Lanthanum chloride causes blood–brain barrier disruption through intracellular calcium-mediated RhoA/Rho kinase signaling and myosin light chain kinase

Metallomics ◽  
2020 ◽  
Author(s):  
Jie Wu ◽  
Jinghua Yang ◽  
Miao Yu ◽  
Wenchang Sun ◽  
Yarao Han ◽  
...  
Keyword(s):  
Actin Cytoskeleton ◽  
Intracellular Calcium ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Endothelial Barrier ◽  
Blood Brain Barrier Disruption ◽  
Intracellular Ca ◽  
Brain Barrier Disruption

Lanthanum caused endothelial barrier hyperpermeability, loss of VE-cadherin and rearrangement of the actin cytoskeleton, though intracellular Ca2+-mediated RhoA/ROCK and MLCK pathways.

scholarly journals Human Blood-Brain Barrier Disruption by Retroviral-Infected Lymphocytes: Role of Myosin Light Chain Kinase in Endothelial Tight-Junction Disorganization

2007 ◽  
Vol 179 (4) ◽  
pp. 2576-2583 ◽  
Author(s):  
Philippe Vicente Afonso ◽  
Simona Ozden ◽  
Marie-Christine Prevost ◽  
Christine Schmitt ◽  
Danielle Seilhean ◽  
...  
Keyword(s):  
Tight Junction ◽  
Blood Brain Barrier ◽  
Light Chain ◽  
Human Blood ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Blood Brain Barrier Disruption ◽  
Brain Barrier Disruption ◽  
Endothelial Tight Junction

scholarly journals Thrombin-induced contraction in alveolar epithelial cells probed by traction microscopy

2006 ◽  
Vol 101 (2) ◽  
pp. 512-520 ◽  
Author(s):  
Núria Gavara ◽  
Raimon Sunyer ◽  
Pere Roca-Cusachs ◽  
Ramon Farré ◽  
Mar Rotger ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Actin Cytoskeleton ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Alveolar Epithelial Cells ◽  
Alveolar Epithelial ◽  
Contractile Forces ◽  
Traction Microscopy

Contractile tension of alveolar epithelial cells plays a major role in the force balance that regulates the structural integrity of the alveolar barrier. The aim of this work was to study thrombin-induced contractile forces of alveolar epithelial cells. A549 alveolar epithelial cells were challenged with thrombin, and time course of contractile forces was measured by traction microscopy. The cells exhibited basal contraction with total force magnitude 55.0 ± 12.0 nN (mean ± SE, n = 12). Traction forces were exerted predominantly at the cell periphery and pointed to the cell center. Thrombin (1 U/ml) induced a fast and sustained 2.5-fold increase in traction forces, which maintained peripheral and centripetal distribution. Actin fluorescent staining revealed F-actin polymerization and enhancement of peripheral actin rim. Disruption of actin cytoskeleton with cytochalasin D (5 μM, 30 min) and inhibition of myosin light chain kinase with ML-7 (10 μM, 30 min) and Rho kinase with Y-27632 (10 μM, 30 min) markedly depressed basal contractile tone and abolished thrombin-induced cell contraction. Therefore, the contractile response of alveolar epithelial cells to the inflammatory agonist thrombin was mediated by actin cytoskeleton remodeling and actomyosin activation through myosin light chain kinase and Rho kinase signaling pathways. Thrombin-induced contractile tension might further impair alveolar epithelial barrier integrity in the injured lung.

scholarly journals Inhibition of the myosin light chain kinase prevents hypoxia-induced blood-brain barrier disruption

2007 ◽  
Vol 102 (2) ◽  
pp. 501-507 ◽  
Author(s):  
Christoph R.W. Kuhlmann ◽  
Ryo Tamaki ◽  
Martin Gamerdinger ◽  
Volkmar Lessmann ◽  
Christian Behl ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Brain Barrier ◽  
Barrier Disruption ◽  
Blood Brain Barrier Disruption ◽  
Blood Brain ◽  
Brain Barrier Disruption

ROK contribution to endothelin-mediated contraction in aorta and mesenteric arteries following intermittent hypoxia/hypercapnia in rats

2007 ◽  
Vol 293 (5) ◽  
pp. H2911-H2918 ◽  
Author(s):  
Kyan J. Allahdadi ◽  
Benjimen R. Walker ◽  
Nancy L. Kanagy
Keyword(s):  
Arterial Pressure ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Intermittent Hypoxia ◽  
Myosin Light Chain ◽  
Mesenteric Arteries ◽  
Endothelin 1 ◽  
Second Messenger Systems ◽  
Intracellular Ca ◽  
Inner Diameter

