AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?
AMPK: opposing the metabolic changes in both tumour cells and inflammatory cells?
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DOI：
10.1042/bst20120351
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发表时间：
2013-04
影响因子：
3.9
通讯作者：
Hardie DG
中科院分区：
文献类型：
--
作者：
Dandapani M;Hardie DG
AMP激活的蛋白激酶（AMPK）是细胞能量状态的传感器，似乎已经出现在早期真核生物进化过程中。在单细胞真核生物酿酒酵母中，AMPK直向同源物被葡萄糖饥饿激活，并且当葡萄糖低时，从糖酵解（发酵）到氧化代谢的转换需要AMPK。在哺乳动物中，快速增殖的细胞（包括肿瘤细胞）和参与炎症的免疫细胞都倾向于利用快速葡萄糖摄取和糖酵解（称为瓦尔堡效应或有氧糖酵解），而不是氧化代谢来满足其对ATP的高需求。由于哺乳动物AMPK与其酵母同源物一样，倾向于以糖酵解为代价促进更节能的氧化代谢，因此可以预期激活AMPK的药物将抑制细胞增殖并因此抑制癌症，以及发挥抗炎作用。支持这一观点的证据进行了讨论，包括我们最近的研究结果，AMPK激活的经典抗炎药，水杨酸。
The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that appears to have arisen during early eukaryotic evolution. In the unicellular eukaryote Saccharomyces cerevisiae, the AMPK orthologue is activated by glucose starvation and is required for the switch from glycolysis (fermentation) to oxidative metabolism when glucose runs low. In mammals, rapidly proliferating cells (including tumour cells) and immune cells involved in inflammation, both tend to utilize rapid glucose uptake and glycolysis (termed the Warburg effect or aerobic glycolysis) rather than oxidative metabolism to satisfy their high demand for ATP. Since mammalian AMPK, like its yeast orthologue, tends to promote the more energy-efficient oxidative metabolism at the expense of glycolysis, it might be expected that drugs that activate AMPK would inhibit cell proliferation and and hence cancer, as well as exerting anti-inflammatory effects. Evidence supporting this view is discussed, including our recent findings that AMPK is activated by the classical anti-inflammatory drug, salicylate.