title: Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action.
abstract: The astrocytes prepared by 1 week secondary culture after 1 month primary culture of rat brain cells (M/W cells) synthesized and secreted apolipoprotein E (apoE) and cholesterol more than the astrocytes prepared by conventional 1 week primary and 1 week secondary culture (W/W cells) (Ueno, S., J. Ito, Y. Nagayasu, T. Furukawa, and S. Yokoyama. 2002. An acidic fibroblast growth factor-like factor secreted into the brain cell culture medium upregulates apoE synthesis, HDL secretion and cholesterol metabolism in rat astrocytes. Biochim. Biophys. Acta. 1589: 261-272). M/W cells also highly expressed fibroblast growth factor-1 (FGF-1) mRNA. FGF-1 was identified in the cell lysate of both cell types, but M/W cells released more of it into the medium. Immunostaining of FGF-1 and apoE revealed that both localized in the cells that produce glial fibrillary acidic protein. The conditioned media of M/W cells and FGF-1 stimulated W/W cells to release apoE and cholesterol to generate more HDL. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of M/W cell-conditioned medium. The presence of the anti-FGF-1 antibody in the medium suppressed apoE secretion by M/W cells. Differential inhibition of signaling pathways suggested that FGF-1 stimulates apoE synthesis via the phosphoinositide 3-OH kinase for PI3K/Akt pathway. Thus, astrocytes release FGF-1, which promotes apoE-HDL production by an autocrine mechanism. These results are consistent with our in vivo observation that astrocytes produce FGF-1 before the increase of apoE in the postinjury lesion of the mouse brain (Tada, T., J. Ito, M. Asai, and S. Yokoyama. 2004. Fibroblast growth factor 1 is produced prior to apolipoprotein E in the astrocytes after cryo-injury of mouse brain. Neurochem. Int. 45: 23-30).
authors.affiliation: Department of Biochemistry, Cell Biology, and Metabolism, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
authors.forename: Jin-ichi
authors.initials: J
authors.lastname: Ito
authors.forename: Yuko
authors.initials: Y
authors.lastname: Nagayasu
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.forename: Alireza
authors.initials: A
authors.lastname: Kheirollah
authors.forename: Michi
authors.initials: M
authors.lastname: Hayashi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000378:metabolism*; D019898:Autocrine Communication; D002478:Cells, Cultured; D008076:Cholesterol, HDL / Q000378:metabolism*; D017077:Culture Media, Conditioned / Q000378:metabolism; D016220:Fibroblast Growth Factor 1 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction
chemical_list: D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D017077:Culture Media, Conditioned; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1