Study summary · research use only
Nucleosides block AICAR-stimulated activation of AMPK in skeletal muscle and cancer cells
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
In this cell-based laboratory study (species not specified), the effect of nucleoside-containing culture media on AICAR-stimulated activation of AMP-activated kinase (AMPK) was examined in skeletal muscle and cancer cells. The authors report that in nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake, and suppressed cell proliferation, but that these effects were blunted or blocked in media such as minimal essential medium α (MEMα) that contain adenosine and other nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action, and MEMα blocked AICAR-stimulated AMPK activation even with methotrexate present. Other media components, including vitamin B-12, vitamin C, and α-lipoic acid, had a minor modulatory effect, and the findings highlight a role for extracellular nucleosides and nucleoside transporters in AMPK regulation.
Abstract
AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR), an adenosine analog, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as minimal essential medium α (MEMα), contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake, and suppressed cell proliferation. Conversely, these effects were blunted or completely blocked in MEMα that contains nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action. MEMα with nucleosides blocked AICAR-stimulated AMPK activation even in the presence of methotrexate, which normally markedly enhances AICAR action by reducing its intracellular clearance. Other common media components, such as vitamin B-12, vitamin C, and α-lipoic acid, had a minor modulatory effect on AICAR action. Our findings show that nucleoside-containing media, commonly used in AMPK research, block action of the most widely used pharmacological AMPK activator AICAR. Results of cell-based assays in which AICAR is used for AMPK activation therefore critically depend on media formulation. Furthermore, our findings highlight a role for extracellular nucleosides and nucleoside transporters in regulation of AMPK activation.
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