scholarly journals Early Alterations of Bile Canaliculi Dynamics and the Rho Kinase/Myosin Light Chain Kinase Pathway Are Characteristics of Drug-Induced Intrahepatic Cholestasis

2016 ◽  
Vol 44 (11) ◽  
pp. 1780-1793 ◽  
Author(s):  
M. G. Burbank ◽  
A. Burban ◽  
A. Sharanek ◽  
R. J. Weaver ◽  
C. Guguen-Guillouzo ◽  
...  
Keyword(s):  
Light Chain ◽  
Intrahepatic Cholestasis ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Bile Canaliculi ◽  
Drug Induced ◽  
Kinase Pathway

scholarly journals Rho-kinase/myosin light chain kinase pathway plays a key role in the impairment of bile canaliculi dynamics induced by cholestatic drugs

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Ahmad Sharanek ◽  
Audrey Burban ◽  
Matthew Burbank ◽  
Rémy Le Guevel ◽  
Ruoya Li ◽  
...  
Keyword(s):  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Rho Kinase ◽  
Bile Canaliculi ◽  
Kinase Pathway

Pressor responses to platelet-activating factor and thromboxane are mediated by Rho-kinase

2004 ◽  
Vol 287 (1) ◽  
pp. L250-L257 ◽  
Author(s):  
C. Martin ◽  
R. Göggel ◽  
A.-R. Ressmeyer ◽  
S. Uhlig
Keyword(s):  
Smooth Muscle ◽  
Light Chain ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Kinase Inhibitor ◽  
Platelet Activating Factor ◽  
Rho Kinase ◽  
Thromboxane Receptor ◽  
Pressor Responses ◽  
Kinase Pathway

Platelet-activating factor (PAF) contracts smooth muscle of airways and vessels primarily via release of thromboxane. Contraction of smooth muscle is thought to be mediated either by calcium and inositol trisphosphate (IP3)-dependent activation of the myosin light chain kinase or, alternatively, via the recently discovered Rho-kinase pathway. Here we investigated the contribution of these two pathways to PAF and thromboxane receptor-mediated broncho- and vasoconstriction in two different rat models: the isolated perfused lung (IPL) and precision-cut lung slices. Inhibition of the IP3 receptor (1–10 μM xestospongin C) or inhibition of phosphatidylinositol-specific PLC (30 μM L-108) did not affect bronchoconstriction but attenuated the sustained vasoconstriction by PAF. Inhibition of myosin light chain kinase (35 μM ML-7) or of calmodulin kinase kinase (26 μM STO609), which regulates the phosphorylation of the myosin light chain, had only a small effect on PAF- or thromboxane-induced pressor responses. Similarly, calmidazolium (10 μM), which inhibits calmodulin-dependent proteins, only weakly reduced the airway responses. In contrast, Y-27632 (10 μM), a Rho-kinase inhibitor, attenuated the thromboxane release triggered by PAF and provided partial or complete inhibition against PAF- and thromboxane-induced pressor responses, respectively. Together, our data indicate that PAF- and thus thromboxane receptor-mediated smooth muscle contraction depends largely on the Rho-kinase pathway.

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 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.

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