ArticleJournal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics2010
Lovastatin inhibits the thrombin-induced loss of barrier integrity in bovine corneal endothelium.
Article in Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 15 citations in OpenAlex.
- Establishment of the deuterium oxide dilution method as a new possibility for determining the transendothelial water permeability.Pflugers Archiv : European journal of physiology · 2024Article
- Is There a Relationship between Statin Use and Corneal Specular Microscopy and Topography Findings?Beyoglu eye journal · 2021Article
- Elevated cytokines, thrombin and PAI-1 in severe HCPS patients due to Sin Nombre virus.Viruses · 2015Article
- Inhibition of Rho and Rac geranylgeranylation by atorvastatin is critical for preservation of endothelial junction integrity.PloS one · 2013Article
- Establishment of inducible wild type and mutant myocilin-GFP-expressing RGC5 cell lines.PloS one · 2012Article
- Barrier stabilizing mediators in regulation of microvascular endothelial permeability.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2012Review
- Elevated cAMP opposes (TNF-alpha)-induced loss in the barrier integrity of corneal endothelium.Molecular vision · 2010Article
- Dynamic regulation of barrier integrity of the corneal endothelium.Optometry and vision science : official publication of the American Academy of Optometry · 2010Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
purposeIncreased actomyosin contraction of the dense band of actin cytoskeleton at the apical junctional complex (perijunctional actomyosin ring, PAMR) breaks down the barrier integrity of corneal endothelium. This study has investigated the efficacy of statins, which inhibit activation of RhoA, in opposing the thrombin-induced loss of barrier integrity of monolayers of cultured bovine corneal endothelium.
methodsMyosin light chain (MLC) phosphorylation, a biochemical measure of actomyosin contraction, was assayed by urea-glycerol gel electrophoresis, followed by western blot analysis. The locus of MLC phosphorylation and changes in the organization of the PAMR were visualized by immunostaining. Phosphorylation of MYPT1, a regulatory subunit of myosin light-chain phosphatase (MLCP), was assessed by Western blot analysis to determine down-regulation of RhoA. The barrier integrity was assessed in terms of trans-endothelial electrical resistance (TER), and further confirmed by determining permeability to FITC dextran (10 kDa) and distribution of ZO-1, a marker of tight junctional assembly.
resultsLovastatin, a prototype of lipophilic statins, induced MLC dephosphorylation under basal conditions. It opposed increase in phosphorylation of MLC and MYPT1 in response to thrombin and nocodazole, agents known to activate RhoA in the endothelium. Pretreatment with the statin opposed the thrombin- and nocodazole-induced disruption of the PAMR and the thrombin-induced decline in TER. Lovastatin also opposed the thrombin- and nocodazole-induced increase in permeability to FITC dextran and redistribution of ZO-1. However, upon supplementation with GGPP (geranylgeranyl pyrophosphate), lovastatin failed to oppose the effects of thrombin and nocodazole on the PAMR, ppMLC, and ZO-1 distribution.
conclusionsLovastatin attenuates RhoA activation in the corneal endothelium presumably by reducing its isoprenylation. This underlies the suppression of the thrombin-induced loss in barrier integrity of the corneal endothelium.
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