ICI 182,780 Attenuates Selective Upregulation of Uterine Artery Cystathionine β-Synthase Expression in Rat Pregnancy.
ICI 182,780 Attenuates Selective Upregulation of Uterine Artery Cystathionine β-Synthase Expression in Rat Pregnancy.
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DOI：
10.3390/ijms241814384
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发表时间：
2023-09-21
影响因子：
5.6
通讯作者：
Chen DB
中科院分区：
文献类型：
--
作者：
Bai J;Li Y;Yan G;Zhou J;Salmeron AG;Fategbe OT;Kumar S;Chen X;Chen DB
由胱硫醚β-合酶（CBS）和胱硫醚-γ裂解酶（CSE）产生的内源性硫化氢（H2S）已成为一种新的子宫血管扩张剂，有助于妊娠相关的子宫血流量增加，从而保护妊娠健康。通过外源性雌激素替代刺激子宫动脉（UA）H2S产生，并通过选择性上调CBS而不改变CSE，与妊娠期间内源性雌激素升高相关。然而，内源性雌激素如何调节妊娠期子宫动脉CBS表达尚不清楚。本研究旨在验证内源性雌激素通过特异性雌激素受体（ER）选择性刺激UA CBS表达的假设。在NP和P（妊娠第20天，GD 20）大鼠新鲜UA环的器官培养物中，E2β（0.01至100 nM）处理刺激CBS而非CSE mRNA，P与NP UA相比，对所有剂量的E2β均有更大的反应。ER拮抗剂ICI 182，780（ICI，1 µM）完全减弱了NP和P大鼠UA中E2β刺激的CBS mRNA。皮下注射ICI 182，780（0.3 mg/rat）24 h后，GD 19 P大鼠的UA CBS表达明显受到抑制，但mRNA表达无明显变化，这与内皮细胞和平滑肌细胞CBS（但不包括CSE）蛋白的降低一致。ICI不改变肠系膜动脉和肾动脉CBS和CSE mRNA。此外，ICI降低UA中的内皮型一氧化氮合酶mRNA，但在肠系膜或肾动脉中不降低。因此，妊娠增强UA CBS/H2S生产是通过内源性雌激素的作用介导的，通过特定的ER在妊娠大鼠。
Endogenous hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine-γ lyase (CSE) has emerged as a novel uterine vasodilator contributing to pregnancy-associated increases in uterine blood flow, which safeguard pregnancy health. Uterine artery (UA) H2S production is stimulated via exogenous estrogen replacement and is associated with elevated endogenous estrogens during pregnancy through the selective upregulation of CBS without altering CSE. However, how endogenous estrogens regulate uterine artery CBS expression in pregnancy is unknown. This study was conducted to test a hypothesis that endogenous estrogens selectively stimulate UA CBS expression via specific estrogen receptors (ER). Treatment with E2β (0.01 to 100 nM) stimulated CBS but not CSE mRNA in organ cultures of fresh UA rings from both NP and P (gestational day 20, GD20) rats, with greater responses to all doses of E2β tested in P vs. NP UA. ER antagonist ICI 182,780 (ICI, 1 µM) completely attenuated E2β-stimulated CBS mRNA in both NP and P rat UA. Subcutaneous injection with ICI 182,780 (0.3 mg/rat) of GD19 P rats for 24 h significantly inhibited UA CBS but not mRNA expression, consistent with reduced endothelial and smooth muscle cell CBS (but not CSE) protein. ICI did not alter mesenteric and renal artery CBS and CSE mRNA. In addition, ICI decreased endothelial nitric oxide synthase mRNA in UA but not in mesenteric or renal arteries. Thus, pregnancy-augmented UA CBS/H2S production is mediated by the actions of endogenous estrogens via specific ER in pregnant rats.
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影响因子：
9.8
作者：
Jung E;Romero R;Yeo L;Gomez-Lopez N;Chaemsaithong P;Jaovisidha A;Gotsch F;Erez O
通讯作者：
Erez O
影响因子：
3.5
作者：
Bai, Jin;Lechuga, Thomas J.;Chen, Dong-bao
通讯作者：
Chen, Dong-bao
影响因子：
7.2
作者：
Bernstein, IM;Ziegler, WF;Badger, GJ
通讯作者：
Badger, GJ
DOI：
10.1016/0002-9378(73)90552-8
发表时间：
1973-01-01
影响因子：
9.8
作者：
KILLAM, AP;BATTAGLIA, FC;ROSENFELD, CR
通讯作者：
ROSENFELD, CR
影响因子：
4.8
作者：
Lechuga, Thomas J.;Zhang, Hong-hai;Chen, Dong-bao
通讯作者：
Chen, Dong-bao