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Genistein regulates calcium and phosphate homeostasis without activation of MEK 1/2 signalling pathway in an animal model of the andropause
Annals of Anatomy ( IF 2.2 ) Pub Date : 2021-09-23 , DOI: 10.1016/j.aanat.2021.151836
Jasmina Živanović 1 , Ivana Jarić 2 , Vladimir Ajdžanović 1 , Marko Miler 1 , Sanja Stanković 3 , Verica Milošević 1 , Branko Filipović 1
Affiliation  

Soy isoflavone genistein interplays with numerous physiological or pathophysiological processes during ageing. However, its protective role and underlying mechanisms of action in the regulation of calcium (Ca2+) and phosphate (Pi) homeostasis in an animal model of the andropause are yet to be fully clarified. Wistar male rats (16-month-old) were divided into sham-operated, orchidectomized, orchidectomized estradiol-treated (0.625 mg/kg b.m./day) and orchidectomized genistein-treated (30 mg/kg b.m./day) groups. Treatments were administered subcutaneously for 3 weeks, while the controls received vehicle alone. Estradiol treatment increased the expression level of fibroblast growth factor receptor (FGFR) and parathyroid hormone 1 receptor (PTH1R), and activated mitogen – activated protein kinase kinase 1/2 (MEK 1/2) signaling pathway in the kidneys. Genistein application induced a prominent gene and protein expression of Klotho and downregulated the expression of FGFR and PTH1R in the kidney of andropausal rats. Activation of protein kinase B (Akt) signalling pathway was observed, while MEK 1/2 signaling pathway wasn't altered after genistein treatment. The increase of 25 (OH) vitamin D in the serum and decrease in Ca2+ urine content was observed after genistein application. Our findings strongly suggest genistein as a potent biocompound with beneficial effects on the regulation of Ca2+ and Pi homeostasis, especially during aging process when the balance of mineral metabolism is impaired. These novel data provide closer insights into the physiological roles of genistein in the regulation of mineral homeostasis.



中文翻译:

在男性更年期动物模型中,染料木黄酮在不激活 MEK 1/2 信号通路的情况下调节钙和磷酸盐稳态

大豆异黄酮染料木素在衰老过程中与许多生理或病理生理过程相互作用。然而,它在调节钙(Ca 2+) 和磷酸盐 (Pi) 在男性更年期动物模型中的稳态尚未完全阐明。将 Wistar 雄性大鼠(16 个月大)分为假手术组、切除睾丸组、切除睾丸组的雌二醇治疗组(0.625 mg/kg bm/天)和切除睾丸组的染料木黄酮治疗组(30 mg/kg bm/天)。皮下给予治疗3周,而对照组仅接受载体。雌二醇治疗增加了肾脏中成纤维细胞生长因子受体 (FGFR) 和甲状旁腺激素 1 受体 (PTH1R) 的表达水平,并激活了丝裂原 - 活化蛋白激酶激酶 1/2 (MEK 1/2) 信号通路。金雀异黄素的应用诱导了 Klotho 的显着基因和蛋白质表达,并下调了雄性绝经大鼠肾脏中 FGFR 和 PTH1R 的表达。观察到蛋白激酶 B (Akt) 信号通路的激活,而 MEK 1/2 信号通路在染料木黄酮处理后没有改变。血清中 25 (OH) 维生素 D 的增加和 Ca 的减少施用染料木黄酮后观察到2+尿含量。我们的研究结果强烈表明染料木黄酮是一种有效的生物化合物,对调节 Ca 2+和 Pi 稳态具有有益作用,尤其是在矿物质代谢平衡受损的衰老过程中。这些新数据为染料木素在调节矿物质稳态中的生理作用提供了更深入的见解。

更新日期:2021-10-09
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