scholarly journals NF‑κB/IκBα signaling pathways are essential for resistance to heat stress‑induced ROS production in pulmonary microvascular endothelial cells

2021 ◽  
Vol 24 (5) ◽  
Author(s):  
Weidang Xie ◽  
Wei Huang ◽  
Shumin Cai ◽  
Hui Chen ◽  
Weijun Fu ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Heat Stress ◽  
Signaling Pathways ◽  
Microvascular Endothelial Cells ◽  
Ros Production ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Resistance To Heat

scholarly journals Membrane depolarization is the trigger for PI3K/Akt activation and leads to the generation of ROS

2012 ◽  
Vol 302 (1) ◽  
pp. H105-H114 ◽  
Author(s):  
Shampa Chatterjee ◽  
Elizabeth A. Browning ◽  
NanKang Hong ◽  
Kris DeBolt ◽  
Elena M. Sorokina ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Membrane ◽  
Fluid Shear Stress ◽  
Membrane Depolarization ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Ros Production ◽  
Akt Activation ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial

Loss of fluid shear stress (ischemia) to the lung endothelium causes endothelial plasma membrane depolarization via ATP-sensitive K+(KATP) channel closure, initiating a signaling cascade that leads to NADPH oxidase (NOX2) activation and ROS production. Since wortmannin treatment significantly reduces ROS production with ischemia, we investigated the role of phosphoinositide 3-kinase (PI3K) in shear-associated signaling. Pulmonary microvascular endothelial cells in perfused lungs subjected to abrupt stop of flow showed membrane depolarization and ROS generation. Stop of flow in flow-adapted mouse pulmonary microvascular endothelial cells in vitro resulted in the activation of PI3K and Akt as well as ROS generation. ROS generation in the lungs in situ was almost abolished by the PI3K inhibitor wortmannin and the PKC inhibitor H7. The combination of the two (wortmannin and H7) did not have a greater effect. Activation of NOX2 was greatly diminished by wortmannin, knockout of Akt1, or dominant negative PI3K, whereas membrane depolarization was unaffected. Ischemia-induced Akt activation (phosphorylation) was not observed with KATPchannel-null cells, which showed minimal changes in membrane potential with ischemia. Activation of Akt was similar to wild-type cells in NOX2-null cells, which do not generate ROS with ischemia. Cromakalim, a KATPchannel agonist, prevented both membrane depolarization and Akt phosphorylation with ischemia. Thus, Akt1 phosphorylation follows cell membrane depolarization and precedes the activation of NOX2. These results indicate that PI3K/Akt and PKC serve as mediators between endothelial cell membrane depolarization and NOX2 assembly.

Proproliferative phenotype of pulmonary microvascular endothelial cells

2007 ◽  
Vol 292 (3) ◽  
pp. L671-L677 ◽  
Author(s):  
Victor Solodushko ◽  
Brian Fouty
Keyword(s):  
Endothelial Cells ◽  
Barrier Function ◽  
Pulmonary Arteries ◽  
D1 Protein ◽  
Coagulation Cascade ◽  
Microvascular Endothelial Cells ◽  
Significant Heterogeneity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Pulmonary Microcirculation

Endothelial cells perform a number of important functions including release of vasodilators, control of the coagulation cascade, and restriction of solutes and fluid from the extravascular space. Regulation of fluid balance is of particular importance in the microcirculation of the lung where the loss of endothelial barrier function can lead to alveolar flooding and life-threatening hypoxemia. Significant heterogeneity exists between endothelial cells lining the microcirculation and cells from larger pulmonary arteries, however, and these differences may be relevant in restoring barrier function following vascular injury. Using well-defined populations of rat endothelial cells harvested from the pulmonary microcirculation [pulmonary microvascular endothelial cells (PMVEC)] and from larger pulmonary arteries [pulmonary artery endothelial cells (PAEC)], we compared their growth characteristics in low serum conditions. Withdrawal of serum inhibited proliferation and induced G0/G1 arrest in PAEC, whereas PMVEC failed to undergo G0/G1 arrest and continued to proliferate. Consistent with this observation, PMVEC had an increased cdk4 and cdk2 kinase activity with hyperphosphorylated (inactive) retinoblastoma (Rb) relative to PAEC as well as a threefold increase in cyclin D1 protein levels; overexpression of the cdk inhibitors p21Cip1/Waf1 and p27Kip1 induced G0/G1 arrest. While serum withdrawal failed to induce G0/G1 arrest in nonconfluent PMVEC, confluence was associated with hypophosphorylated Rb and growth arrest; loss of confluence led to resumption of growth. These data suggest that nonconfluent PMVEC continue to proliferate independently of growth factors. This proliferative characteristic may be important in restoring confluence (and barrier function) in the pulmonary microcirculation following endothelial injury.

Expression of simple epithelial cytokeratins in bovine pulmonary microvascular endothelial cells

1990 ◽  
Vol 143 (1) ◽  
pp. 140-149 ◽  
Author(s):  
Wayne F. Patton ◽  
Min Ung Yoon ◽  
J. Steven Alexander ◽  
Nancy Chung-Welch ◽  
Herbert B. Hechtman ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Microvascular Endothelial Cells ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Microvascular Endothelial

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

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