ArticleScientific reports2021
Essential role for paxillin tyrosine phosphorylation in LPS-induced mitochondrial fission, ROS generation and lung endothelial barrier loss.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- Albumin Restores Endothelial Cell Mitochondrial Morphology in Patients With Decompensated Cirrhosis.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Endothelial mitochondrial homeostasis in the development and progression of atherosclerosis.Frontiers in cardiovascular medicine · 2026Review
- [Resveratrol protects barrier function of mouse brain microvascular endothelial cell monolayers with oxygen/glucose deprivation and PMNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Single-cell transcriptomics of neuroinflammation and cerebrovascular endothelial cells in the aged rat hippocampus.iScience · 2025Article
- Mechanometabolism: recent findings on the intersection of cell adhesion, cell migration, and metabolism.American journal of physiology. Cell physiology · 2025Review
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- Investigating the neuroprotective effect of heparin in improving mitochondrial function in rats with cardiac arrest cardiopulmonary resuscitation based on transcriptome sequencing.Frontiers in medicine · 2025Article
- Mechanisms of oxidative stress-induced sperm dysfunction.Frontiers in endocrinology · 2025Review
- Endothelial knockdown of the tumor suppressor,American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Mitochondrial Dysfunction: A Roadmap for Understanding and Tackling Cardiovascular Aging.Aging and disease · 2024Review
- Novel Morphological Profiling Assay ConnectsGastro hep advances · 2024Article
- The bisphosphonates alendronate and zoledronate induce adaptations of aerobic metabolism in permanent human endothelial cells.Scientific reports · 2023Article
- Absence of TRIC-B from type XIV Osteogenesis Imperfecta osteoblasts alters cell adhesion and mitochondrial function - A multi-omics study.Matrix biology : journal of the International Society for Matrix Biology · 2023Article
- Injured Endothelial Cell: A Risk Factor for Pulmonary Fibrosis.International journal of molecular sciences · 2023Review
- CeONanomaterials (Basel, Switzerland) · 2023Article
- [ALDH2 attenuates LPS-induced increase of brain microvascular endothelial cell permeability by promoting fusion and inhibiting fission of the mitochondria].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2022Article
- TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- Role of Lysocardiolipin Acyltransferase in Cigarette Smoke-Induced Lung Epithelial Cell Mitochondrial ROS, Mitochondrial Dynamics, and Apoptosis.Cell biochemistry and biophysics · 2022Article
- Systemic Effects of mitoTEMPO upon Lipopolysaccharide Challenge Are Due to Its Antioxidant Part, While Local Effects in the Lung Are Due to Triphenylphosphonium.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
We have shown that both reactive oxygen species (ROS) and paxillin tyrosine phosphorylation regulate LPS-induced human lung endothelial permeability. Mitochondrial ROS (mtROS) is known to increase endothelial cell (EC) permeability which requires dynamic change in mitochondrial morphology, events that are likely to be regulated by paxillin. Here, we investigated the role of paxillin and its tyrosine phosphorylation in regulating LPS-induced mitochondrial dynamics, mtROS production and human lung microvascular EC (HLMVEC) dysfunction. LPS, in a time-dependent manner, induced higher levels of ROS generation in the mitochondria compared to cytoplasm or nucleus. Down-regulation of paxillin expression with siRNA or ecto-expression of paxillin Y31F or Y118F mutant plasmids attenuated LPS-induced mtROS in HLMVECs. Pre-treatment with MitoTEMPO, a scavenger of mtROS, attenuated LPS-induced mtROS, endothelial permeability and VE-cadherin phosphorylation. Further, LPS-induced mitochondrial fission in HLMVECs was attenuated by both a paxillin siRNA, and paxillin Y31F/Y118F mutant. LPS stimulated phosphorylation of dynamin-related protein (DRP1) at S616, which was also attenuated by paxillin siRNA, and paxillinY31/Y118 mutants. Inhibition of DRP1 phosphorylation by P110 attenuated LPS-induced mtROS and endothelial permeability. LPS challenge of HLMVECs enhanced interaction between paxillin, ERK, and DRP1, and inhibition of ERK1/2 activation with PD98059 blocked mitochondrial fission. Taken together, these results suggest a key role for paxillin tyrosine phosphorylation in LPS-induced mitochondrial fission, mtROS generation and EC barrier dysfunction.
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Registered trials
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 Socratic graph.