Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.

<h4>Background</h4>Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2)S) has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2)S produced locally in the control...

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Autores principales: Xing-Ji You, Chen Xu, Jian-Qiang Lu, Xiao-Yan Zhu, Lu Gao, Xiao-Rui Cui, Yuan Li, Hang Gu, Xin Ni
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Publicado: Public Library of Science (PLoS) 2011
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spelling oai:doaj.org-article:af4f7fa5596a44639395b9808d2decbc2021-11-18T06:47:28ZExpression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.1932-620310.1371/journal.pone.0023788https://doaj.org/article/af4f7fa5596a44639395b9808d2decbc2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21886822/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2)S) has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2)S produced locally in the control of uterine contractility during labour is unknown.<h4>Methodology/principal findings</h4>Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS), the principle enzymes responsible for H(2)S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H(2)S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10(-7)-10(-2) mol/L), a precursor of H(2)S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10(-3) mol/L) increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips.<h4>Conclusion/significance</h4>H(2)S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H(2)S synthetic enzymes is down-regulated during labour, suggesting that H(2)S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.Xing-Ji YouChen XuJian-Qiang LuXiao-Yan ZhuLu GaoXiao-Rui CuiYuan LiHang GuXin NiPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 8, p e23788 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Xing-Ji You
Chen Xu
Jian-Qiang Lu
Xiao-Yan Zhu
Lu Gao
Xiao-Rui Cui
Yuan Li
Hang Gu
Xin Ni
Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
description <h4>Background</h4>Human uterus undergoes distinct molecular and functional changes during pregnancy and parturition. Hydrogen sulfide (H(2)S) has recently been shown to play a key role in the control of smooth muscle tension. The role of endogenous H(2)S produced locally in the control of uterine contractility during labour is unknown.<h4>Methodology/principal findings</h4>Human myometrium biopsies were obtained from pregnant women undergoing cesarean section at term. Immunohistochemistry analysis showed that cystathionine-γ-lyase (CSE) and cystathionine-β-synthetase (CBS), the principle enzymes responsible for H(2)S generation, were mainly localized to smooth muscle cells of human pregnant myometrium. The mRNA and protein expression of CBS as well as H(2)S production rate were down-regulated in labouring tissues compared to nonlabouring tissues. Cumulative administration of L-cysteine (10(-7)-10(-2) mol/L), a precursor of H(2)S, caused a dose-dependent decrease in the amplitude of spontaneous contractions in nonlabouring and labouring myometrium strips. L-cysteine at high concentration (10(-3) mol/L) increased the frequency of spontaneous contractions and induced tonic contraction. These effects of L-cysteine were blocked by the inhibitors of CBS and CSE. Pre-treatment of myometrium strips with glibenclamide, an inhibitor of ATP-sensitive potassium (K(ATP)) channels, abolished the inhibitory effect of L-cysteine on spontaneous contraction amplitude. The effects of L-cysteine on the amplitude of spontaneous contractions and baseline muscle tone were less potent in labouring tissues than that in nonlabouring strips.<h4>Conclusion/significance</h4>H(2)S generated by CSE and CBS locally exerts dual effects on the contractility of pregnant myometrium. Expression of H(2)S synthetic enzymes is down-regulated during labour, suggesting that H(2)S is one of the factors involved in the transition of pregnant uterus from quiescence to contractile state after onset of parturition.
format article
author Xing-Ji You
Chen Xu
Jian-Qiang Lu
Xiao-Yan Zhu
Lu Gao
Xiao-Rui Cui
Yuan Li
Hang Gu
Xin Ni
author_facet Xing-Ji You
Chen Xu
Jian-Qiang Lu
Xiao-Yan Zhu
Lu Gao
Xiao-Rui Cui
Yuan Li
Hang Gu
Xin Ni
author_sort Xing-Ji You
title Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
title_short Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
title_full Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
title_fullStr Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
title_full_unstemmed Expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
title_sort expression of cystathionine β-synthase and cystathionine γ-lyase in human pregnant myometrium and their roles in the control of uterine contractility.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/af4f7fa5596a44639395b9808d2decbc
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