Roles of calcium, cyclic nucleotides, and protein kinase C in regulation of endothelial permeability.

Yamada, Yumiko; Furumichi, Takeo; Furui, Hirohiko; Yokoi, Taishi; Ito, Takahiko; Yamauchi, Kazunobu; Yokota, Mitsuhiro; Hayashi, Hiroshi; Saito, Hidehiko

doi:10.1161/01.atv.10.3.410

Cited by 64 publications

(32 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Since lead was found to alter PKC modulation in both endothelial and astroglial cells, its inhibitory effect on astroglial-induced endothelial differentiation may result from a primary influence on either astroglial inducer or endothelial effector cells (33). This is consistent with the ability of PKC agonists to activate endothelial cells (34,35) and dedifferentiate astroglial cells (36,37). Our findings suggest that lead damages brain microvessels by altering PKC modulation that results in endothelial dedifferentiation and blood-brain barrier dysfunction.…”

Section: Discussionsupporting

confidence: 78%

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Laterra¹,

Bressler²,

Indurti³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 78%

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Laterra¹,

Bressler²,

Indurti³

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…PKC activation has also been discussed to influence endothelial permeability, 21 but, to date, the results in HUVECs have been conflicting. Whereas Yamada et al 22 showed that activation of PKC caused a decrease in endothelial permeability, Bussolino et al 23 found an increase in endothelial permeability. As shown in Figure 3A, PMA stimulation of HUVECs did not result in increased VE-cadherin proteolysis, suggesting that ADAM10-mediated VE-cadherin processing is independent of PKC activation.…”

Section: Calcium Influx But Not Pkc Activation Induces Adam10-mediatementioning

confidence: 96%

ADAM10 Regulates Endothelial Permeability and T-Cell Transmigration by Proteolysis of Vascular Endothelial Cadherin

Schulz

Pruessmeyer²,

Maretzky³

et al. 2008

Circulation Research

263

257

View full text Add to dashboard Cite

Abstract-Vascular endothelial (VE)-cadherin is the major adhesion molecule of endothelial adherens junctions. It plays an essential role in controlling endothelial permeability, vascular integrity, leukocyte transmigration, and angiogenesis. Elevated levels of soluble VE-cadherin are associated with diseases like coronary atherosclerosis. Previous data showed that the extracellular domain of VE-cadherin is released by an unknown metalloprotease activity during apoptosis. In this study, we used gain-of-function analyses, inhibitor studies, and RNA interference experiments to analyze the proteolytic release of VE-cadherin in human umbilical vein endothelial cells (HUVECs). We found that VE-cadherin is specifically cleaved by the disintegrin and metalloprotease ADAM10 in its ectodomain, releasing a soluble fragment and generating a carboxyl-terminal membrane-bound stub, which is a substrate for a subsequent ␥-secretase cleavage. This ADAM10-mediated proteolysis could be induced by Ca 2ϩ influx and staurosporine treatment, indicating that ADAM10-mediated VE-cadherin cleavage contributes to the dissolution of adherens junctions during endothelial cell activation and apoptosis, respectively. In contrast, protein kinase C activation or inhibition did not modulate VE-cadherin processing. Increased ADAM10 expression was functionally associated with an increase in endothelial permeability. Remarkably, our data indicate that ADAM10 activity also contributes to the thrombin-induced decrease of endothelial cell-cell adhesion. Moreover, knockdown of ADAM10 in HUVECs as well as in T cells by small interfering RNA impaired T-cell transmigration. Taken together, our data identify ADAM10 as a novel regulator of vascular permeability and demonstrate a hitherto unknown function of ADAM10 in the regulation of VE-cadherindependent endothelial cell functions and leukocyte transendothelial migration. Key Words: endothelium Ⅲ metalloprotease Ⅲ endothelial permeability Ⅲ VE-cadherin T he endothelium represents the major physical barrier in the extravasation of blood components and leukocytes to the surrounding tissue. Impairment of this barrier by inflammatory mediators leads to disintegration of endothelial junctions and an increase in permeability and formation of edema. However, the molecular mechanisms regulating the cohesion of endothelial junctions are still poorly understood. Vascular endothelial (VE)-cadherin, which represents the major component of endothelial adherens junctions, is a crucial determinant of vascular integrity. This 130-kDa cell surface glycoprotein that mediates homotypic Ca 2ϩ -dependent cell adhesion also plays a central role in vasculogenesis, angiogenesis, and the regulation of macromolecular permeability. 1 Several inflammatory mediators and vasoactive factors, including thrombin, 2 have the potential to disrupt the VEcadherin complex and to increase vascular permeability providing the basis of edematous tissue injury in many diseases states including sepsis, ischemia/reperfusion, and acute respiratory dist...

