Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Zhou, Xiaoyan; Wen, Ke; Dong, Yixin; Ai, Ling; He, Pingnian

doi:10.1152/ajpheart.01037.2008

Cited by 14 publications

(24 citation statements)

References 37 publications

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“…The ROS-induced barrier dysfunction has been studied in endothelial cells. Previous studies suggest that ROS-mediated permeability changes in endothelial cells involve activation of protein kinase C [Siflinger-Birnboim et al, 1992], Src kinase [Shi et al, 2000], Rho/Rho kinase pathway [Sanchez et al, 2007], and calcium influx [Zhou et al, 2009]. U0126 is a highly specific inhibitor of MEK1/2.…”

Section: Discussionmentioning

confidence: 99%

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Peng

Lin

Chen

et al. 2012

J of Cellular Biochemistry

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Uremic patients have a much higher risk of cardiovascular diseases and death. Uremic toxins are probably involved in the development of vascular endothelial dysfunction. Indoxyl sulfate (IS) is a uremic toxin that accumulates with deterioration of renal function. This study explored the effects of IS on the adherens junctions of vascular endothelial cells and revealed the underlying mechanism. Bovine pulmonary artery endothelial cells (BPAECs) were treated with IS, and the distribution of vascular endothelial cadherin (VE-cadherin), p120-catenin, β-catenin, and stress fibers was examined by immunofluorescence. IS treatment resulted in disruption of intercellular contacts between BPAECs with prominent parallel-oriented intracellular stress fiber formation. Intracellular free radical levels which measured by flow cytometry increased after IS treatment. The antioxidant, MnTMPyP, and an ERK pathway inhibitor, U0126, both significantly prevented IS-induced disruption of intercellular contacts. Western blotting analyses demonstrated that IS-induced phosphorylation of myosin light chain kinase (MLCK) and myosin light chains (MLC) as well as activation of extracellular-signal-regulated protein kinase (ERK1/ERK2). Pretreatment with MnTMPyP prevented ERK1/2 phosphorylation. U0126 prevented the IS-induced MLCK and MLC phosphorylation. MEK-ERK acted as the upstream regulator of the MLCK-MLC pathway. These findings suggest that the superoxide anion-MEK-ERK-MLCK-MLC signaling mediates IS-induced junctional dispersal of BPAECs.

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Section: Discussionmentioning

confidence: 99%

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Peng

Lin

Chen

et al. 2012

J of Cellular Biochemistry

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“…This receptor subtype-specific Ca 2ϩ response can be cell type dependent. For example, JTE-013, a selective S1P R2 antagonist, inhibited the S1P-induced Ca 2ϩ response in smooth muscle cells but failed to affect S1P-induced Ca 2ϩ mobilization in human umbilical vein endothelial cells (28 release (13,46). Currently, the reported sources of S1P-induced Ca 2ϩ mobilization in cultured cells are not consistent (23,28).…”

Section: Discussionmentioning

confidence: 99%

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Zhang

Qian

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

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Zhang G, Xu S, Qian Y, He P. Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules. Am J Physiol Heart Circ Physiol 299: H1494 -H1504, 2010. First published August 20, 2010 doi:10.1152/ajpheart.00462.2010.-Sphingosine-1-phosphate (S1P) has been demonstrated to enhance endothelial barrier function in vivo and in vitro. However, different S1P receptor subtypes have been indicated to play different or even opposing roles in the regulation of vascular barrier function. This study aims to differentiate the roles of endogenous endothelial S1P subtype receptors in the regulation of permeability in intact microvessels using specific receptor agonist and antagonists. Microvessel permeability was measured with hydraulic conductivity (Lp) in individually perfused rat mesenteric venules. S1P-mediated changes in endothelial intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) was measured in fura-2-loaded venules. Confocal images of fluorescent immunostaining illustrated the spatial expressions of three S1P subtype receptors (S1PR1-3) in rat venules. The application of S1P (1 M) in the presence of S1P R1-3 inhibited platelet-activating factor-or bradykinin-induced permeability increase. This S1P effect was reversed only with a selective S1PR1 antagonist, W-146, and was not affected by S1PR2 or S1PR3 antagonists JTE-013 and CAY-10444, respectively. S1PR1 was also identified as the sole receptor responsible for S1P-mediated increases in endothelial [Ca 2ϩ ]i. S1PR2 or S1PR3 antagonist alone affected neither basal Lp nor platelet-activating factor-induced permeability increase. The selective S1P R1 agonist, SEW-2871, showed similar [Ca 2ϩ ]i and permeability effect to that of S1P. These results indicate that, despite the presence of S1PR1-3 in the intact venules, only the activation of endothelial S1P R1 is responsible for the protective action of S1P on microvessel permeability and that endogenous S1PR2 or S1PR3 did not exhibit functional roles in the regulation of permeability under basal or acutely stimulated conditions. sphingosine-1-phosphate receptors; microvessel permeability; sphingosine-1-phosphate subtype receptor expression; endothelial calcium concentration AN INFLAMMATORY MEDIATOR-INDUCED increase in microvascular permeability, mainly occurring at postcapillary venules, is a critical event, resulting in edema formation, organ dysfunction, and the pathogenesis of many cardiovascular diseases. The increased microvessel permeability-associated endothelial gap formation also serves as the initiating step for the activation of platelets and leukocytes, resulting in platelet/leukocyte aggregate formation and augmented increases in microvessel permeability (12). Identifying an effective strategy to enhance endothelial barrier function and prevent permeability increases is critical for combating a variety of cardiovascular diseases.Sphingosine-1-phosphate (S1P), a biologically active lipid mediator, has been identified as an important regulat...

