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Journal of Biochemistry Advance Access published online on January 23, 2008
Journal of Biochemistry, doi:10.1093/jb/mvn008
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© 2008 The Japanese Biochemical Society

Reactivity of Astrocytes to Fibroblast Growth Factor-1 for Biogenesis of Apolipoprotein E-High Density Lipoprotein is Down-Regulated by Long-Time Secondary Culture

Yuko Nagayasu, Jin-ichi Ito, Tomo Nishida and Shinji Yokoyama*

Biochemistry, Nagoya City University Graduate School of Medical Sciences, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan

*To whom correspondence should be addressed. Telephone +81-52-853-8139, FAX +81- 52-841-3480, e-mail syokoyam{at}med.nagoya-cu.ac.jp

Received October 30, 2007; Accepted January 15, 2008


  Abstract

Astrocytes produce and release fibroblast growth fator-1 (FGF-1) upon one-month primary and one-week secondary culture (M/W cells) and stimulate themselves by an autocrine manner to produce apoE-high density lipoproteins (HDL) (BBA 1589: 261-272, JLR 46: 679-686), closely associated with their generation of apoE-HDL in brain injury (Neurochem. Int. 45:23-30). Astrocytes prepared by one-week primary and one-month secondary culture (W/M cells), however, expressed FGF-1 as much as M/W cells but produce apoE-HDL much less. The W/M cells conditioned medium in fact contained FGF-1 activity to stimulate astrocytes prepared by one-week primary and one-week-secondary culture (W/W cells). FGF-1 did not stimulate W/M cells for apoE-HDL biogenesis while it stimulated W/W cells. Phosphorylation of Akt, ERK and MEK were induced by FGF-1 in W/W cells (JLR 48: 2020-2027) but not in W/M cells. Finally, fibroblast growth factor receptor-1 in the membrane decreased in W/M cells in comparison to W/W cells. Interestingly, the reactivity of astrocytes to FGF-1 was recovered when W/M cells were transferred to the tertiary culture of one week. We concluded that astrocytes decrease their reactivity to FGF-1 for apoE-HDL biogenesis in certain conditions. The findings indicate astrocyte FGF-1 enhances biogenesis of apoE-HDL also by a paracrine mechanism.

Key Words: astrocytes, apolipoprotein E, high density lipoprotein, cholesterol, fibroblast growth factor 1


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