We reported previously that intermittent hypoxia with CO2 to maintain eucapnia (IH-C) elevates plasma endothelin-1 (ET-1) and arterial pressure. In small mesenteric arteries (sMA; inner diameter = 150 μm), IH-C augments ET-1 constrictor sensitivity but diminishes ET-1-induced increases in intracellular Ca2+ concentration, suggesting IH-C exposure increases both ET-1 levels and ET-1-stimulated Ca2+ sensitization. Because Rho-associated kinase (ROK) can mediate Ca2+ sensitization, we hypothesized that augmented vasoconstrictor sensitivity to ET-1 in arteries from IH-C-exposed rats is dependent on ROK activation. In thoracic aortic rings, ET-1 contraction was not different between groups, but ROK inhibition (Y-27632, 3 and 10 μM) attenuated ET-1 contraction more in IH-C than in sham arteries (50 ± 11 and 78 ± 7% vs. 41 ± 12 and 48 ± 9% inhibition, respectively). Therefore, ROK appears to contribute more to ET-1 contraction in IH-C than in sham aorta. In sMA, ROK inhibitors did not affect ET-1-mediated constriction in sham arteries and only modestly inhibited it in IH-C arteries. In ionomycin-permeabilized sMA with intracellular Ca2+ concentration held at basal levels, Y-27632 did not affect ET-1-mediated constriction in either IH-C or sham sMA and ET-1 did not stimulate ROK translocation. In contrast, inhibition of myosin light-chain kinase (ML-9, 100 μM) prevented ET-1-mediated constriction in sMA from both groups. Therefore, IH-C exposure increases ET-1 vasoconstrictor sensitivity in sMA but not in aorta. Furthermore, ET-1 constriction is myosin light-chain kinase dependent and mediated by Ca2+ sensitization that is independent of ROK activation in sMA but not aorta. Thus ET-1-mediated signaling in aorta and sMA is altered by IH-C but is dependent on different second messenger systems in small vs. large arteries.

scholarly journals Myosin light chain kinase regulates cell polarization independently of membrane tension or Rho kinase

2015 ◽  
Vol 209 (2) ◽  
pp. 275-288 ◽  
Author(s):  
Sunny S. Lou ◽  
Alba Diz-Muñoz ◽  
Orion D. Weiner ◽  
Daniel A. Fletcher ◽  
Julie A. Theriot
Keyword(s):  
Cell Polarity ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Model System ◽  
Cell Polarization ◽  
Membrane Tension ◽  
Specific Mechanism

Cells polarize to a single front and rear to achieve rapid actin-based motility, but the mechanisms preventing the formation of multiple fronts are unclear. We developed embryonic zebrafish keratocytes as a model system for investigating establishment of a single axis. We observed that, although keratocytes from 2 d postfertilization (dpf) embryos resembled canonical fan-shaped keratocytes, keratocytes from 4 dpf embryos often formed multiple protrusions despite unchanged membrane tension. Using genomic, genetic, and pharmacological approaches, we determined that the multiple-protrusion phenotype was primarily due to increased myosin light chain kinase (MLCK) expression. MLCK activity influences cell polarity by increasing myosin accumulation in lamellipodia, which locally decreases protrusion lifetime, limiting lamellipodial size and allowing for multiple protrusions to coexist within the context of membrane tension limiting protrusion globally. In contrast, Rho kinase (ROCK) regulates myosin accumulation at the cell rear and does not determine protrusion size. These results suggest a novel MLCK-specific mechanism for controlling cell polarity via regulation of myosin activity in protrusions.

Rat pulmonary arterial smooth muscle myosin light chain kinase and phosphatase activities decrease with age

2006 ◽  
Vol 290 (3) ◽  
pp. L509-L516 ◽  
Author(s):  
J. Belik ◽  
Ewa Kerc ◽  
Mary D. Pato
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Adult Tissue ◽  
Adult Rat ◽  
Pulmonary Arterial ◽  
Pulmonary Arterial Smooth Muscle ◽  
Specific Activities

We and others have shown that the fetal pulmonary arterial smooth muscle potential for contraction and relaxation is significantly reduced compared with the adult. Whether these developmental changes relate to age differences in the expression and/or activity of key enzymes regulating the smooth muscle mechanical properties has not been previously evaluated. Therefore, we studied the catalytic activities and expression of myosin light chain kinase (MLCK) and myosin light chain phosphatase (MLCP) catalytic (PP1cδ) and regulatory (MYPT) subunits in late fetal, early newborn, and adult rat intrapulmonary arterial tissues. In keeping with the greater force development and relaxation of adult pulmonary artery, Western blot analysis showed that the MLCK, MYPT, and PP1cδ contents increased significantly with age and were highest in the adult rat. In contrast, their specific activities (activity/enzyme content) were significantly higher in the fetal compared with the adult tissue. The fetal and newborn pulmonary arterial muscle relaxant response to the Rho-kinase inhibitor Y-27632 was greater than the adult tissue. In addition to the 130-kDa isoform of MLCK, we documented the presence of minor higher-molecular-weight embryonic isoforms in the fetus and newborn. During fetal life, the lung pulmonary arterial MLCK- and MLCP-specific activities are highest and appear to be related to Rho-kinase activation during lung morphogenesis.

373 Role of myosin light chain kinase and Rho kinase in carbachol-induced contractions of human detrusor smooth muscle

2012 ◽  
Vol 11 (1) ◽  
pp. e373
Author(s):  
C. Protzel ◽  
T. Kirschstein ◽  
K. Porath ◽  
T. Sellmann ◽  
R. Koehling ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Detrusor Smooth Muscle ◽  
Human Detrusor
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