Department of Endocrinology, Pathophysiology and Applied Biology, Inter-University Center for Research on Reproductive Health (CIRMAR), Center of Excellence on Neurodegenerative Diseases (CEND), Città Studi University of Milan, Via G. Balzaretti 9, 20133 Milan, Italy.
J Endocrinol Invest. 2011 Nov;34(10):e362-8. doi: 10.3275/7803. Epub 2011 Jun 21.
The 5'-AMP-activated protein kinase (AMPK) plays a fundamental role in regulating energy homeostasis as well as feeding and metabolism, through central and peripheral actions. AMPK is activated by conditions causing ATP depletion and by different metabolic molecules, such as adiponectin and AMPK agonist, such as 5-aminoimidazole- 4-carboxamide-1-β-D-ribofuranoside (AICAR). AMPK activation has also been shown to affect the migration of different cell types and to participate in the central control of reproductive function, although information concerning AMPK and the development of the hypothalamic reproductive compartment is lacking.
To explore whether AMPK activation by globular adiponectin (gAdipo) and AICAR may affect the migratory ability of GnRH neurons.
We used GN11 immature GnRH neurons (in vitro model system), RT-PCR and Western blot analysis, and Boyden's chamber assay.
gAdipo did not affect FBS-stimulated migration of GN11 cells and activated AMPK through the mandatory phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and Akt, which also interact one to each other. AICAR treatment inhibited FBS-stimulated GN11 cell migration, through a long-lasting activation of AMPK. A downstream activation of ERK1/2 by AICAR was also observed and inhibition of ERK1/2 amplified AICAR-induced inhibition of migration.
The direct, but not the indirect, activation of AMPK appears to negatively affect FBSinduced GN11 cell migration, suggesting that the final balance between pro-migratory and anti-migratory actions may also depend upon the specific sequence of intracellular signals activated by one agent.
5'-AMP 激活的蛋白激酶（AMPK）通过中枢和外周作用，在调节能量稳态以及摄食和代谢方面发挥着重要作用。AMPK 可被导致 ATP 耗竭的条件以及不同的代谢分子（如脂联素和 AMPK 激动剂，如 5-氨基咪唑-4-甲酰胺-1-β-D-核糖呋喃糖苷（AICAR））激活。AMPK 的激活还被证明会影响不同类型细胞的迁移，并参与生殖功能的中枢控制，尽管有关 AMPK 和下丘脑生殖区室发育的信息尚缺乏。
探讨球状脂联素（gAdipo）和 AICAR 激活 AMPK 是否会影响 GnRH 神经元的迁移能力。
我们使用了未成熟的 GnRH 神经元 GN11（体外模型系统）、RT-PCR 和 Western blot 分析以及 Boyden 室测定。
gAdipo 不会影响 FBS 刺激的 GN11 细胞迁移，而是通过强制磷酸化细胞外信号调节激酶 1 和 2（ERK1/2）和 Akt 来激活 AMPK，ERK1/2 和 Akt 也相互作用。AICAR 处理通过长期激活 AMPK 抑制了 FBS 刺激的 GN11 细胞迁移。还观察到 AICAR 对 ERK1/2 的下游激活，并且 ERK1/2 的抑制增强了 AICAR 诱导的迁移抑制。
AMPK 的直接而非间接激活似乎会对 FBS 诱导的 GN11 细胞迁移产生负面影响，这表明促迁移和抗迁移作用之间的最终平衡可能还取决于一种药物激活的特定细胞内信号序列。
