The role of extracellular matrix metalloproteinase inducer on the action of dihydrotestosterone against the cellular damage induced by Aβ42. (1st December 2019)

• Record Type: Journal Article
• Authors: Du, Juan; Li, Sha; Su, Yuhong; Wang, Haidong; Liu, Hanjie; Cui, Huixian
• Is Part Of: Molecular and cellular endocrinology. Volume 498(2019)
• Publication Date: 2019-12-01
• Subjects: β-amyloid -- Alzheimer's disease -- Dihydrotestosterone -- Extracellular matrix metalloproteinase inducer; Endocrinology -- Periodicals; Molecular biology -- Periodicals; Cytology -- Periodicals; Endocrinology -- Periodicals; Hormones -- Periodicals; Endocrinologie -- Périodiques; Cytology; Endocrinology; Molecular biology; Periodicals; 573.4
• DOI: 10.1016/j.mce.2019.110536
• Languages: English
• ISSNs: 0303-7207

Abstract

Abstract: 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. Highlights: Androgens regulate CD147 expression in the rat hippocampus. DHT regulates CD147 expression via androgen receptor in SH-SY5Y cells. Downregulation of CD147 expression inhibits the degradation of Aβ42 and promotes apoptosis. Depression of CD147 limits DHT's ability to degrade Aβ42 and to resist Aβ42 -induced apoptosis. DHT regulates MMP-2's expression through CD147.