Potential Shifts and Intracellular Signaling in Smooth Muscle and Exocrine Cells: Role of the Secretory Potential (a Working Hypothesis)

2003 ◽  
Vol 35 (3/4) ◽  
pp. 330 ◽  
Author(s):  
V. V. Man'ko ◽  
M. Yu. Klevets
Keyword(s):  
Smooth Muscle ◽  
Intracellular Signaling ◽  
Exocrine Cells ◽  
Working Hypothesis ◽  
Secretory Potential ◽  
Potential Shifts

scholarly journals Aortic dissection is associated with reduced polycystin-1 expression, an abnormality that leads to increased ERK phosphorylation in vascular smooth muscle cells

2016 ◽  
Author(s):  
J. Feng ◽  
S. Ge ◽  
L. Zhang ◽  
H. Che ◽  
C. Liang
Keyword(s):  
Smooth Muscle ◽  
Aortic Dissection ◽  
Vascular Smooth Muscle ◽  
Signaling Pathway ◽  
Intracellular Signaling ◽  
High Morbidity ◽  
Biological Processes ◽  
Phenotypic Switch ◽  
Erk Phosphorylation

The vascular smooth muscle cell (VSMC) phenotypic switch is a key pathophysiological change in various cardiovascular diseases, such as aortic dissection (AD), with a high morbidity. Polycystin-1 (PC1) is significantly downregulated in the VSMCs of AD patients. PC1 is an integral membrane glycoprotein and kinase that regulates different biological processes, including cell proliferation, apoptosis, and cell polarity. However, the role of PC1 in intracellular signaling pathways remains poorly understood. In this study, PC1 downregulation in VSMCs promoted the expression of SM22α, ACTA2 and calponin 1 (CNN1) proteins. Furthermore, PC1 downregulation in VSMCs upregulated phospho-MEK, phospho-ERK and myc, but did not change phospho-JNK and phospho-p38. These findings suggest that the MEK/ERK/myc signaling pathway is involved in PC1-mediated human VSMC phenotypic switch. Opposite results were observed when an ERK inhibitor was used in VSMCs downregulated by PC1. When the C-terminal domain of PC1 (PC1 C-tail) was overexpressed in VSMCs, the expression levels of phosphor-ERK, myc, SM22α, ACTA2 and CNN1 proteins were downregulated. The group with the overexpressed mutant protein (S4166A) in the PC1 C-tail showed similar results to the group with the downregulated PC1 in VSMCs. These results suggest that the Ser at the 4166 site in PC1 is crucial in the PC1 mediated MEK/ERK/myc signaling pathway, which might be the key pathophysiological cause of AD.

Role of myosin light chain kinase in cardiotrophin-1-induced cardiac myofibroblast cell migration

2011 ◽  
Vol 301 (2) ◽  
pp. H514-H522 ◽  
Author(s):  
Darren H. Freed ◽  
Lisa Chilton ◽  
Yun Li ◽  
Aran L. Dangerfield ◽  
Joshua E. Raizman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Membrane Potential ◽  
Light Chain ◽  
Intracellular Signaling ◽  
Myosin Light Chain Kinase ◽  
Myosin Light Chain ◽  
Tissue Injury ◽  
Smooth Muscle Actin

Chemotactic movement of myofibroblasts is recognized as a common means for their sequestration to the site of tissue injury. Following myocardial infarction (MI), recruitment of cardiac myofibroblasts to the infarct scar is a critical step in wound healing. Contractile myofibroblasts express embryonic smooth muscle myosin, α-smooth muscle actin, as well as collagens I and III. We examined the effects of cardiotrophin-1 (CT-1) in the induction of primary rat ventricular myofibroblast motility. Changes in membrane potential (Em) and Ca2+entry were studied to reveal the mechanisms for induction of myofibroblast migration. CT-1-induced cardiac myofibroblast cell migration, which was attenuated through the inhibition of JAK2 (25 μM AG490), and myosin light chain kinase (20 μM ML-7). Inhibition of K+channels (1 mM tetraethylammonium or 100 μM 4-aminopyridine) and nonselective cation channels by 10 μM gadolinium (Gd3+) significantly reduced migration in the presence of CT-1. CT-1 treatment caused a significant increase in myosin light chain phosphorylation, which could be inhibited by incubation in Ca2+-free conditions or by application of AG490, ML-7, and W7 (100 μM; calmodulin inhibitor). Monitoring myofibroblast membrane potential with potentiometric fluorescent DiBAC4( 3 ) dye revealed a biphasic response to CT-1 consisting of an initial depolarization followed by hyperpolarization. Increased intracellular Ca2+, as assessed by fluo 3, occurred immediately after membrane depolarization and attenuated at the time of maximal hyperpolarization. CT-1 exerts chemotactic effects via multiple parallel signaling modalities in ventricular myofibroblasts, including changes in membrane potential, alterations in intracellular calcium, and activation of a number of intracellular signaling pathways. Further study is warranted to determine the precise role of K+currents in this process.

