AMPK

stable and permanent cell line from methylcholanthrene-induced pectoralis fibrosarcomas of Japanese quail Cotumix cotumix Japonica developed by Antin and Ordahl, was used in this study. QT6 cells were grown in McCoy medium supplemented with 10% foetal calf serum and 1 % chicken serum to 80-90% confluence, fasted 16 h in serum-free medium, washed once with PBS and incubated for 2 h in different media varying in glucose (1 to 3 g/1 of glucose) and/or amino acid concentrations (0.5x to 2x). Cell samples were stored at -80 °C until further analysis. 

In conclusion, our preliminary results suggest that nutrients, in particular amino acids, seem to be involved in the regulation of the AMPK pathway. Optimizing their supply could be a tool for controlling muscle glycogen store. 

Sante-Lhoutellier, C. Amould, B. Boutten, N. Sellier, E. Baeza, N. JeU, Y. Jego, M. J. Duclos and E. Le Bihan-Duval, 2005. Variations in chicken breast meat quality implications of struggle and muscle glycogen content at death. Br Poult Sci. 46, 572-579. 

Carling, D. and D.G. Hardie, 1989. The substrate and sequence specificity of the AMP-activated protein kinase. 

de Beer, R. W. Rosebrough, M.P. Richards, J.P. McMurtryP and C.N. Coon University of Arkansas, Center of Excellence for Poultry Science, Fayetteville, Arkansas 72701, USA Aviagen, 5015 Bradford Dr, Huntsville, Alabama 35805, USA 

---

Aminoimidazole-4-carboxamide ribonucleoside (also known as AICA riboside or AICAR). An adenosine analogue that is taken up into cells by adenosine transporters and converted by adenosine kinase to the monophosphorylated nucleotide form, ZMP. ZMP is an analogue of AMP that activates the AMP-activated protein kinase (AMPK), for which acadesine or AICAR can be used as a pharmacological activator. 

AMP-activated protein kinase, AMPK SNF1 complex (fungi) SNF1-related kinase-1 (higher plants)... 

Both effects of AMP (inhibition of dephosphorylation and activation) are antagonized by high concentrations of ATP, which compete with AMP for binding at the Bateman domains. Thus, the AMPK system can monitor changes in the cellular AMP ATP ratio. 

As well as the activation of AMPK by increases in cellular AMP ATP, due to phosphorylation by LKB1,... 

AMPK can also be activated by a Ca2+-mediated pathway involving phosphorylation at Thr-172 by the Ca2+/calmodulin-dependent protein kinase, CaMKK 3. CaMKKa and CaMKK 3 were discovered as the upstream kinase for the calmodulin-dependent protein kinases-1 and -IV they both activate AMPK in a Ca2+/ calmodulin-dependent manner in cell-free assays, although CaMKK 3 appears to much more active against AMPK in intact cells. Expression of CaMKKa and CaMKK(3 primarily occurs in neural tissues, but CaMKKp is also expressed in some other cell types. Thus, the Ca2+-mediated pathway for AMPK activation has now been shown to occur in response to depolarization in rat neuronal tissue, in response to thrombin (acting via a Gq-coupled receptor) in endothelial cells, and in response to activation of the T cell receptor in T cells. 

AMPK is also regulated by a number of cytokines, including adipokines secreted from adipocytes that... 

Once activated, the AMPK system switches on catabolic pathways that generate ATP (upper entries in Table 2), such as the uptake and oxidation of fatty... 

The first pharmacological agent shown to activate AMPK was 5-aminoimidazole-4-carboxamide (AICA) riboside, also known as acadesine. This adenosine analogue is taken up into cells by adenosine transporters and phosphoiylated by adenosine kinase to the mono-phosphorylated form, AICA ribotide or ZMP. ZMP accumulates inside cells to higher concentrations than the concentration of AICA riboside present in the medium, and it mimics both effects of AMP on AMPK system (allosteric activation and inhibition of... 

AMP-activated Protein Kinase. Table 2 Metabolic effects of AMPK activation. In cases marked with an asterisk, there is evidence that AMPK mediates its effects by modulating the target named, although it is not yet clear whether the protein is directly phosphorylated by AMPK... 

Hardie DG, Sakamoto K (2006) AMPK a key sensor of fuel and energy status in skeletal muscle. Physiology (Bethesda) 21 48-60... 

Figure 21-6. Regulation of acetyl-CoA carboxylase by phosphorylation/dephosphorylation.The enzyme is inactivated by phosphorylation by AMP-activated protein kinase (AMPK), which in turn is phosphorylated and activated by AMP-activated protein kinase kinase (AMPKK). Glucagon (and epinephrine), after increasing cAMP, activate this latter enzyme via cAMP-dependent protein kinase. The kinase kinase enzyme is also believed to be activated by acyl-CoA. Insulin activates acetyl-CoA carboxylase, probably through an "activator" protein and an insulin-stimulated protein kinase.

PD098059 PD184352 MEK1/2 (ERK pathway) MEK1/2 (ERK pathway) (Alessi et al., 1995 Dudley et al, 1995) (Davies et al., 2000) Also inhibits MEK5 (Kamakura et al., 1999) and activates AMPK (Dokladda et al., 2005)... 

Figure 25.3 Presentation of estradiol to A. endothelial cells affects signaling. (A) Physiological levels of estradiol (E2) complexed with albumin do not elicit the production of nitric oxide when presented to cultured endothelial cells although E2-albumin binds to caveolar SR-B1. (B) Physiological levels of estradiol complexed with HDL elicit the production of nitric oxide by activating AMPK and then eNOS. Although it is depicted in this figure that AMPK is activated by binding of estradiol to the estrogen receptor, B. this mechanism has not been experimentally demonstrated. Other mechanisms of E2-HDL activation of AMPK and eNOS are thus possible (See also color insert).

---