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“…MetaFluor software (Universal Imaging) was used for image acquisition and data analyses. Details have been described elsewhere (42,43).…”

Section: Methodsmentioning

confidence: 99%

“…2) have been previously described (42). To evaluate the correlation of endothelial [Ca 2ϩ ]i with NO at the cellular level (data shown in Fig.…”

Section: Methodsmentioning

confidence: 99%

“…These studies demonstrated a magnitude correlation between PAF-induced increases in endothelial intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ), NO production, and microvessel permeability at the single vessel level. At the individual endothelial cell level, previous studies (23,26,42) in venular microvessels demonstrated that endothelial [Ca 2ϩ ] i does not uniformly increase in response to proinflammatory agents or a Ca 2ϩ ionophore. The ionomycin-induced macromolecule leakages were most prominent at sites where the averaged increase in endothelial [Ca 2ϩ ] i from a group of cells was the largest (26).…”

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confidence: 99%

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Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca²⁺]_i, nitric oxide, and gap formation in intact venules

Zhou

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Zhou X, He P. Temporal and spatial correlation of plateletactivating factor-induced increases in endothelial [Ca 2ϩ ]i, nitric oxide, and gap formation in intact venules. Am J Physiol Heart Circ Physiol 301: H1788 -H1797, 2011. First published August 26, 2011 doi:10.1152/ajpheart.00599.2011We have previously demonstrated that platelet-activating factor (PAF)-induced increases in microvessel permeability were associated with endothelial gap formation and that the magnitude of peak endothelial intracellular Ca 2ϩ concentration ([Ca 2ϩ ]i) and nitric oxide (NO) production at the single vessel level determines the degree of the permeability increase. This study aimed to examine whether the magnitudes of PAF-induced peak endothelial [Ca 2ϩ ]i, NO production, and gap formation are correlated at the individual endothelial cell level in intact rat mesenteric venules. Endothelial gaps were quantified by the accumulation of fluorescent microspheres at endothelial clefts using confocal imaging. Endothelial [Ca 2ϩ ]i was measured on fura-2-or fluo-4-loaded vessels, and 4,5-diaminofluorescein (DAF-2) was used for NO measurements. The results showed that increases in endothelial [Ca 2ϩ ]i, NO production, and gap formation occurred in all endothelial cells when vessels were exposed to PAF but manifested a spatial heterogeneity in magnitudes among cells in each vessel. PAF-induced peak endothelial [Ca 2ϩ ]i preceded the peak NO production by 0.6 min at the cellular level, and the magnitudes of NO production and gap formation linearly correlated with that of the peak endothelial [Ca 2ϩ ]i in each cell, suggesting that the initial levels of endothelial [Ca 2ϩ ]i determine downstream NO production and gap formation. These results provide direct evidence from intact venules that inflammatory mediator-induced increases in microvessel permeability are associated with the generalized formation of endothelial gaps around all endothelial cells. The spatial differences in the molecular signaling that were initiated by the heterogeneous endothelial Ca 2ϩ response contribute to the heterogeneity in permeability increases along the microvessel wall during inflammation. microvessel permeability; endothelial Ca 2ϩ imaging; nitric oxide imaging; endothelial junctions; intracellular Ca 2ϩ concentration INCREASED MICROVESSEL PERMEABILITY to fluid and macromolecules is a hallmark of inflammation, resulting in edema formation and organ dysfunctions. A better understanding of the mechanisms that regulate microvessel permeability will benefit the development of potential therapeutic strategies for inflammation-related diseases. Gap formation between endothelial cells has been indicated as the main transport pathway responsible for the increased permeability to fluid and macromolecules during inflammation (3,6,15,17,18,22,24,29). Our previous study (17) demonstrated that the dynamic changes in endothelial gaps upon platelet-activating factor (PAF) stimulation closely correlated with the time course of increases in microvessel hydraul...

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Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Cited by 14 publications

References 37 publications

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca²⁺]_i, nitric oxide, and gap formation in intact venules

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Calcium influx-dependent differential actions of superoxide and hydrogen peroxide on microvessel permeability

Cited by 14 publications

References 37 publications

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Effects of indoxyl sulfate on adherens junctions of endothelial cells and the underlying signaling mechanism

Sphingosine-1-phosphate prevents permeability increases via activation of endothelial sphingosine-1-phosphate receptor 1 in rat venules

Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca2+]i, nitric oxide, and gap formation in intact venules

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Temporal and spatial correlation of platelet-activating factor-induced increases in endothelial [Ca²⁺]_i, nitric oxide, and gap formation in intact venules