Cystathionine γ-lyase promotes estrogen-stimulated uterine artery blood flow via glutathione homeostasis.
Cystathionine γ-lyase promotes estrogen-stimulated uterine artery blood flow via glutathione homeostasis.
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DOI：
10.1016/j.redox.2020.101827
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发表时间：
2021-04
期刊：
影响因子：
11.4
通讯作者：
Hurt KJ
中科院分区：
文献类型：
--
作者：
Bok R;Guerra DD;Lorca RA;Wennersten SA;Harris PS;Rauniyar AK;Stabler SP;MacLean KN;Roede JR;Brown LD;Hurt KJ
在妊娠期间，雌激素（E2）通过增强一氧化氮（NO）依赖性血管舒张来刺激子宫动脉血流（UBF）。胱硫醚γ-裂解酶（CSE）通过产生硫化氢（H2S）和通过L-半胱氨酸产生维持还原型与氧化型细胞内谷胱甘肽（GSH/GSSG）的比率来促进血管NO信号传导。由于氧化还原稳态可以影响NO信号，我们假设CSE通过调节局部细胞内半胱氨酸代谢和GSH/GSSG水平来介导E2刺激UBF，以促进氧化还原稳态。使用非妊娠的卵巢切除WT和CSE无效（CSE KO）小鼠，我们对小鼠子宫和肾动脉进行微超声以评估外源性E2刺激后血流的变化。我们定量血清和子宫动脉NO代谢产物（NOx），血清氨基酸，子宫和肾动脉GSH/GSSG。WT和CSE KO小鼠表现出相似的基线子宫和肾血流。与WT不同，CSE KO小鼠未表现出预期的E2刺激UBF。两种基因型的肾血流均对E2不敏感。虽然基线时不同基因型之间的血清和子宫动脉NOx相似，但E2可降低CSE KO血清中的NOx。CSE KO血清中的半胱氨酸也较低，而瓜氨酸和同型半胱氨酸水平升高。E_2和CSE缺失使子宫动脉GSH/GSSG相加性降低。相反，肾动脉GSH/GSSG对E2或CSE缺失不敏感。总之，这些研究结果表明，CSE维持子宫动脉GSH/GSSG促进子宫动脉中的氮能信号传导，并且是UBF正常E2刺激所需的。这些数据对妊娠病理生理学和特定血管床的选择性激素反应有影响。CSE基因敲除小鼠表现出子宫动脉血流的异常雌激素增加。雌激素降低CSE无效小鼠子宫动脉一氧化氮代谢产物。CSE丢失和雌激素增加性损害子宫动脉谷胱甘肽稳态。CSE损失和雌激素都不会影响肾动脉血流量或谷胱甘肽。
During pregnancy, estrogen (E2) stimulates uterine artery blood flow (UBF) by enhancing nitric oxide (NO)-dependent vasodilation. Cystathionine γ-lyase (CSE) promotes vascular NO signaling by producing hydrogen sulfide (H2S) and by maintaining the ratio of reduced-to-oxidized intracellular glutathione (GSH/GSSG) through l-cysteine production. Because redox homeostasis can influence NO signaling, we hypothesized that CSE mediates E2 stimulation of UBF by modulating local intracellular cysteine metabolism and GSH/GSSG levels to promote redox homeostasis. Using non-pregnant ovariectomized WT and CSE-null (CSE KO) mice, we performed micro-ultrasound of mouse uterine and renal arteries to assess changes in blood flow upon exogenous E2 stimulation. We quantified serum and uterine artery NO metabolites (NOx), serum amino acids, and uterine and renal artery GSH/GSSG. WT and CSE KO mice exhibited similar baseline uterine and renal blood flow. Unlike WT, CSE KO mice did not exhibit expected E2 stimulation of UBF. Renal blood flow was E2-insensitive for both genotypes. While serum and uterine artery NOx were similar between genotypes at baseline, E2 decreased NOx in CSE KO serum. Cysteine was also lower in CSE KO serum, while citrulline and homocysteine levels were elevated. E2 and CSE deletion additively decreased GSH/GSSG in uterine arteries. In contrast, renal artery GSH/GSSG was insensitive to E2 or CSE deletion. Together, these findings suggest that CSE maintenance of uterine artery GSH/GSSG facilitates nitrergic signaling in uterine arteries and is required for normal E2 stimulation of UBF. These data have implications for pregnancy pathophysiology and the selective hormone responses of specific vascular beds. CSE-null mice exhibit abnormal estrogen augmentation of uterine artery blood flow. Estrogen lowers uterine artery nitric oxide metabolites in CSE null mice. CSE loss and estrogen additively impair uterine artery glutathione homeostasis. Neither CSE loss nor estrogen influences renal artery blood flow or glutathione.
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影响因子：
3.6
作者：
Guerra, Damian D.;Bok, Rachael;Hurt, K. Joseph
通讯作者：
Hurt, K. Joseph
影响因子：
1.8
作者：
Honnens, Aenne;Weisser, Simone;Bollwein, Heinrich
通讯作者：
Bollwein, Heinrich
DOI：
10.1165/rcmb.2006-0329sm
发表时间：
2007-06-01
影响因子：
6.4
作者：
Ckless, Karina;van der Vliet, Albert;Janssen-Heininger, Yvonne
通讯作者：
Janssen-Heininger, Yvonne
影响因子：
3.6
作者：
Hemmings, DG;Veerareddy, S;Davidge, ST
通讯作者：
Davidge, ST
影响因子：
7.3
作者：
Guerra, Damian D.;Bok, Rachael;Hurt, K. Joseph
通讯作者：
Hurt, K. Joseph