V. Aging and gastrointestinal smooth muscle: from signal transduction to contractile proteins

2003 ◽  
Vol 284 (1) ◽  
pp. G1-G7 ◽  
Author(s):  
Khalil N. Bitar
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Length Distribution ◽  
Muscle Cells ◽  
Contractile Proteins ◽  
Signal Transduction Pathways ◽  
Adult Rats ◽  
Hsp27 Phosphorylation ◽  
Old Rats

The object of this theme is to offer new perspectives on the effect of aging on signal-transduction pathways associated with agonist-induced contraction of smooth muscle cells from the colon. Smooth muscle cells from old rats (32 mo old) exhibit limited cell length distribution and diminished contractility. The observed reduced contractile response may be due to the effect of aging on signal-transduction pathways, especially an inhibition of the tyrosine kinase-Src kinase pathway, a reduced activation of the PKC pathway, and a reduced association of contractile proteins [heat shock protein 27 (HSP27)-tropomyosin, HSP27-actin, actin-myosin]. Levels of HSP27 phosphorylation are also reduced compared with adult rats.

Signal Transduction Pathways in Smooth Muscle Cells

2004 ◽  
pp. 213-231 ◽  
Author(s):  
Sabina Vogel ◽  
Thomas Kubin ◽  
Miroslav Barancik ◽  
Elisabeth Deindl ◽  
Dietmar von der Ahe ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Signal Transduction Pathways

scholarly journals Sphingosine-1-phosphate inhibits PDGF-induced chemotaxis of human arterial smooth muscle cells: spatial and temporal modulation of PDGF chemotactic signal transduction.

1995 ◽  
Vol 130 (1) ◽  
pp. 193-206 ◽  
Author(s):  
K E Bornfeldt ◽  
L M Graves ◽  
E W Raines ◽  
Y Igarashi ◽  
G Wayman ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Actin Filament ◽  
Muscle Cells ◽  
Calcium Mobilization ◽  
Signal Transduction Pathways ◽  
Pdgf Receptor ◽  
Sphingosine 1 Phosphate ◽  
Arterial Smooth Muscle Cells

Activation of the PDGF receptor on human arterial smooth muscle cells (SMC) induces migration and proliferation via separable signal transduction pathways. Sphingosine-1-phosphate (Sph-1-P) can be formed following PDGF receptor activation and therefore may be implicated in PDGF-receptor signal transduction. Here we show that Sph-1-P does not significantly affect PDGF-induced DNA synthesis, proliferation, or activation of mitogenic signal transduction pathways, such as the mitogen-activated protein (MAP) kinase cascade and PI 3-kinase, in human arterial SMC. On the other hand, Sph-1-P strongly mimics PDGF receptor-induced chemotactic signal transduction favoring actin filament disassembly. Although Sph-1-P mimics PDGF, exogenously added Sph-1-P induces more prolonged and quantitatively greater PIP2 hydrolysis compared to PDGF-BB, a markedly stronger calcium mobilization and a subsequent increase in cyclic AMP levels and activation of cAMP-dependent protein kinase. This excessive and prolonged signaling favors actin filament disassembly by Sph-1-P, and results in inhibition of actin nucleation, actin filament assembly and formation of focal adhesion sites. Sph-1-P-induced interference with the dynamics of PDGF-stimulated actin filament disassembly and assembly results in a marked inhibition of cell spreading, of extension of the leading lamellae toward PDGF, and of chemotaxis toward PDGF. The results suggest that spatial and temporal changes in phosphatidylinositol turnover, calcium mobilization and actin filament disassembly may be critical to PDGF-induced chemotaxis and suggest a possible role for endogenous Sph-1-P in the regulation of PDGF receptor chemotactic signal transduction.

