The role of extracellular matrix metalloproteinase inducer on the action of dihydrotestosterone against the cellular damage induced by A beta(42)
The role of extracellular matrix metalloproteinase inducer on the action of dihydrotestosterone against the cellular damage induced by A beta(42)
复制标题
细胞外基质金属蛋白酶诱导剂对二氢睾酮对抗 A beta 诱导的细胞损伤作用的作用(42)
DOI：
10.1016/j.mce.2019.110536
复制
发表时间：
2019
影响因子：
4.1
通讯作者：
Cui Huixian
中科院分区：
文献类型：
--
作者：
Du Juan;Li Sha;Su Yuhong;Wang Haidong;Liu Hanjie;Cui Huixian
临床研究表明，男性患阿尔茨海默病（AD）的风险会因年龄相关的雄激素耗竭而增加。AD患者脑内β-淀粉样蛋白（Aβ）水平升高，Aβ被认为在AD的病理过程中起重要作用。一些研究表明雄激素通过调节Aβ代谢影响AD风险，但机制尚不清楚。在这项研究中，我们研究了细胞外基质金属蛋白酶诱导剂（CD 147）在这一行动中的作用。最初，我们证明雄激素正调控成年雄性大鼠和SH-SY 5 Y细胞中CD 147的表达。此外，这种调节可能涉及雄激素受体（AR）。此外，干扰CD 147表达降低了培养基中Aβ的清除率，并降低了细胞活力。对细胞形态及凋亡相关蛋白的表达也有影响。最后，我们发现干扰CD 147的表达阻断了双氢睾酮（DHT）诱导的Aβ减少和细胞保护作用。DHT通过CD 147调节MMP-2的表达。总之，这些结果表明，雄激素对Aβ的调节和细胞保护可能受到干扰CD 147表达的影响。
Clinical studies have revealed that the risk of Alzheimer's disease (AD) in men is increased by age-related androgen depletion. The level of β-amyloid (Aβ) is elevated in the brains of AD patients, and Aβ is believed to play a critical role in the pathology of AD. Some studies have indicated that androgens affect AD risk by regulating the metabolism of Aβ by an unclear mechanism. In this study, we investigated the role of the extracellular matrix metalloproteinase inducer (CD147) in this action. Initially, we demonstrated that androgens positively regulate the expression of CD147 in adult male rats and SH-SY5Y cells. Furthermore, this regulation may involve androgen receptor (AR). Additionally, interference of CD147 expression decreased the clearance of Aβ in culture medium and reduced cell viability. It also affected the morphology of the cells and the expression of apoptosis-related proteins. Finally, we found that interference of CD147 expression blocked the dihydrotestosterone (DHT)-induced reduction in Aβ and the protection of cells. DHT regulates MMP-2's expression through CD147. Together, these results imply that androgen regulation of Aβ and cell protection may be affected by interfering with the expression of CD147.