show abstract

“…the recent finding that sodium nitroprusside decreased the permeability of albumin in monolayers of human endothelial cells (Yamada et al, 1990). Moreover, because 14C-sucrose crosses endothelial monolayers largely through endothelial junctions (Oliver, 1990), these results suggest that activation of soluble guanylate cyclase in endothelial monolayers grown on filters decreases the width of the endothelial junctions, perhaps due t o endothelial relaxation.…”

Section: ''And-sucrose Permeabilitymentioning

confidence: 64%

“…Protein kinase C activation constricts endothelial cells (Montesano and Orci, 1985) and increases endothelial permeability (Lynch et al, 1990;Oliver, 1990;Yamada et al, 1990). Because several ligands that activate protein kinase C in endothelial cells also enhance EDRF release (Peach et al, 19851, the released EDRF could attenuate the effect of protein kinase C activation on endothelial contraction and permeability.…”

Section: Discussionmentioning

confidence: 99%

“…These results indicate that L-arginine contributes to the sealing of the endothelial monolayer during basal in vitro conditions, likely by generating EDRF. cells (Montesano and Orci, 1985) and increases endothelial permeability (Lynch et al, 1990;Oliver, 1990;Yamada et al, 1990). For example, bradykinin constricts endothelial cells (Morel et al, 1989) and increases endothelial permeability (Murray et al, 1991) and EDRF synthesis (Chand and Altura, 1981).…”

Section: Effect Of Depletion Of L-arginine On 14c-sucrose Permeabilitmentioning

confidence: 99%

See 1 more Smart Citation

Endothelium‐derived relaxing factor contributes to the regulation of endothelial permeability

Oliver

1992

Journal Cellular Physiology

View full text Add to dashboard Cite

To determine whether endothelium-derived relaxing factor (EDRF) contributes to the regulation of endothelial permeability, the transendothelial flux of 14C-sucrose, a marker for the paracellular pathway across endothelial monolayers (Oliver, J. Cell. Physiol. 145:536-548, 1990), was examined in monolayers of bovine aortic endothelial cells grown on collagen-coated filters. The permeability coefficient of 14C-sucrose was significantly decreased by 10(-3) M 8-Bromoguanosine 3',5'-cyclic monophosphate or by 5 x 10(-6) M glyceryl trinitrate, an activator of soluble guanylate cyclase. Depletion of L-arginine from endothelial monolayers increased 14C-sucrose permeability from 3.21 +/- 0.59 to 3.88 +/- 0.50 x 10(-5) cm.sec-1 (mean +/- SEM; n = 6; P < 0.05). The acute administration of 5 x 10(-4) M L-arginine to monolayers depleted of this amino acid decreased 14C-sucrose permeability from 2.91 +/- 0.27 to 2.52 +/- 0.26 x 10(-5) cm.sec-1 (n = 11; P < 0.05). 14C-sucrose permeability was increased by 10(-7) M bradykinin and this effect was enhanced by the presence of each one of the following compounds: 10(-5) M methylene blue, 4 x 10(-6) M oxyhemoglobin, 5 x 10(-4) M NG-methyl-L-arginine or 5 x 10(-4) M N omega-nitro-L-arginine. These results suggest that EDRF contributes to the sealing of the endothelial monolayer and that EDRF released by bradykinin acts as a feedback inhibitor attenuating the increase in endothelial permeability induced by this peptide. Because endothelial cells have the ability to contract and relax and possess guanylate cyclase responsive to nitric oxide, our results suggest that EDRF decreases 14C-sucrose permeability by relaxing endothelial cells, thereby narrowing the width of endothelial junctions.

show abstract

Roles of calcium, cyclic nucleotides, and protein kinase C in regulation of endothelial permeability.

Cited by 64 publications

References 38 publications

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

Inhibition of astroglia-induced endothelial differentiation by inorganic lead: a role for protein kinase C.

ADAM10 Regulates Endothelial Permeability and T-Cell Transmigration by Proteolysis of Vascular Endothelial Cadherin

Endothelium‐derived relaxing factor contributes to the regulation of endothelial permeability

Contact Info

Product

Resources

About