Heterogeneity of Receptors and Signal Transduction Pathways in Smooth Muscle Cells of the Gut

1990 ◽  
pp. 73-79
Author(s):  
Gabriel M. Makhlouf ◽  
John R. Grider ◽  
Giufeppina Morini ◽  
Lee McHenry ◽  
Daniel C. Martin ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Signal Transduction Pathways

Ca2+ signaling in mouse mesenteric small arteries: myogenic tone and adrenergic vasoconstriction

2007 ◽  
Vol 292 (3) ◽  
pp. H1523-H1532 ◽  
Author(s):  
Joseph Zacharia ◽  
Jin Zhang ◽  
W. Gil Wier
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Molecular Basis ◽  
Physiological State ◽  
Muscle Cells ◽  
Intraluminal Pressure ◽  
Myogenic Tone ◽  
Signal Transduction Pathways ◽  
Small Arteries

Arteries that have developed myogenic tone (MT) are in a markedly different physiological state compared with those that have not, with higher cytosolic [Ca2+] and altered activity of several signal transduction pathways. In this study, we sought to determine whether α1-adrenoceptor-induced Ca2+ signaling is different in pressurized arteries that have spontaneously developed MT (the presumptive physiological state) compared with those that have not (a common experimental state). At 32°C and intraluminal pressure of 70 mmHg, cytoplasmic [Ca2+] was steady in most smooth muscle cells (SMCs). In a minority of cells (34%), however, at least one propagating Ca2+ wave occurred. α1-Adrenoceptor activation (phenylephrine, PE; 0.1–10.0 μM) caused strong vasoconstriction and markedly increased the frequency of Ca2+ waves (in virtually all cells). However, when cytosolic [Ca2+] was elevated experimentally in these arteries ([K+] 20 mM), PE failed to elicit Ca2+ waves, although it did elevate [Ca2+] (F/F0) further and caused further vasoconstriction. During development of MT, the cytosolic [Ca2+] (F/F0) in individual SMCs increased, Ca2+ waves disappeared (from SMCs that had them), and small Ca2+ ripples (frequency ∼0.05 Hz) appeared in ∼13% of cells. PE elicited only spatially uniform increases in [Ca2+] and a smaller change in diameter (than in the absence of MT). Nevertheless, when cytosolic [Ca2+] and MT were decreased by nifedipine (1 μM), PE did elicit Ca2+ waves. Thus α1-adrenoceptor-mediated Ca2+ signaling is markedly different in arteries with and without MT, perhaps due to the elevated [Ca2+], and may have a different molecular basis. α1-Adrenoceptor-induced vasoconstriction may be supported either by Ca2+ waves or by steady elevation of cytoplasmic [Ca2+], depending on the amount of MT.

scholarly journals Aging-associated oxidative stress leads to decrease in IAS tone via RhoA/ROCK downregulation

2014 ◽  
Vol 306 (11) ◽  
pp. G983-G991 ◽  
Author(s):  
Jagmohan Singh ◽  
Sumit Kumar ◽  
Chadalavada Vijay Krishna ◽  
Satish Rattan
Keyword(s):  
Oxidative Stress ◽  
Signal Transduction ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
The Elderly ◽  
Rock Inhibitor ◽  
Before And After ◽  
Old Rats ◽  
Underlying Mechanisms

Internal anal sphincter (IAS) tone plays an important role in rectoanal incontinence (RI). IAS tone may be compromised during aging, leading to RI in certain patients. We examined the influence of oxidative stress in the aging-associated decrease in IAS tone (AADI). Using adult (4–6 mo old) and aging (24–30 mo old) rats, we determined the effect of oxidative stress on IAS tone and the regulatory RhoA/ROCK signal transduction cascade. We determined the effect of the oxidative stress inducer LY83583, which produces superoxide anions (O2·−), on basal and stimulated IAS tone before and after treatment of intact smooth muscle strips and smooth muscle cells with the O2·− scavenger SOD. Our data showed that AADI was associated with a decrease in RhoA/ROCK expression at the transcriptional and translational levels. Oxidative stress with a LY83583-mediated decrease in IAS tone and relaxation of IAS smooth muscle cells was associated with a decrease in RhoA/ROCK signal transduction, which was reversible by SOD. In addition, LY83583 caused a significant decrease in IAS contraction produced by the RhoA activator and a known RhoA/ROCK agonist, U46619 , that was also reversible by SOD. The inhibitory effects of LY83583 and the ROCK inhibitor Y27632 on the U46619-induced increase in IAS tone were similar. We conclude that an increase in oxidative stress plays an important role in AADI in the elderly and may be one of the underlying mechanisms of RI in certain aging patients.

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