title: Astrocytes regulate α-secretase-cleaved soluble amyloid precursor protein secretion in neuronal cells: Involvement of group IIA secretory phospholipase A2.
abstract: 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 A2 (sPLA2-IIA). When astrocytic cells (DITNC) were mildly stimulated with the pro-inflammatory cytokines, such as TNF α and IL-1β, sPLA2-IIA was secreted into the medium. When conditioned medium containing sPLA2-IIA was applied to human neuroblastoma (SH-SY5Y) cells, there was an increase in both cell membrane fluidity and secretion of α-secretase-cleaved soluble amyloid precursor protein (sAPPα). These changes were abrogated by KH064, a selective inhibitor of sPLA2-IIA. In addition, exposing SH-SY5Y cells to recombinant human sPLA2-IIA also increased membrane fluidity, accumulation of APP at the cell surface, and secretion of sAPPα, but without altering total expressions of APP, α-secretases and β-site APP cleaving enzyme (BACE1). Taken together, our results provide novel information regarding a functional role of sPLA2-IIA in astrocytes for regulating APP processing in neuronal cells.
authors.affiliation: Hope Center for Neurological Disorders and Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, United States.
authors.forename: X
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, United States.
authors.forename: W
authors.initials: W
authors.lastname: Sheng
authors.affiliation: Department of Bioengineering, University of Missouri, Columbia, MO 65211, United States.
authors.forename: D M
authors.initials: DM
authors.lastname: Ridgley
authors.affiliation: College of Engineering, Driftmier Engineering Center, University of Georgia, Athens, GA 30602, United States.
authors.forename: M A
authors.initials: MA
authors.lastname: Haidekker
authors.affiliation: Department of Biochemistry, University of Missouri, Columbia, MO 65211, United States.
authors.forename: G Y
authors.initials: GY
authors.lastname: Sun
authors.affiliation: Department of Bioengineering, University of Missouri, Columbia, MO 65211, United States; Department of Bioengineering, University of Illinois at Chicago, Chicago, IL 60607, United States. Electronic address: leejam@missouri.edu.
authors.forename: J C
authors.initials: JC
authors.lastname: Lee
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002470:Cell Survival; D017077:Culture Media, Conditioned; D005455:Fluorescent Antibody Technique; D054501:Group II Phospholipases A2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D008560:Membrane Fluidity / Q000187:drug effects / Q000502:physiology; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D017077:Culture Media, Conditioned; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D054501:Group II Phospholipases A2; D053829:Amyloid Precursor Protein Secretases
keywords: SH-SY5Y; astrocytes; cytokine; membrane fluidity; sAPP(α); sPLA(2)-IIA