ArticleThe Journal of biological chemistry2010
Calcium/Calmodulin-dependent protein kinase II delta 6 (CaMKIIdelta6) and RhoA involvement in thrombin-induced endothelial barrier dysfunction.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
33 citing papers in PubMed, 59 citations in OpenAlex.
- The role and therapeutic potential of purinergic signaling pathway in metabolic syndrome-related atherosclerosis.Purinergic signalling · 2026Review
- Dual-Omics Mapping of Tinnitus Phenotype Transition in Noise-Exposed Auditory Cortex.Cellular and molecular neurobiology · 2025Article
- Benzene metabolites increase vascular permeability by activating heat shock proteins and Rho GTPases.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Gut Microbes Secretions May Trigger Mononuclear Cell Migration and Offer Comorbidity Mechanism Between Inflammatory Bowel Disease and Diabetic Retinopathy.Mediators of inflammation · 2025Article
- Quantitative proteomics reveals CLR interactome in primary human cells.The Journal of biological chemistry · 2024Article
- Diosmetin alleviates acute lung injury caused by lipopolysaccharide by targeting barrier function.Inflammopharmacology · 2023Article
- Activation of NMDA receptors in brain endothelial cells increases transcellular permeability.Fluids and barriers of the CNS · 2022Article
- Article
- CaMKIIδ is upregulated by pro-inflammatory cytokine IL-6 in a JAK/STAT3-dependent manner to promote angiogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Spatiotemporal restriction of endothelial cell calcium signaling is required during leukocyte transmigration.The Journal of experimental medicine · 2021Article
- CaMKIIδ Splice Variants in the Healthy and Diseased Heart.Frontiers in cell and developmental biology · 2021Review
- P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- Endothelial Cell Calcium Signaling during Barrier Function and Inflammation.The American journal of pathology · 2020Review
- IPCellular and molecular life sciences : CMLS · 2017Review
- Extracellular heat shock protein 90α mediates HDM-induced bronchial epithelial barrier dysfunction by activating RhoA/MLC signaling.Respiratory research · 2017Article
- Article
- Calcium Signaling Is Dispensable for Receptor Regulation of Endothelial Barrier Function.The Journal of biological chemistry · 2016Article
- Vascular CaMKII: heart and brain in your arteries.American journal of physiology. Cell physiology · 2016Review
- Multiple CaMKII Binding Modes to the Actin Cytoskeleton Revealed by Single-Molecule Imaging.Biophysical journal · 2016Article
- Pitfalls in assessing microvascular endothelial barrier function: impedance-based devices versus the classic macromolecular tracer assay.Scientific reports · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Multiple Ca(2+) release and entry mechanisms and potential cytoskeletal targets have been implicated in vascular endothelial barrier dysfunction; however, the immediate downstream effectors of Ca(2+) signals in the regulation of endothelial permeability still remain unclear. In the present study, we evaluated the contribution of multifunctional Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) as a mediator of thrombin-stimulated increases in human umbilical vein endothelial cell (HUVEC) monolayer permeability. For the first time, we identified the CaMKIIdelta(6) isoform as the predominant CaMKII isoform expressed in endothelium. As little as 2.5 nM thrombin maximally increased CaMKIIdelta(6) activation assessed by Thr(287) autophosphorylation. Electroporation of siRNA targeting endogenous CaMKIIdelta (siCaMKIIdelta) suppressed expression of the kinase by >80% and significantly inhibited 2.5 nM thrombin-induced increases in monolayer permeability assessed by electrical cell-substrate impedance sensing (ECIS). siCaMKIIdelta inhibited 2.5 nM thrombin-induced activation of RhoA, but had no effect on thrombin-induced ERK1/2 activation. Although Rho kinase inhibition strongly suppressed thrombin-induced HUVEC hyperpermeability, inhibiting ERK1/2 activation had no effect. In contrast to previous reports, these results indicate that thrombin-induced ERK1/2 activation in endothelial cells is not mediated by CaMKII and is not involved in endothelial barrier hyperpermeability. Instead, CaMKIIdelta(6) mediates thrombin-induced HUVEC barrier dysfunction through RhoA/Rho kinase as downstream intermediates. Moreover, the relative contribution of the CaMKIIdelta(6)/RhoA pathway(s) diminished with increasing thrombin stimulation, indicating recruitment of alternative signaling pathways mediating endothelial barrier dysfunction, dependent upon thrombin concentration.
Indexed as
Identifiers
What OpenQuestion holds
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 OpenQuestion graph.