Up-regulation of Glucosylceramide Synthesis upon Stimulation of Axonal Growth by Basic Fibroblast Growth Factor
Up-regulation of Glucosylceramide Synthesis upon Stimulation of Axonal Growth by Basic Fibroblast Growth Factor
复制标题
碱性成纤维细胞生长因子刺激轴突生长上调葡萄糖神经酰胺合成
DOI：
10.1074/jbc.275.14.9905
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
A. Futerman
中科院分区：
文献类型：
--
作者：
S. Boldin;A. Futerman
我们先前已经表明，碱性成纤维细胞生长因子（bFGF）和层粘连蛋白刺激培养的海马神经元中的轴突生长需要持续的葡糖神经酰胺（GlcCer）合成（Boldin，S.，和Futerman，A. H.等人（1997）J. Neurochem. 68，882-885）。我们现在证明，bFGF刺激轴突生长导致GlcCer合成速率增加。在与bFGF孵育的几分钟内，检测到[14 C]己酰基神经酰胺代谢为[14 C]己酰基GlcCer的速率显著增加，但[14 C]己酰基鞘磷脂合成的速率没有变化。GlcCer合成酶活性的体外分析显示，与bFGF或层粘连蛋白孵育后，[14 C]己酰GlcCer合成速率增加约2倍;其他生长因子对轴突生长速率没有影响，对[14 C]己酰GlcCer合成速率没有影响。[14 C]己酰GlcCer合成的增加速率不受放线菌酮或放线菌素预孵育的影响，并且没有检测到GlcCer合酶mRNA水平的升高，这表明GlcCer合酶通过翻译后机制上调。这些结果的相关性，了解轴突生长的调节进行了讨论。
We have previously shown that ongoing glucosylceramide (GlcCer) synthesis is required for basic fibroblast growth factor (bFGF) and laminin to stimulate axonal growth in cultured hippocampal neurons (Boldin, S., and Futerman, A. H. (1997)J. Neurochem. 68, 882–885). We now demonstrate that stimulation of axonal growth by bFGF leads to an increase in the rate of GlcCer synthesis. Within minutes of incubation with bFGF, a significant increase in the rate of metabolism of [14C]hexanoyl ceramide to [14C]hexanoyl GlcCer is detected, but there are no changes in the rate of [14C]hexanoyl sphingomyelin synthesis. In vitro analysis of GlcCer synthase activity revealed an approximately 2-fold increase in the rate of [14C]hexanoyl GlcCer synthesis upon incubation with either bFGF or laminin; other growth factors, which did not effect the rate of axon growth, had no effect on the rate of [14C]hexanoyl GlcCer synthesis. The increased rate of [14C]hexanoyl GlcCer synthesis was not affected by preincubation with either cycloheximide or actinomycin, and no elevation of GlcCer synthase mRNA levels was detected, suggesting that GlcCer synthase is up-regulated by a post-translational mechanism. The relevance of these results for understanding the regulation of axonal growth is discussed.
DOI：
10.1016/s0021-9258(19)38937-9
发表时间：
1990-05
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Futerman;B. Stieger;B. Stieger;A. Hubbard;R. Pagano
通讯作者：
A. Futerman;B. Stieger;B. Stieger;A. Hubbard;R. Pagano
使用 N-([1-14C]己酰基)-D-赤型鞘脂来测定鞘脂代谢。
影响因子：
--
作者：
Futerman,AH;Pagano,RE
通讯作者：
Pagano,RE
大鼠葡萄糖神经酰胺合酶的组氨酸-193 位于 UDP-葡萄糖和抑制剂 (D-threo-1-苯基-2-癸酰氨基-3-吗啉代丙烷-1-ol) 结合区域：一项生化和突变研究。
DOI：
--
发表时间：
1999
期刊：
The Biochemical journal
影响因子：
--
作者：
Wu,K;Marks,DL;Watanabe,R;Paul,P;Rajan,N;Pagano,RE
通讯作者：
Pagano,RE