title: Distinct roles of sAPP-α and sAPP-β in regulating U251 cell differentiation.
abstract: Sequential cleavages of APP by β-secretase and γ-secretase release β-amyloid (Aβ) and one secreted form of APP (sAPP-β) in Alzheimer' s disease (AD). Alternatively, in non-pathological situations, APP is predominantly cleaved by α-secretase within the amyloid sequence, to release the other soluble form of APP, sAPP-α. However, the functions of the two types of sAPP are still unclear. We performed this study to compare the function of sAPP-α and sAPP-β in differentiation of the glioma cell line U251. We found that sAPP-α suppressed astrocytic differentiation and promoted neuronal differentiation in U251 cells. Additionally, sAPP-α enhanced U251 terminal differentiation into a cholinergic-like neuronal phenotype. In contrast, sAPP-β suppressed neuronal differentiation and promoted the astrocytic differentiation of U251 cells. These findings could not only enrich the knowledge of the potential physiological function of sAPP-α and sAPP-β, but also indicate that they may be connected to the pathological mechanism of AD. Furthermore, these findings suggest that new strategies, such as increasing the level of sAPP-α and/or decreasing the level of sAPP-β in brain, or transplanting stem cells with increased sAPP-α and/or decreased sAPP-β, may have potential value for AD treatment.
authors.affiliation: Research Center of Developmental Biology, Department of Histology and Embryology, College of Basic Medical Sciences, Second Military Medical University, Shanghai, People' s Republic of China.
authors.forename: Junfeng
authors.initials: J
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.forename: Lixing
authors.initials: L
authors.lastname: Fan
authors.forename: Qiaoling
authors.initials: Q
authors.lastname: Wang
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Xu
authors.forename: Qing
authors.initials: Q
authors.lastname: Sun
authors.forename: Houqi
authors.initials: H
authors.lastname: Liu
mesh_terms: D016564:Amyloid beta-Protein Precursor / Q000378:metabolism / Q000502:physiology*; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D045744:Cell Line, Tumor; D005910:Glioma / Q000737:chemistry / Q000473:pathology; D006131:Growth Inhibitors / Q000502:physiology; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; D006131:Growth Inhibitors