B., Anzevino, R., Borrello, S., Waltenberger, J. L., & Galeotti, T. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107711200 · Cited by 389
Cellular oxygen sensing by mitochondria: old questions, new insight
Chandel, N. S., & Schumacker, P. T. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.5.1880 · Cited by 389
Cited by
Sorted by citations
Items 101–127 of 127
Nazari, A., Osati, P., Fakhr, S. S., Faghihkhorasani, F., Ghanaatian, M., Faghihkhorasani, F., Rezaei‐Tazangi, F., Far, N. P., Shourideh, A., Ebrahimi, N., et al. (2024) · Antioxidants and Redox Signaling · doi:10.1089/ars.2023.0491 · Cited by 13
Holmén, B. A., Rukavina, B., Kasumba, J., & Fukagawa, N. K. (2017) · Energy & Fuels · doi:10.1021/acs.energyfuels.7b00698 · Cited by 13
Hypoxia-Induced Mitochondrial ROS and Function in Pulmonary Arterial Endothelial Cells
Wang, H., Song, T., Reyes-García, J., & Wang, Y.-X. (2024) · Cells · doi:10.3390/cells13211807 · Cited by 11
Hypoxia reduces endothelial Ang1-induced Tie2 activity in a Tie1-dependent manner
Yun, J.-H., Lee, H. M., Lee, E. H., Park, J., & Cho, C. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.06.018 · Cited by 10
Marcuzzi, A., Piscianz, E., Loganes, C., Brumatti, L. V., Knowles, A., Bilel, S., Tommasini, A., Bortul, R., & Zweyer, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms17010047 · Cited by 11
Oxidants and Endothelial Dysfunction
Lund, A. K. (2010) · Elsevier eBooks · doi:10.1016/b978-0-08-046884-6.00712-0 · Cited by 12
Retinal Physiology and Circulation: Effect of Diabetes
Wright, W. S., Eshaq, R. S., Lee, M., Kaur, G., & Harris, N. R. (2020) · Comprehensive physiology · doi:10.1002/j.2040-4603.2020.tb00135.x · Cited by 9
Reactive Oxygen Species (ROS) Signaling in Cardiac Remodeling and Failure
Harvey, A., & Grieve, D. (2014) · Springer eBooks · doi:10.1007/978-3-642-30018-9_50 · Cited by 9
Vosseler, M., Abegunewardene, N., Hoffmann, N., Petersen, S. E., Becker, D., Cleppien, D., Kunz, W. S., Kreitner, K.-F., Lauterbach, M., Bierbach, B., et al. (2009) · European Surgical Research · doi:10.1159/000211716 · Cited by 8
Moore, K. F., Polidori, A., & Sioutas, C. (2011) · Cited by 7
Targeting Antioxidants to Mitochondria by Conjugation to Lipophilic
Murphy, M. P., & Smith, R. A. J. (2007) · Cited by 5
Alhobeira, H. A. (2020) · Bioinformation · doi:10.6026/97320630016789 · Cited by 6
Oxidants and Endothelial Dysfunction
Lund, A. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.65250-9 · Cited by 6
Riedinger, H., Eger, F., Trummler, K., & PROBST, H. (2005) · Biochemical Journal · doi:10.1042/bj20040492 · Cited by 5
Effects of Alpha-Lipoic Acid on AMP-Activated Protein Kinase in Different Tissues
Lee, K., Koh, E. H., Kim, M.-S., Park, J., & Cho, E. H. (2008) · Oxidative stress and disease · doi:10.1201/9781420045390.ch21 · Cited by 4
Parra, A. Q., Jaimes, J. H. G., & Vargas, M. J. Q. (2012) · Redalyc (Universidad Autónoma del Estado de México) · doi:10.24054/01204211.v1.n1.2012.46 · Cited by 2
Paulson, S. E. (2016) · Cited by 2
Oxidants and Endothelial Dysfunction
Lund, A. K. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-95488-4.00071-1 · Cited by 2
NADPH Oxidases and Blood-Brain Barrier Dysfunction in Stroke
Kahles, T., Heumüller-Klug, S., & Brandes, R. P. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-600-9_11 · Cited by 2
Mitogen-Activated Protein Kinase and Natural Phenolic Compounds in Cardiovascular Remodeling
Alam, M. A., Uddin, S. J., & Brown, L. (2012) · Studies in natural products chemistry · doi:10.1016/b978-0-444-59530-0.00006-x · Cited by 2
Ossum, C. G., Lauritsen, A. N., Karottki, D. G., & Hoffmann, E. K. (2011) · Cellular Physiology and Biochemistry · doi:10.1159/000325213 · Cited by 2
Manganese Superoxide Dismutase (MnSOD) and Its Importance in Mitochondrial Function and Cancer
Holley, A. K., & Clair, D. K. S. (2016) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-3-319-30705-3_3 · Cited by 2
Mitochondria-targeted antioxidants: coenzyme Q10, mito-Q and beyond
López‐Lluch, G. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-90256-4.00013-8 · Cited by 1
Reactive Oxygen Species and Atherosclerosis
Víctor, V. M. (2014) · Springer eBooks · doi:10.1007/978-3-642-30018-9_53 · Cited by 1
cell survival in endothelial cells Transient hypoxia induces ERK-dependent anti-apoptotic
Piper, H. M., Noll, T., Härtel, F. V., Holl, M., Arshad, M., Aslam, M., Gündüz, D., & Weyand, M. (2016)
Self-citationHypoxia Decreases Mitochondrial ROS Production in CellsPreprint
Sen, B., Benoit, B., & Brand, M. D. (2024) · SSRN Electronic Journal · doi:10.2139/ssrn.4876726
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
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
