ArticleThe Journal of biological chemistry2014
Lipopolysaccharide-induced lung injury involves the nitration-mediated activation of RhoA.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
- RhoA through its various effectors mediate mitochondrial fragmentation in polycystic kidney disease.iScience · 2026Article
- Nitration in cancer signaling.Redox biology · 2026Review
- Toward Specific Detection of Peroxynitrite─Intramolecular Cyclization of Boronobenzylated Pyridinium Probe in Chemical and Cellular Systems.Chemical research in toxicology · 2026Article
- Immunomodulatory and anti-inflammatory potential of S-nitrosoglutathione (GSNO) in multiple sclerosis: a review of mechanisms and therapeutic perspectives.Frontiers in immunology · 2026Review
- The Critical Role of HMGB1Cys106 in Regulating Sex-Specific p53 Signaling in Pulmonary Arterial Hypertension.American journal of respiratory cell and molecular biology · 2025Article
- Nitration-driven structural changes in Hsp90 linked to gain of pathological functions.The Biochemical journal · 2025Article
- New insights on the regulators and inhibitors of RhoA-ROCK signalling in Parkinson's disease.Metabolic brain disease · 2025Review
- Inflammatory lung injury is associated with endothelial cell mitochondrial fission and requires the nitration of RhoA and cytoskeletal remodeling.Free radical biology & medicine · 2024Article
- Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.Cell communication and signaling : CCS · 2024Review
- Signaling pathways and potential therapeutic targets in acute respiratory distress syndrome (ARDS).Respiratory research · 2024Review
- A highly sensitive fluorescent probe RN-NA reveals peroxynitrite as a novel biomarker for primary open angle glaucoma.International journal of ophthalmology · 2024Article
- Calpain Promotes LPS-induced Lung Endothelial Barrier Dysfunction via Cleavage of Talin.American journal of respiratory cell and molecular biology · 2023Article
- Article
- Effects of SPA4 peptide on lipopolysaccharide-disrupted lung epithelial barrier, injury, and function in a human cell system and mouse model of lung injury.Physiological reports · 2022Article
- Cortactin loss protects against hemin-induced acute lung injury in sickle cell disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- RhoA Signaling in Neurodegenerative Diseases.Cells · 2022Review
- NF-κB-dependent repression of Sox18 transcription factor requires the epigenetic regulators histone deacetylases 1 and 2 in acute lung injury.Frontiers in physiology · 2022Article
- A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide.BMC molecular and cell biology · 2021Article
- Mechanosensitive cation channel Piezo1 contributes to ventilator-induced lung injury by activating RhoA/ROCK1 in rats.Respiratory research · 2021Article
- Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Acute lung injury (ALI) is characterized by increased endothelial hyperpermeability. Protein nitration is involved in the endothelial barrier dysfunction in LPS-exposed mice. However, the nitrated proteins involved in this process have not been identified. The activation of the small GTPase RhoA is a critical event in the barrier disruption associated with LPS. Thus, in this study we evaluated the possible role of RhoA nitration in this process. Mass spectroscopy identified a single nitration site, located at Tyr(34) in RhoA. Tyr(34) is located within the switch I region adjacent to the nucleotide-binding site. Utilizing this structure, we developed a peptide designated NipR1 (nitration inhibitory peptide for RhoA 1) to shield Tyr(34) against nitration. TAT-fused NipR1 attenuated RhoA nitration and barrier disruption in LPS-challenged human lung microvascular endothelial cells. Further, treatment of mice with NipR1 attenuated vessel leakage and inflammatory cell infiltration and preserved lung function in a mouse model of ALI. Molecular dynamics simulations suggested that the mechanism by which Tyr(34) nitration stimulates RhoA activity was through a decrease in GDP binding to the protein caused by a conformational change within a region of Switch I, mimicking the conformational shift observed when RhoA is bound to a guanine nucleotide exchange factor. Stopped flow kinetic analysis was used to confirm this prediction. Thus, we have identified a new mechanism of nitration-mediated RhoA activation involved in LPS-mediated endothelial barrier dysfunction and show the potential utility of "shielding" peptides to prevent RhoA nitration in the management of ALI.
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Registered trials
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