ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2012
Oxidation of HRas cysteine thiols by metabolic stress prevents palmitoylation in vivo and contributes to endothelial cell apoptosis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- Reactive Oxygen Species Mechanisms that Regulate Protein-Protein Interactions in Cancer.International journal of molecular sciences · 2024Review
- A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95.Life science alliance · 2023Article
- Regulation of Ras Signaling by S-Nitrosylation.Antioxidants (Basel, Switzerland) · 2023Review
- Review
- Identification of the hub genes related to adipose tissue metabolism of bovine.Frontiers in veterinary science · 2022Article
- Palm Oil-Rich Diet Affects Murine Liver Proteome andInternational journal of molecular sciences · 2021Article
- Review
- Pleiotropic and Potentially Beneficial Effects of Reactive Oxygen Species on the Intracellular Signaling Pathways in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2021Review
- Lipid-induced S-palmitoylation as a Vital Regulator of Cell Signaling and Disease Development.International journal of biological sciences · 2021Review
- Redox RegulationAntioxidants & redox signaling · 2020Review
- Palmitoylation: A Fatty Regulator of Myocardial Electrophysiology.Frontiers in physiology · 2020Review
- Cysteine-based regulation of redox-sensitive Ras small GTPases.Redox biology · 2019Review
- Target Identification of Active Constituents ofFrontiers in pharmacology · 2019Article
- Systematic and Quantitative Assessment of Hydrogen Peroxide Reactivity With Cysteines Across Human Proteomes.Molecular & cellular proteomics : MCP · 2017Article
- Subcellular Distribution of S-Nitrosylated H-Ras in Differentiated and Undifferentiated PC12 Cells during Hypoxia.Cell journal · 2017Article
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2017Article
- Sirtuin 1 regulates cardiac electrical activity by deacetylating the cardiac sodium channel.Nature medicine · 2017Article
- Chemical proteomics reveals ADP-ribosylation of small GTPases during oxidative stress.Nature chemical biology · 2017Article
- The redox mechanism for vascular barrier dysfunction associated with metabolic disorders: Glutathionylation of Rac1 in endothelial cells.Redox biology · 2016Article
- The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.Molecular neurobiology · 2016Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Here we demonstrate a new paradigm in redox signaling, whereby oxidants resulting from metabolic stress directly alter protein palmitoylation by oxidizing reactive cysteine thiolates. In mice fed a high-fat, high-sucrose diet and in cultured endothelial cells (ECs) treated with high palmitate and high glucose (HPHG), there was decreased HRas palmitoylation on Cys181/184 (61±24% decrease for cardiac tissue and 38±7.0% in ECs). This was due to oxidation of Cys181/184, detected using matrix-assisted laser desorption/ionization time of flight (MALDI TOF)-TOF. Decrease in HRas palmitoylation affected its compartmentalization and Ras binding domain binding activity, with a shift from plasma membrane tethering to Golgi localization. Loss of plasma membrane-bound HRas decreased growth factor-stimulated ERK phosphorylation (84±8.6% decrease) and increased apoptotic signaling (24±6.5-fold increase) after HPHG treatment that was prevented by overexpressing wild-type but not C181/184S HRas. The essential role of HRas in metabolic stress was made evident by the similar effects of expressing an inactive dominant negative N17-HRas or a MEK inhibitor. Furthermore, the relevance of thiol oxidation was demonstrated by overexpressing manganese superoxide dismutase, which improved HRas palmitoylation and ERK phosphorylation, while lessening apoptosis in HPHG treated ECs.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.