Cited by 295Metabolism, Diabetes, and CancerProtein Kinase Regulation and GTPase SignalingNitric Oxide and Endothelin Effects

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Activation and Signaling by the AMP-Activated Protein Kinase in Endothelial Cells

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Fisslthaler, Beate, Fleming, Ingrid·2009·Circulation Research

DOI 10.1161/circresaha.109.201590

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Abstract

The AMP-activated protein kinase (AMPK) was initially identified as the kinase that phosphorylates the 3-hydroxy 3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme for cholesterol biosynthesis. As the name suggests, the AMPK is activated by increased intracellular concentrations of AMP, and is generally described as a "metabolite-sensing kinase" and when activated initiates steps to conserve cellular energy. Although there is a strong link between the activity of the AMPK and metabolic control in muscle cells, the activity of the AMPK in endothelial cells can be regulated by stimuli that affect cellular ATP levels, such as hypoxia as well as by fluid shear stress, Ca(2+)-elevating agonists, and hormones such as adiponectin. To date the AMPK in endothelial cells has been implicated in the regulation of fatty acid oxidation, small G protein activity and nitric oxide production as well as inflammation and angiogenesis. Moreover, there is evidence indicating that the activation of the AMPK may help to prevent the vascular complications associated with the metabolic syndrome.

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7 retracted

Activation of the AMP-activated Protein Kinase by the Anti-diabetic Drug Metformin in Vivo
Zou, M., Kirkpatrick, S. S., Davis, B. J., Nelson, J. S., Wiles, W. G., Schlattner, U., Neumann, D., Brownlee, M., Freeman, M. B., & Goldman, M. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m404421200 · Cited by 480
Retracted
AMP-activated Protein Kinase Activity Is Critical for Hypoxia-inducible Factor-1 Transcriptional Activity and Its Target Gene Expression under Hypoxic Conditions in DU145 Cells
Lee, M. Y., Hwang, J.-T., Lee, H., Jung, S., Kang, I., Chi, S.-G., Kim, S. S., & Ha, J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306104200 · Cited by 234
Retracted
Upregulation of Mitochondrial Uncoupling Protein-2 by the AMP-Activated Protein Kinase in Endothelial Cells Attenuates Oxidative Stress in Diabetes
Xie, Z., Zhang, J., Wu, J., Viollet, B., & Zou, M. (2008) · Diabetes · doi:10.2337/db08-0610 · Cited by 165
Retracted
Glucose Deprivation Increases mRNA Stability of Vascular Endothelial Growth Factor through Activation of AMP-activated Protein Kinase in DU145 Prostate Carcinoma
Yun, H., Lee, M., Kim, S. S., & Ha, J. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m412994200 · Cited by 147
Retracted
Identification of Nitric Oxide as an Endogenous Activator of the AMP-activated Protein Kinase in Vascular Endothelial Cells
Zhang, J., Xie, Z., Dong, Y., Wang, S., Liu, C., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802578200 · Cited by 114
Retracted
Reactive Nitrogen Species Is Required for the Activation of the AMP-activated Protein Kinase by Statin in Vivo
Choi, H. C., Song, P., Xie, Z., Wu, Y., Xu, J., Zhang, M., Dong, Y., Wang, S., Lau, K., & Zou, M. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803020200 · Cited by 85
Retracted
Cilostazol inhibits cytokine-induced nuclear factor- B activation via AMP-activated protein kinase activation in vascular endothelial cells
Hattori, Y., Suzuki, K., Tomizawa, A., Hirama, N., Okayasu, T., Hattori, S., Satoh, H., Akimoto, K., & Kasai, K. (2008) · Cardiovascular Research · doi:10.1093/cvr/cvn226 · Cited by 59
Retracted
Resveratrol improves health and survival of mice on a high-calorie diet
Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., et al. (2006) · Nature · doi:10.1038/nature05354 · Cited by 4,290
TSC2 Mediates Cellular Energy Response to Control Cell Growth and Survival
Inoki, K., Zhu, T., & Guan, K.-L. (2003) · Cell · doi:10.1016/s0092-8674(03)00929-2 · Cited by 3,914
AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799

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10.1161/res.88.12.1276 · DOI
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10.1161/hyp.35.1.108 · DOI

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Authors: Fisslthaler, B., & Fleming, I.
Affiliations: Goethe University Frankfurt (DE)
ORCID: Fisslthaler, Beate
Fleming, Ingrid
Venue: Circulation Research
Publisher: Ovid Technologies (Wolters Kluwer Health)
Published: 2009-07-17
Volume: 105
Issue: 2
Pages: 114-127
ISSN: 0009-7330 (ISSN-L)
1524-4571
DOI: 10.1161/circresaha.109.201590
OpenAlex: W2117748926
Cited by: 295
References: 165
Citations by year: 2026: 4 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 17 · 2020: 15 · 2019: 14 · 2018: 18 · 2017: 14 · 2016: 22 · 2015: 27 · 2014: 20 · 2013: 22 · 2012: 29
FWCI: 2.29
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Circulation Research (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Keywords: AMPK, endothelial cells, AMPK signaling, energy sensing, hypoxia, fluid shear stress, adiponectin, fatty acid oxidation, small GTPases, nitric oxide production, inflammation, angiogenesis, metabolic syndrome, vascular complications
MeSH terms: Animals, Cardiovascular Diseases, Energy Metabolism, Enzyme Activation, Gene Expression Regulation, Homeostasis, Humans, Isoenzymes, Oxidation-Reduction, Phosphorylation, Signal Transduction, NADPH Oxidases, Enzyme Activators, Endothelial Cells, Protein Kinase Inhibitors, Proto-Oncogene Proteins c-akt, Nitric Oxide Synthase Type III, AMP-Activated Protein Kinases

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Activation and Signaling by the AMP-Activated Protein Kinase in Endothelial Cells

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