17β-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic Female Mice.
17β-Estradiol Suppresses Gastric Inflammatory and Apoptotic Stress Responses and Restores nNOS-Mediated Gastric Emptying in Streptozotocin (STZ)-Induced Diabetic Female Mice.
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DOI：
10.3390/antiox12030758
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发表时间：
2023-03-20
期刊：
影响因子：
7
通讯作者：
Gangula, Pandu
中科院分区：
文献类型：
--
作者：
Sprouse, Jeremy;Sampath, Chethan;Gangula, Pandu
关键词：
胃轻瘫（Gp）是糖尿病（DM）的严重并发症，主要见于女性。其特点是胃排空异常，胃内无机械阻塞。一氧化氮（NO）是由神经元一氧化氮合酶（nNOS）产生的一种抑制性神经递质。它在胃肠运动和胃排空中起着至关重要的作用。在这里，我们想证明补充17β-雌二醇（E2）对no介导的胃功能的保护作用。我们发现补充E2可以减轻链脲佐菌素（STZ）诱导的糖尿病雌性小鼠的氧化和炎症应激。我们的研究结果表明，每日给予治疗剂量的E2有利于代谢稳态。这种恢复是通过调节糖原合成酶激酶3β (GSK-3β)、核因子-红细胞2 p45相关因子2 （Nrf2）、II期酶、活化B细胞MAPK-和核因子kappa-轻链增强子（NFkB）介导的炎症细胞因子（IL-1β、IL-6、TNFα、IGF-1）和胃凋亡调节因子的表达/功能发生的。我们还发现补充E2可以提高雌性糖尿病小鼠的GCH-1蛋白水平。由于GCH-1促进四氢生物蝶呤（BH4， nNOS的辅助因子）的产生，糖尿病小鼠中GCH-1蛋白水平的升高可能改善其GE和氮能功能。我们的研究结果为雌激素在Gp背景下对胃氧化应激和细胞内炎症级联反应的影响提供了新的见解。
Gastroparesis (Gp) is a severe complication of diabetes mellitus (DM) observed predominantly in women. It is characterized by abnormal gastric emptying (GE) without mechanical obstruction in the stomach. Nitric oxide (NO) is an inhibitory neurotransmitter produced by neuronal nitric oxide synthase (nNOS). It plays a critical role in gastrointestinal (GI) motility and stomach emptying. Here, we wanted to demonstrate the protective effects of supplemental 17β-estradiol (E2) on NO-mediated gastric function. We showed E2 supplementation to alleviate oxidative and inflammatory stress in streptozotocin (STZ)-induced diabetic female mice. Our findings suggest that daily administration of E2 at therapeutic doses is beneficial for metabolic homeostasis. This restoration occurs via regulating and modulating the expression/function of glycogen synthase kinase-3β (GSK-3β), nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), Phase II enzymes, MAPK- and nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB)-mediated inflammatory cytokines (IL-1β, IL-6, TNFα, IGF-1), and gastric apoptotic regulators. We also showed E2 supplementation to elevate GCH-1 protein levels in female diabetic mice. Since GCH-1 facilitates the production of tetrahydrobiopterin (BH4, cofactor for nNOS), an increase in GCH-1 protein levels in diabetic mice may improve their GE and nitrergic function. Our findings provide new insights into the impact of estrogen on gastric oxidative stress and intracellular inflammatory cascades in the context of Gp.
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影响因子：
2.9
作者：
Heine, Christian L.;Kolesnik, Bernd;Schmidt, Renate;Werner, Ernst R.;Mayer, Bernd;Gorren, Antonius C. F.
通讯作者：
Gorren, Antonius C. F.
氧化应激诱导的细胞凋亡对 MLO-Y4 细胞中活性 FGF23 水平的影响：17-β-雌二醇的保护作用。
影响因子：
5.6
作者：
Domazetovic V;Falsetti I;Ciuffi S;Iantomasi T;Marcucci G;Vincenzini MT;Brandi ML
通讯作者：
Brandi ML
影响因子：
--
作者：
Culbreth M;Aschner M
通讯作者：
Aschner M
影响因子：
7.5
作者：
Al Hroob, Amir M.;Abukhalil, Mohammad H.;Mahmoud, Ayman M.
通讯作者：
Mahmoud, Ayman M.
影响因子：
2.4
作者：
Sprouse J;Sampath C;Gangula PR
通讯作者：
Gangula PR