ArticleProceedings of the National Academy of Sciences of the United States of America2009
Endothelial nitric oxide synthase negatively regulates hydrogen peroxide-stimulated AMP-activated protein kinase in endothelial cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
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- Eosinophil Peroxidase Catalyzed Protein Carbamylation Participates in Asthma.The Journal of biological chemistry · 2016Article
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- Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: the role of mitochondria.Journal of cellular and molecular medicine · 2014Article
- Caveolin-1 is a critical determinant of autophagy, metabolic switching, and oxidative stress in vascular endothelium.PloS one · 2014Article
- Epigallocatechin gallate (EGCG) stimulates autophagy in vascular endothelial cells: a potential role for reducing lipid accumulation.The Journal of biological chemistry · 2013Article
- Mitochondrial oxidative stress corrupts coronary collateral growth by activating adenosine monophosphate activated kinase-α signaling.Arteriosclerosis, thrombosis, and vascular biology · 2013Article
- Angiotensin II impairs endothelial nitric-oxide synthase bioavailability under free cholesterol-enriched conditions via intracellular free cholesterol-rich membrane microdomains.The Journal of biological chemistry · 2013Article
- Article
- Nitric oxide in skeletal muscle: role on mitochondrial biogenesis and function.International journal of molecular sciences · 2012Review
- MARCKS protein mediates hydrogen peroxide regulation of endothelial permeability.Proceedings of the National Academy of Sciences of the United States of America · 2012Article
- Angiotensin-II and MARCKS: a hydrogen peroxide- and RAC1-dependent signaling pathway in vascular endothelium.The Journal of biological chemistry · 2012Article
- Acute exposure to low glucose rapidly induces endothelial dysfunction and mitochondrial oxidative stress: role for AMP kinase.Arteriosclerosis, thrombosis, and vascular biology · 2012Article
- Hydrogen peroxide differentially modulates cardiac myocyte nitric oxide synthesis.Proceedings of the National Academy of Sciences of the United States of America · 2011Article
- Article
- Regulation of SIRT1 in cellular functions: role of polyphenols.Archives of biochemistry and biophysics · 2010Review
Corrections and comments
- Erratum issued
Authors and funding
4 authors at 3 institutions in 3 countries.
Funding
Abstract
Hydrogen peroxide and other reactive oxygen species are intimately involved in endothelial cell signaling. In many cell types, the AMP-activated protein kinase (AMPK) has been implicated in the control of metabolic responses, but the role of endothelial cell redox signaling in the modulation of AMPK remains to be completely defined. We used RNA interference and pharmacological methods to establish that H(2)O(2) is a critical activator of AMPK in cultured bovine aortic endothelial cells (BAECs). H(2)O(2) treatment of BAECs rapidly and significantly increases the phosphorylation of AMPK. The EC(50) for H(2)O(2)-promoted phosphorylation of AMPK is 65 + or - 15 microM, within the physiological range of cellular H(2)O(2) concentrations. The Ca(2+)/calmodulin-dependent protein kinase kinase-beta (CaMKKbeta) inhibitor STO-609 abolishes H(2)O(2)-dependent AMPK activation, whereas eNOS inhibitors enhance AMPK activation. Similarly, siRNA-mediated knockdown of CaMKKbeta abrogates AMPK activation, whereas siRNA-mediated knockdown of eNOS leads to a striking increase in AMPK phosphorylation. Cellular imaging studies using the H(2)O(2) biosensor HyPer show that siRNA-mediated eNOS knockdown leads to a marked increase in intracellular H(2)O(2) generation, which is blocked by PEG-catalase. eNOS(-/-) mice show a marked increase in AMPK phosphorylation in liver and lung compared to wild-type mice. Lung endothelial cells from eNOS(-/-) mice also show a significant increase in AMPK phosphorylation. Taken together, these results establish that CaMKKbeta is critically involved in mediating the phosphorylation of AMPK promoted by H(2)O(2) in endothelial cells, and document that eNOS is an important negative regulator of AMPK phosphorylation and intracellular H(2)O(2) generation in endothelial cells.
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Registered trials
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