The DOI matches its Crossref record; 34 of the 34 references it cites were found in a registry or an index.
Induction of Endothelial NO Synthase by Hydrogen Peroxide via a Ca 2+ /Calmodulin-Dependent Protein Kinase II/Janus Kinase 2–Dependent Pathway
Open accessAbstract
We have recently demonstrated that hydrogen peroxide (H 2 O 2 ) is an extremely potent stimulus of endothelial NO synthase (eNOS) gene expression. The present study was designed to identify the signaling mechanisms mediating this response. Induction of eNOS expression by H 2 O 2 was found to be Ca 2+ dependent, inasmuch as it was blocked by BAPTA-AM. Further studies have indicated that Ca 2+ /calmodulin-dependent protein kinase II (CaM kinase II) plays a critical role in mediating this response. Immunocytochemical staining with an anti-CaM kinase II antibody confirmed the expression of CaM kinase II in cultured bovine aortic endothelial cells. H 2 O 2 induced autophosphorylation of CaM kinase II and increased the activity of the enzyme, as assessed by an in-gel kinase assay. A specific inhibitor for CaM kinase II, KN93, and a calmodulin antagonist, W-7, attenuated eNOS induction by H 2 O 2 . Further studies have indicated that janus kinase 2 is important in mediating increased eNOS expression in response to H 2 O 2 and likely is downstream from CaM kinase II. In conclusion, these data provide the first evidence that CaM kinase II plays a critical role in endothelial redox signaling. Regulation of eNOS via this pathway may represent an important vascular adaptation to oxidant stress.
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“The signaling mechanisms of hydrogen peroxide in ECs (941) lead to the increased activity of eNOS and other enzymes (121, 141, 193, 251, 815, 940).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [141]
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Cites
Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress
Cai, H., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.87.10.840 · Cited by 3,839
Self-citationEpidermal Growth Factor (EGF)-induced Generation of Hydrogen Peroxide
Bae, Y. S., Kang, S. W., Seo, M. S., Baines, I., Tekle, E., Chock, P. B., & Rhee, S. G. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.1.217 · Cited by 1,208
NEURONAL Ca2+/CALMODULIN-DEPENDENT PROTEIN KINASES
Hanson, P. I., & Schulman, H. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.003015 · Cited by 728
Activation of protein kinase C by tyrosine phosphorylation in response to H 2 O 2
Konishi, H., Tanaka, M., Takemura, Y., Matsuzaki, H., Ono, Y., Kikkawa, U., & Nishizuka, Y. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.21.11233 · Cited by 604
Activation of the JAK-STAT pathway by reactive oxygen species
Simon, A. R., Rai, U., Fanburg, B. L., & Cochran, B. (1998) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1998.275.6.c1640 · Cited by 597
Ushio‐Fukai, M., Alexander, R. W., Akers, M., Yin, Q., Fujio, Y., Walsh, K., & Griendling, K. K. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.32.22699 · Cited by 558
CaM kinase signaling induces cardiac hypertrophy and activates the MEF2 transcription factor in vivo
Passier, R., Zeng, H., Frey, N., Naya, F. J., Nicol, R. L., McKinsey, T. A., Overbeek, P. A., Richardson, J. A., Grant, S. R., & Olson, E. N. (2000) · Journal of Clinical Investigation · doi:10.1172/jci8551 · Cited by 521
Phosphorylation of Endothelial Nitric Oxide Synthase in Response to Fluid Shear Stress
Corson, M. A., James, N. L., Latta, S. E., Nerem, R. M., Berk, B. C., & Harrison, D. G. (1996) · Circulation Research · doi:10.1161/01.res.79.5.984 · Cited by 521
Self-citationInteractions of oxidants with vascular signaling systems
Wolin, M. S. (2000) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.20.6.1430 · Cited by 463
Drummond, G. R., Cai, H., Davis, M. E., Ramasamy, S., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.86.3.347 · Cited by 430
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Role of Oxidative Modifications in Atherosclerosis
Stocker, R., & Keaney, J. F. (2004) · Physiological Reviews · doi:10.1152/physrev.00047.2003 · Cited by 2,651
Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase
Fleming, I., & Busse, R. (2003) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00323.2002 · Cited by 941
Hydrogen peroxide regulation of endothelial function: Origins, mechanisms, and consequences
Cai, H. “. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2005.06.021 · Cited by 571
Self-citationSources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Balligand, J.-L., Feron, O., & Dessy, C. (2009) · Physiological Reviews · doi:10.1152/physrev.00042.2007 · Cited by 477
Metadata
- Authors
- Cai, H., Davis, M. E., Drummond, G. R., & Harrison, D. G.
- Affiliations
- Emory University (US)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2001-10
- Volume
- 21
- Issue
- 10
- Pages
- 1571-1576
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2040801242
- Cited by
- 160
- References
- 34
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 8 · 2023: 4 · 2022: 3 · 2021: 5 · 2020: 3 · 2019: 1 · 2018: 2 · 2017: 3 · 2016: 8 · 2015: 6 · 2014: 5 · 2013: 8 · 2012: 14
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- National Institutes of Health (5r01hl059248-04)
- National Heart, Lung, and Blood Institute (HL 58000, HL 59248, HL 39000 6, P01HL058000)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Keywords
- endothelial nitric oxide synthase, hydrogen peroxide, calcium/calmodulin-dependent protein kinase II, JAK2, oxidative stress, eNOS gene expression, autophosphorylation, calmodulin, KN-93, W-7, bovine aortic endothelial cells
- MeSH terms
- Benzenesulfonamides, Animals, Benzylamines, Calcium, Cattle, Cells, Cultured, Endothelium, Vascular, Enzyme Inhibitors, Hydrogen Peroxide, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, RNA, Messenger, Sulfonamides, Signal Transduction, Transcriptional Activation, Calcium-Calmodulin-Dependent Protein Kinases, Nitric Oxide Synthase, Nitric Oxide Synthase Type III, Janus Kinase 2, Calcium-Calmodulin-Dependent Protein Kinase Type 2
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