J. Lipid Res. Neurobiology of Lipids (ISSN1683-5506)
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Originally published In Press as doi:10.1194/jlr.M400313-JLR200 on January 1, 2005

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Journal of Lipid Research, Vol. 46, 679-686, April 2005
Copyright © 2005 by American Society for Biochemistry and Molecular Biology

Astrocytes produce and secrete FGF-1, which promotes the production of apoE-HDL in a manner of autocrine action

Jin-ichi Ito, Yuko Nagayasu, Rui Lu, Alireza Kheirollah, Michi Hayashi and Shinji Yokoyama1

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

1 To whom correspondence should be addressed. e-mail: syokoyam{at}med.nagoya-cu.ac.jp

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).

Abbreviations: apoE, apolipoprotein E; DPBS, Dulbecco's phosphate-buffered saline; FCS, fetal calf serum; FGF-1, fibroblast growth factor-1; GFAP, glial fibrillary acidic protein; PI3K, phosphoinositide 3-OH kinase; TBS, salined 0.02 Tris-Hcl buffer

Supplementary key words apolipoprotein E • fibroblast growth factor-1 • high density lipoprotein • brain damage • cholesterol


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