Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation

Lili Sheibani, Thomas J. Lechuga, Honghai Zhang, Afshan Hameed, Deborah A. Wing, Sathish Kumar, Charles R. Rosenfeld, Dong Bao Chen

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-betasynthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P>NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P>NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.

Original languageEnglish (US)
Article numberbio143834
Pages (from-to)664-672
Number of pages9
JournalBiology of Reproduction
Volume96
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Cystathionine
Cystathionine beta-Synthase
Cystathionine gamma-Lyase
Uterine Artery
Vasodilation
Up-Regulation
Pregnancy
Endothelium
Smooth Muscle
Proteins
Myography
Hydrogen Sulfide
Messenger RNA
Mesentery
Follicular Phase
Angiogenesis Inducing Agents
Luteal Phase
Methylene Blue
Menstrual Cycle
Vasodilator Agents

Keywords

  • Cystathionine-beta-synthase
  • Hydrogen sulfide
  • Pregnancy
  • Uterine vasodilation
  • Women

ASJC Scopus subject areas

  • Cell Biology

Cite this

Sheibani, L., Lechuga, T. J., Zhang, H., Hameed, A., Wing, D. A., Kumar, S., ... Chen, D. B. (2017). Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation. Biology of Reproduction, 96(3), 664-672. [bio143834]. https://doi.org/10.1095/biolreprod.116.143834

Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation. / Sheibani, Lili; Lechuga, Thomas J.; Zhang, Honghai; Hameed, Afshan; Wing, Deborah A.; Kumar, Sathish; Rosenfeld, Charles R.; Chen, Dong Bao.

In: Biology of Reproduction, Vol. 96, No. 3, bio143834, 01.03.2017, p. 664-672.

Research output: Contribution to journalArticle

Sheibani, Lili ; Lechuga, Thomas J. ; Zhang, Honghai ; Hameed, Afshan ; Wing, Deborah A. ; Kumar, Sathish ; Rosenfeld, Charles R. ; Chen, Dong Bao. / Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation. In: Biology of Reproduction. 2017 ; Vol. 96, No. 3. pp. 664-672.
@article{e91947d1e16e4fbfa8c6f69905682ad2,
title = "Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation",
abstract = "Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-betasynthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P>NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P>NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.",
keywords = "Cystathionine-beta-synthase, Hydrogen sulfide, Pregnancy, Uterine vasodilation, Women",
author = "Lili Sheibani and Lechuga, {Thomas J.} and Honghai Zhang and Afshan Hameed and Wing, {Deborah A.} and Sathish Kumar and Rosenfeld, {Charles R.} and Chen, {Dong Bao}",
year = "2017",
month = "3",
day = "1",
doi = "10.1095/biolreprod.116.143834",
language = "English (US)",
volume = "96",
pages = "664--672",
journal = "Biology of Reproduction",
issn = "0006-3363",
publisher = "Society for the Study of Reproduction",
number = "3",

}

TY - JOUR

T1 - Augmented H2S production via cystathionine-beta-synthase upregulation plays a role in pregnancy-associated uterine vasodilation

AU - Sheibani, Lili

AU - Lechuga, Thomas J.

AU - Zhang, Honghai

AU - Hameed, Afshan

AU - Wing, Deborah A.

AU - Kumar, Sathish

AU - Rosenfeld, Charles R.

AU - Chen, Dong Bao

PY - 2017/3/1

Y1 - 2017/3/1

N2 - Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-betasynthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P>NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P>NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.

AB - Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-betasynthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P>NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P>NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.

KW - Cystathionine-beta-synthase

KW - Hydrogen sulfide

KW - Pregnancy

KW - Uterine vasodilation

KW - Women

UR - http://www.scopus.com/inward/record.url?scp=85022339166&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85022339166&partnerID=8YFLogxK

U2 - 10.1095/biolreprod.116.143834

DO - 10.1095/biolreprod.116.143834

M3 - Article

C2 - 28339573

AN - SCOPUS:85022339166

VL - 96

SP - 664

EP - 672

JO - Biology of Reproduction

JF - Biology of Reproduction

SN - 0006-3363

IS - 3

M1 - bio143834

ER -