ArticleMicrovascular research2010
Role of protein kinase Czeta in thrombin-induced RhoA activation and inter-endothelial gap formation of human dermal microvessel endothelial cell monolayers.
Article in Microvascular research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Regulation of blood-retinal barrier cell-junctions in diabetic retinopathy.Pharmacological research · 2020Review
- Synthesis and structure-activity relationships of thieno[2,3-d]pyrimidines as atypical protein kinase C inhibitors to control retinal vascular permeability and cytokine-induced edema.Bioorganic & medicinal chemistry · 2020Article
- Downregulation of S1P Lyase Improves Barrier Function in Human Cerebral Microvascular Endothelial Cells Following an Inflammatory Challenge.International journal of molecular sciences · 2020Article
- Protein Kinase Cθ Via Activating Transcription Factor 2-Mediated CD36 Expression and Foam Cell Formation of Ly6CCirculation · 2018Article
- Inhibition of Atypical Protein Kinase C Reduces Inflammation-Induced Retinal Vascular Permeability.The American journal of pathology · 2018Article
- A functional siRNA screen identifies RhoGTPase-associated genes involved in thrombin-induced endothelial permeability.PloS one · 2018Article
- IPCellular and molecular life sciences : CMLS · 2017Review
- Thrombin Induces Inositol Trisphosphate-Mediated Spatially Extensive Responses in Lung Microvessels.The American journal of pathology · 2017Article
- Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy.Oxidative medicine and cellular longevity · 2017Review
- Novel regulators of endothelial barrier function.American journal of physiology. Lung cellular and molecular physiology · 2014Review
- Mechanisms regulating endothelial permeability.Pulmonary circulation · 2014Review
- Reactive oxygen species in inflammation and tissue injury.Antioxidants & redox signaling · 2014Review
- Differential regulation of angiopoietin 1 and angiopoietin 2 during dengue virus infection of human umbilical vein endothelial cells: implications for endothelial hyperpermeability.Medical microbiology and immunology · 2013Article
- Ezrin/radixin/moesin proteins differentially regulate endothelial hyperpermeability after thrombin.American journal of physiology. Lung cellular and molecular physiology · 2013Article
- Using the past to inform the future: anti-VEGF therapy as a road map to develop novel therapies for diabetic retinopathy.Diabetes · 2013Article
- Synthesis and structure-activity relationships of 2-amino-3-carboxy-4-phenylthiophenes as novel atypical protein kinase C inhibitors.Bioorganic & medicinal chemistry letters · 2013Article
- Paeoniflorin attenuates lipopolysaccharide-induced permeability of endothelial cells: involvements of F-actin expression and phosphorylations of PI3K/Akt and PKC.Inflammation · 2013Article
- Phospholipase D signaling mediates reactive oxygen species-induced lung endothelial barrier dysfunction.Pulmonary circulation · 2013Article
- Novel atypical PKC inhibitors prevent vascular endothelial growth factor-induced blood-retinal barrier dysfunction.The Biochemical journal · 2012Article
- Hyperglycemia and endothelial dysfunction in atherosclerosis: lessons from type 1 diabetes.International journal of vascular medicine · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
We studied the potential involvement of the Ca(2+)-independent atypical protein kinase C isoform PKCzeta in mediating the thrombin-induced increase in endothelial permeability. Studies were done using human dermal microvessel endothelial cells (HMEC), which we showed constitutively expressed PKCzeta. We quantified the patency of inter-endothelial junctions (IEJs) and endothelial barrier function by measuring transendothelial electrical resistance (TER) in confluent HMEC monolayers. In control monolayers, thrombin decreased TER by approximately 50%, indicating thrombin-dependent opening of IEJs. Thrombin also elicited increases in cytosolic Ca(2+) concentration [Ca(2+)](i), actin stress fiber formation, and myosin light chain (MLC) phosphorylation. Pan-PKC inhibitors, calphostin C and chelerythrine, abrogated these responses. Thrombin also decreased TER after depletion of conventional and novel Ca(2+)-dependent PKC isoforms using phorbol 12-myristate 13-acetate (PMA). In these PMA-treated cells, thrombin induced inter-endothelial gap formation, MLC phosphorylation, and actin stress fiber formation, but failed to increase [Ca(2+)](i). Inhibition of PKCzeta activation using the PKCzeta pseudosubstrate peptide (PSI), depletion of PKCzeta protein with siRNA, and competitive inhibition of PKCzeta activity using dominant-negative (dn) PKCzeta mutant all prevented the thrombin-induced decrease in TER and MLC phosphorylation. Expression of dn-PKCzeta also inhibited thrombin-induced RhoA activation. These findings reveal a novel Ca(2+)-independent, PKCzeta-dependent mechanism of thrombin-induced increase in endothelial permeability. The results raise the possibility that inhibition of PKCzeta may be a novel drug target for thrombin-induced inflammatory hyperpermeability.
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