scholarly journals Cyclic AMP-Rap1A signaling activates RhoA to induce α2c-adrenoceptor translocation to the cell surface of microvascular smooth muscle cells

2012 ◽  
Vol 303 (5) ◽  
pp. C499-C511 ◽  
Author(s):  
Selvi C. Jeyaraj ◽  
Nicholas T. Unger ◽  
Ali H. Eid ◽  
Srabani Mitra ◽  
N. Paul El-Dahdah ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cyclic Amp ◽  
Cell Surface ◽  
Smooth Muscle Cells ◽  
Intracellular Signaling ◽  
Muscle Cells ◽  
Small Gtpase ◽  
Hek293 Cells ◽  
Intracellular Camp

Intracellular signaling by the second messenger cyclic AMP (cAMP) activates the Ras-related small GTPase Rap1 through the guanine exchange factor Epac. This activation leads to effector protein interactions, activation, and biological responses in the vasculature, including vasorelaxation. In vascular smooth muscle cells derived from human dermal arterioles (microVSM), Rap1 selectively regulates expression of G protein-coupled α2C-adrenoceptors (α2C-ARs) through JNK-c-jun nuclear signaling. The α2C-ARs are generally retained in the trans-Golgi compartment and mobilize to the cell surface and elicit vasoconstriction in response to cellular stress. The present study used human microVSM to examine the role of Rap1 in receptor localization. Complementary approaches included murine microVSM derived from tail arteries of C57BL6 mice that express functional α2C-ARs and mice deficient in Rap1A (Rap1A-null). In human microVSM, increasing intracellular cAMP by direct activation of adenylyl cyclase by forskolin (10 μM) or selectively activating Epac-Rap signaling by the cAMP analog 8-pCPT-2′- O-Me-cAMP (100 μM) activated RhoA, increased α2C-AR expression, and reorganized the actin cytoskeleton, increasing F-actin. The α2C-ARs mobilized from the perinuclear region to intracellular filamentous structures and to the plasma membrane. Similar results were obtained in murine wild-type microVSM, coupling Rap1-Rho-actin dynamics to receptor relocalization. This signaling was impaired in Rap1A-null murine microVSM and was rescued by delivery of constitutively active (CA) mutant of Rap1A. When tested in heterologous HEK293 cells, Rap1A-CA or Rho-kinase (ROCK-CA) caused translocation of functional α2C-ARs to the cell surface (∼4- to 6-fold increase, respectively). Together, these studies support vascular bed-specific physiological role of Rap1 and suggest a role in vasoconstriction in microVSM.

The role of Na+/Ca2+ exchanger in opossum esophageal smooth muscle contractillty

2001 ◽  
Vol 120 (5) ◽  
pp. A57-A57 ◽  
Author(s):  
P ROY ◽  
Y ZHANG ◽  
S LORENSSEN ◽  
M BLENNERHASETT ◽  
W PATERSON
Keyword(s):  
Smooth Muscle

Role of stat6 in hypercontractility of murine small intestinal smooth muscle induced by nematode infection

2001 ◽  
Vol 120 (5) ◽  
pp. A534-A534
Author(s):  
A ZHAO ◽  
D MULLOY ◽  
J URBANJR ◽  
W GAUSE ◽  
T SHEADONOHUE
Keyword(s):  
Smooth Muscle ◽  
Nematode Infection ◽  
Intestinal Smooth Muscle ◽  
Small Intestinal

The role of WNT/b-catenin signaling in smooth muscle cells during lung development and repair

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
A Moiseenko ◽  
E El Agha ◽  
B MacKenzie ◽  
S De Langhe ◽  
S Bellusci
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Lung Development ◽  
Muscle Cells

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

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