ASTROCYTES REGULATE alpha-SECRETASE-CLEAVED SOLUBLE AMYLOID PRECURSOR PROTEIN SECRETION IN NEURONAL CELLS: INVOLVEMENT OF GROUP IIA SECRETORY PHOSPHOLIPASE A(2)

摘要

Astrocytes are major supportive cells in brains with important functions including providing nutrients and regulating neuronal activities. In this study, we demonstrated that astrocytes regulate amyloid precursor protein (APP) processing in neuronal cells through secretion of group IIA secretory phospholipase A(2) (sPLA(2)-IIA). When astrocytic cells (DITNC) were mildly stimulated with the pro-inflammatory cytokines, such as TNF alpha and IL-1 beta, sPLA(2)-IIA was secreted into the medium. When conditioned medium containing sPLA(2)-IIA was applied to human neuroblastoma (SH-SY5Y) cells, there was an increase in both cell membrane fluidity and secretion of alpha-secretase-cleaved soluble amyloid precursor protein (sAPP alpha). These changes were abrogated by KH064, a selective inhibitor of sPLA(2)-IIA. In addition, exposing SH-SY5Y cells to recombinant human sPLA(2)-IIA also increased membrane fluidity, accumulation of APP at the cell surface, and secretion of sAPP alpha, but without altering total expressions of APP, alpha-secretases and beta-site APP cleaving enzyme (BACE1). Taken together, our results provide novel information regarding a functional role of sPLA(2)-IIA in astrocytes for regulating APP processing in neuronal cells. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.