Regulation of vascular endothelial cell barrier function and cytoskeleton structure by protein phosphatases of the PPP family

2007 ◽  
Vol 293 (4) ◽  
pp. L843-L854 ◽  
Author(s):  
Csilla Csortos ◽  
Irina Kolosova ◽  
Alexander D. Verin
Keyword(s):  
Endothelial Cell ◽  
Barrier Function ◽  
Protein Phosphatases ◽  
Vascular Endothelial Cell ◽  
Cytoskeletal Proteins ◽  
Vascular Endothelial ◽  
Associated Proteins ◽  
Permeability Pulmonary Edema ◽  
Severe Lung

Reversible phosphorylation of cytoskeletal and cytoskeleton-associated proteins is a significant element of endothelial barrier function regulation. Therefore, understanding the mechanisms of phosphorylation/dephosphorylation of endothelial cell cytoskeletal proteins is vital to the treatment of severe lung disorders such as high permeability pulmonary edema. In vivo, there is a controlled balance between the activities of protein kinases and phosphatases. Due to various external or internal signals, this balance may be shifted. The actual balances at a given time alter the phosphorylation level of certain proteins with appropriate physiological consequences. The latest information about the structure and regulation of different types of Ser/Thr protein phosphatases participating in the regulation of endothelial cytoskeletal organization and barrier function will be reviewed here.

scholarly journals Suppressive Effects of GSS on Lipopolysaccharide-Induced Endothelial Cell Injury and ALI via TNF-α and IL-6

2019 ◽  
Vol 2019 ◽  
pp. 1-13 ◽  
Author(s):  
Lei Yi ◽  
Zengding Zhou ◽  
Yijuan Zheng ◽  
Mengling Chang ◽  
Xiaoqin Huang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Cell Injury ◽  
Inflammatory Mediator ◽  
Vascular Endothelial Cell ◽  
Vascular Endothelial ◽  
Promising Candidate ◽  
Neuroprotective Effects ◽  
Endothelial Cell Injury ◽  
Tnf Α

Background. Under septic conditions, LPS induced lung vascular endothelial cell (EC) injury, and the release of inflammatory mediator launches and aggravates acute lung injury (ALI). There are no effective therapeutic options for ALI. Genistein-3′-sodium sulfonate (GSS) is a derivative of native soy isoflavone, which exhibits neuroprotective effects via its antiapoptosis property. However, whether GSS protect against sepsis-induced EC injury and release of inflammatory mediators has not been determined. In this study, we found that GSS not only downregulated the levels of TNF-α and IL-6 in the lung and serum of mice in vivo but also inhibited the expression and secretion of TNF-α and IL-6 in ECs. Importantly, we also found that GSS blocked LPS-induced TNF-α and IL-6 expression in ECs via the Myd88/NF-κB signaling pathway. Taken together, our results demonstrated that GSS might be a promising candidate for sepsis-induced ALI via its regulating effects on inflammatory response in lung ECs.

CYLD regulates angiogenesis by mediating vascular endothelial cell migration

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4130-4137 ◽  
Author(s):  
Jinmin Gao ◽  
Lei Sun ◽  
Lihong Huo ◽  
Min Liu ◽  
Dengwen Li ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Vascular Endothelial Cells ◽  
Vascular Endothelial Cell ◽  
Tube Formation ◽  
Endothelial Cell Migration ◽  
Vascular Endothelial

Cylindromatosis (CYLD) is a deubiquitinase that was initially identified as a tumor suppressor and has recently been implicated in diverse normal physiologic processes. In this study, we have investigated the involvement of CYLD in angiogenesis, the formation of new blood vessels from preexisting ones. We find that knockdown of CYLD expression significantly impairs angiogenesis in vitro in both matrigel-based tube formation assay and collagen-based 3-dimensional capillary sprouting assay. Disruption of CYLD also remarkably inhibits angiogenic response in vivo, as evidenced by diminished blood vessel growth into the angioreactors implanted in mice. Mechanistic studies show that CYLD regulates angiogenesis by mediating the spreading and migration of vascular endothelial cells. Silencing of CYLD dramatically decreases microtubule dynamics in endothelial cells and inhibits endothelial cell migration by blocking the polarization process. Furthermore, we identify Rac1 activation as an important factor contributing to the action of CYLD in regulating endothelial cell migration and angiogenesis. Our findings thus uncover a previously unrecognized role for CYLD in the angiogenic process and provide a novel mechanism for Rac1 activation during endothelial cell migration and angiogenesis.

Effects of Pulsatile Flow on Cultured Vascular Endothelial Cell Morphology

1991 ◽  
Vol 113 (2) ◽  
pp. 123-131 ◽  
Author(s):  
G. Helmlinger ◽  
R. V. Geiger ◽  
S. Schreck ◽  
R. M. Nerem
Keyword(s):  
Shear Stress ◽  
Endothelial Cell ◽  
Pulsatile Flow ◽  
Cell Shape ◽  
Vascular Endothelial Cell ◽  
Shear Stresses ◽  
Type I ◽  
Vascular Endothelial ◽  
Type Ii

Endothelial cells (EC) appear to adapt their morphology and function to the in vivo hemodynamic environment in which they reside. In vitro experiments indicate that similar alterations occur for cultured EC exposed to a laminar steady-state flow-induced shear stress. However, in vivo EC are exposed to a pulsatile flow environment; thus, in this investigation, the influence of pulsatile flow on cell shape and orientation and on actin microfilament localization in confluent bovine aortic endothelial cell (BAEC) monolayers was studied using a 1-Hz nonreversing sinusoidal shear stress of 40 ± 20 dynes/cm2 (type I), 1-Hz reversing sinusoidal shear stresses of 20 ± 40 and 10 ± 15 dynes/cm2 (type II), and 1-Hz oscillatory shear stresses of 0 ± 20 and 0 ± 40 dynes/cm2 (type III). The results show that in a type I nonreversing flow, cell shape changed less rapidly, but cells took on a more elongated shape than their steady flow controls long-term. For low-amplitude type II reversing flow, BAECs changed less rapidly in shape and were always less elongated than their steady controls; however, for high amplitude reversal, BAECs did not stay attached for more than 24 hours. For type III oscillatory flows, BAEC cell shape remained polygonal as in static culture and did not exhibit actin stress fibers, such as occurred in all other flows. These results demonstrate that EC can discriminate between different types of pulsatile flow environments. Furthermore, these experiments indicate the importance of engineering the cell culture environment so as to include pulsatile flow in investigations of vascular endothelial cell biology, whether these studies are designed to study vascular biology and the role of the endothelial cell in disease processes, or are ones leading to the development of hybrid, endothelial cell-preseeded vascular grafts.

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