J. Lipid Res.
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J. Lipid Res., doi:10.1194/jlr.M400313-JLR200
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Submitted on August 17, 2004
Revised on January 1, 2005
Accepted on December 17, 2004

Astrocytes produce and secrete fibroblast growth factor-1 that promotes production of apoE high density lipoprotein in a manner of autocrine action

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

Department of Biochemistry, Cell Biology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Aichi 467-8601

Corresponding Author: syokoyam{at}med.nagoya-cu.ac.jp

The astrocytes prepared by one-week secondary culture after one-month primary culture of the rat brain cells (M/W cells) synthesized and secreted apoE and cholesterol more than the astrocytes prepared by conventional one-week primary and one-week secondary culture (W/W cells) (Biochim. Biophys. Acta (2002) 1589, 261-272). M/W cells also highly expressed FGF-1 mRNA. FGF-1 was identified in the cell lysate of the both types of astrocytes, but M/W cells released it more into the culture medium. Immunostaining of FGF-1 and apoE revealed that both were 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 a greater amount of HDL. Pretreatment with a goat anti-FGF-1 antibody or heparin depleted the stimulatory activity of the M/W cell-conditioned medium. The presence of the anti-FGF-1 antibody in the culture medium suppressed apoE secretion by the M/W cells. Differential inhibition of signaling pathways suggested that FGF-1 stimulates apoE synthesis via the PI3K/Akt pathway. Thus, astocytes are capable of releasing FGF-1 that promotes apoE-HDL production by an autocrine mechanism. The results are consistent with our in vivo observation that astrocytes produce FGF-1 prior to the increase of apoE in the post-injury lesion of the mouse brain (Neurochemistry International (2004) 45: 23-30).,


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Y. Nagayasu, J.-i. Ito, T. Nishida, and S. Yokoyama
Reactivity of Astrocytes to Fibroblast Growth Factor-1 for Biogenesis of Apolipoprotein E-High Density Lipoprotein is Down-regulated by Long-time Secondary Culture
J. Biochem., May 1, 2008; 143(5): 611 - 616.
[Abstract] [Full Text] [PDF]

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 J. Lipid Res.Home page
J.-i. Ito, Y. Nagayasu, K. Okumura-Noji, R. Lu, T. Nishida, Y. Miura, K. Asai, A. Kheirollah, S. Nakaya, and S. Yokoyama
Mechanism for FGF-1 to regulate biogenesis of apoE-HDL in astrocytes
J. Lipid Res., September 1, 2007; 48(9): 2020 - 2027.
[Abstract] [Full Text] [PDF]


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