scholarly journals Role of caveolin-1 in the regulation of the vascular shear stress response

2006 ◽  
Vol 116 (5) ◽  
pp. 1222-1225 ◽  
Author(s):  
P. G. Frank
Keyword(s):  
Shear Stress ◽  
Stress Response ◽  
Caveolin 1 ◽  
Shear Stress Response

scholarly journals Shear stress augments mitochondrial ATP generation that triggers ATP release and Ca2+ signaling in vascular endothelial cells

2018 ◽  
Vol 315 (5) ◽  
pp. H1477-H1485 ◽  
Author(s):  
Kimiko Yamamoto ◽  
Hiromi Imamura ◽  
Joji Ando
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular Endothelial Cells ◽  
Critical Role ◽  
Atp Release ◽  
Vascular Endothelial ◽  
The Novel ◽  
Caveolin 1 ◽  
Atp Generation

Vascular endothelial cells (ECs) sense and transduce hemodynamic shear stress into intracellular biochemical signals, and Ca2+ signaling plays a critical role in this mechanotransduction, i.e., ECs release ATP in the caveolae in response to shear stress and, in turn, the released ATP activates P2 purinoceptors, which results in an influx into the cells of extracellular Ca2+. However, the mechanism by which the shear stress evokes ATP release remains unclear. Here, we demonstrated that cellular mitochondria play a critical role in this process. Cultured human pulmonary artery ECs were exposed to controlled levels of shear stress in a flow-loading device, and changes in the mitochondrial ATP levels were examined by real-time imaging using a fluorescence resonance energy transfer-based ATP biosensor. Immediately upon exposure of the cells to flow, mitochondrial ATP levels increased, which was both reversible and dependent on the intensity of shear stress. Inhibitors of the mitochondrial electron transport chain and ATP synthase as well as knockdown of caveolin-1, a major structural protein of the caveolae, abolished the shear stress-induced mitochondrial ATP generation, resulting in the loss of ATP release and influx of Ca2+ into the cells. These results suggest the novel role of mitochondria in transducing shear stress into ATP generation: ATP generation leads to ATP release in the caveolae, triggering purinergic Ca2+ signaling. Thus, exposure of ECs to shear stress seems to activate mitochondrial ATP generation through caveola- or caveolin-1-mediated mechanisms. NEW & NOTEWORTHY The mechanism of how vascular endothelial cells sense shear stress generated by blood flow and transduce it into functional responses remains unclear. Real-time imaging of mitochondrial ATP demonstrated the novel role of endothelial mitochondria as mechanosignaling organelles that are able to transduce shear stress into ATP generation, triggering ATP release and purinoceptor-mediated Ca2+ signaling within the cells.

Modeling shear stress response of bituminous materials under small and large strains

2020 ◽  
Vol 252 ◽  
pp. 119133 ◽  
Author(s):  
Aboelkasim Diab ◽  
Zhanping You ◽  
Sanjeev Adhikari ◽  
Xuelian Li
Keyword(s):  
Shear Stress ◽  
Stress Response ◽  
Large Strains ◽  
Bituminous Materials ◽  
Shear Stress Response

Integrin mechanotransduction stimulates caveolin-1 phosphorylation and recruitment of Csk to mediate actin reorganization

2005 ◽  
Vol 288 (2) ◽  
pp. H936-H945 ◽  
Author(s):  
C. Radel ◽  
V. Rizzo
Keyword(s):  
Shear Stress ◽  
Dependent Manner ◽  
Laminar Shear Stress ◽  
Integrin Activation ◽  
Actin Reorganization ◽  
Aortic Endothelial Cells ◽  
Caveolin 1 ◽  
Domain Peptide ◽  
Mlc Phosphorylation

To identify the role of caveolin-1 in integrin mechanotransduction, we exposed bovine aortic endothelial cells to 10 dyn/cm2 of laminar shear stress. Caveolin-1 was acutely and transiently phosphorylated with shear, occurring downstream of β1-integrin activation as the β1-integrin blocking antibody JB1A was inhibitory. In manipulating Src family kinase (SFK) activity with knockdown of Csk or type 1 protein phosphatase (PP1) treatment, we observed coordinate increase and decrease in shear-induced caveolin-1 phosphorylation, respectively. Hence, shear-stimulated caveolin-1 phosphorylation is regulated by SFKs. Shear-induced recruitment and phosphorylation of caveolin-1 occurred at β1-integrin sites in a β1-integrin- and SFK-dependent manner. Csk, described to interact with pY14-caveolin-1 and integrins, bound to an increased pool of phosphorylated caveolin-1 after shear corresponding with elevated Csk at β1-integrin sites. Like caveolin-1, treatment with JB1A and PP1 attenuated shear-induced Csk association with β1-integrins. Csk function was assayed with transfection of a caveolin-1 phosphorylation domain peptide. The peptide attenuated shear-induced association of Csk at β1-integrin sites, as well as colocalization of Csk with paxillin and phosphorylated caveolin-1. Because integrin and Csk activity regulate cytoskeletal reorganization, we evaluated the role of this mechanism in shear-induced myosin light chain (MLC) phosphorylation. Knockdown of Csk expression was sufficient to reduce MLC diphosphorylation due to shear. Disruption of Csk-integrin association by peptide treatment was also inhibitory of the MLC diphosphorylation response. Together these data indicate that integrin activation with shear stress results in SFK-regulated caveolin-1 phosphorylation that, in turn, mediates Csk association at integrin sites, where it plays a role in downstream, shear-stimulated MLC diphosphorylation.

scholarly journals Endothelial basement membrane laminin 511 is essential for shear stress response

2016 ◽  
Vol 36 (2) ◽  
pp. 183-201 ◽  
Author(s):  
Jacopo Di Russo ◽  
Anna‐Liisa Luik ◽  
Lema Yousif ◽  
Sigmund Budny ◽  
Hans Oberleithner ◽  
...  
Keyword(s):  
Shear Stress ◽  
Stress Response ◽  
Basement Membrane ◽  
Endothelial Basement Membrane ◽  
Shear Stress Response
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