Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility

Butler, Trent; Paul, Jay P.; Europe-Finner, Nick; Smith, Roger; Chan, Eng‐Cheng

doi:10.1152/ajpcell.00161.2012

Cited by 44 publications

(58 citation statements)

References 279 publications

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“…5f–i ). Ceramide-activated serine-threonine phosphatases (CAPPs) such as phosphatase 1 (PP1) and phosphatase 2A (PP2A), which have a defined role in smooth muscle cell contractility 39 , have been found to interact with ceramide 40 . Increased levels of cer-C18, cer-C20 and cer-C22 in smooth muscle cells of SMC-Nogo-A/B-deficient mice may therefore be responsible for the reduced myogenic tone observed in these mice.…”

Section: Resultsmentioning

confidence: 99%

Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure

Cantalupo

Zhang

Kothiya

et al. 2015

Nat Med

106

181

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Endothelial dysfunction is a critical factor in many cardiovascular diseases, including hypertension. Although lipid signaling has been implicated in endothelial dysfunction and cardiovascular disease, specific molecular mechanisms are poorly understood. Here we report that Nogo-B, a membrane protein of the endoplasmic reticulum, regulates endothelial sphingolipid biosynthesis with direct effects on vascular function and blood pressure. Nogo-B inhibits serine palmitoyltransferase, the rate-limiting enzyme of the de novo sphingolipid biosynthetic pathway, thereby controlling production of endothelial sphingosine 1-phosphate and autocrine, G protein–coupled receptor–dependent signaling by this metabolite. Mice lacking Nogo-B either systemically or specifically in endothelial cells are hypotensive, resistant to angiotensin II–induced hypertension and have preserved endothelial function and nitric oxide release. In mice that lack Nogo-B, pharmacological inhibition of serine palmitoyltransferase with myriocin reinstates endothelial dysfunction and angiotensin II–induced hypertension. Our study identifies Nogo-B as a key inhibitor of local sphingolipid synthesis and shows that autocrine sphingolipid signaling within the endothelium is critical for vascular function and blood pressure homeostasis.

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Section: Resultsmentioning

confidence: 99%

Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure

Cantalupo

Zhang

Kothiya

et al. 2015

Nat Med

106

181

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“…Pormation of the Ca+^-CalM complex results in the activation of a key enzyme, myosin light chain kinase (MLCK) and causes an immediate and marked increase in the phosphorylation of myosin regulatory light chain-20 (MLC20) and subsequent cross-bridge cycling (25). Phosphorylation of MLC20 by MLCK is the principal determinant of the amplitude and duration of contraction (26). MLCK contains several phosphorylation target sites for protein kinase A, protein kinase C (PKC) and other kinases (2).…”

Section: Contractionmentioning

confidence: 99%

A close look at the contraction and relaxation of the myometrium; the role of calcium

Pehlivanoğlu¹,

Bayrak²,

Doğan³

2013

J Turkish German Gynecol Assoc

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The function and regulation of the myometrium, especially during pregnancy, labour and birth are important in reproductive physiology. It is crucial to understand the mechanisms that generate and modulate uterine contractility in order to be able to prevent and/or treat the problems related with the myometrium. A limited understanding of the cellular and molecular events underlying these phenomena complicates the situation. Various agonists, hormones, transmitters and/or chemicals are related to the regulation of the functions of the myometrium. Although notable advances regarding the key steps in receptor signalling explaining the actions of these factors have been achieved, a good deal of information is still necessary to understand this vital process. A better comprehension of myometrium physiology and the translation of research findings to clinical settings will help progress in women's health. In this review, we attempt to present a critical overview of myometrial functions and focus specifically on the role of calcium.

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“…Formation of the Ca 2+ -CalM complex activates the enzyme myosin light chain kinase (MLCK) resulting in an increase in the phosphorylation of myosin regulatory light chain-20 (MLC20) and subsequent cross-bridge cycling (Shojo & Kaneko 2001). MLC20 phosphorylation by MLCK is the principal determinant of the amplitude and duration of contraction (Butler et al 2013;McConnell & Wadzinski 2009). MLCK contains several phosphorylation target sites for protein kinase A, protein kinase C (PKC) and other kinases (Aguilar & Mitchell 2010;Wray et al 2001) which may contribute to its activity.…”

Section: Discussionmentioning

confidence: 99%

<i>Dryopteris filix-mas</i> (Dryopteridaceae) leaves inhibit mouse uterine activity

Bafor

Omokaro

Uwumarongie³

et al. 2017

JOMPED

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Background: The plant Dryopteris filix-mas has been used traditionally for its uterine-stimulant effects.Aim: The current study is therefore aimed at investigating and determining the effect of the leaves of D. filix-mas on uterine contractility in vitro.Setting: Fresh leaves of D. filix-mas were collected from a river bank in the south-western part of Nigeria.Methods: The leaves of D. filix-mas were cleaned, dried and extracted in methanol. The extract (0.07 µg/mL–21.0 µg/mL) was tested on the isolated mouse uteri in order to determine activity on spontaneous-induced uterine contractions. Subsequently the extract (0.005 mg/mL and 0.05 mg/mL) was tested on oxytocin-induced contraction (0.00017 ng/mL–4.98 ng/mL) in calcium-containing media, submaximal oxytocin-induced contraction (0.116 ng/mL) in calcium-free media and in the presence of high KCl-induced uterine contractions (80 mM). The extract was also subjected to mass spectrometric determination of secondary metabolites.Results: The plant extract inhibited spontaneous-induced contractions with IC50 amplitude = 658.41 ng/mL ± 0.11 ng/mL and IC50 frequency = 175.32 ng/mL ± 0.53 ng/mL. The plant extract inhibited oxytocin-induced and high KCl-induced uterine contractions (p < 0.01 at 0.5 mg/mL). The plant extract had no effect on oxytocin-induced contractions under calcium-free conditions. Secondary metabolites belonging to classes of fatty acids, alkaloids, saponin glycosides, amino acids, limonoids, terpenes and porphyrins were identified.Conclusion: The current study reports an inhibitory effect of the plant on uterine contractility in this study, suggesting possible application as a tocolytic or as a contraceptive, as most contraceptive plants have shown uterine-relaxing effect.

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Role of serine-threonine phosphoprotein phosphatases in smooth muscle contractility

Cited by 44 publications

References 279 publications

Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure

Nogo-B regulates endothelial sphingolipid homeostasis to control vascular function and blood pressure

A close look at the contraction and relaxation of the myometrium; the role of calcium

<i>Dryopteris filix-mas</i> (Dryopteridaceae) leaves inhibit mouse uterine activity

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