AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase

Oakhill, Jonathan S.; Steel, Rohan; Chen, Zhiping; Scott, John W.; Ling, Naomi X.Y.; Tam, Shanna; Kemp, Bruce E.

doi:10.1126/science.1200094

Cited by 514 publications

(427 citation statements)

References 27 publications

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“…AMPK activates a number of energy-producing metabolic pathways, but it also inhibits energy-consuming pathways [11] . AMPK has been termed a 'fuel gauge' for cellular energy levels because of this dual effect [9][10][11][12] . The role of AMPK as a fuel gauge is particularly relevant in the heart, which has a remarkably high demand for energy.…”

Section: Discussionmentioning

confidence: 99%

“…AMPK activity requires the phosphorylation of the alpha subunit on Thr 172 in its activation loop by one or more upstream kinases (AMPKKs) [11] . AMPK phosphorylation downregulates ATP-consuming processes, such as the synthesis of fatty acids, cholesterol, and protein, but it also upregulates ATP-producing catabolic pathways, such as fatty acid oxidation and glucose uptake [11,12] . However, the role of AMPK in PRIS is not known.…”

Section: Introductionmentioning

confidence: 99%

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Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

et al. 2011

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Aim: To explore the mechanisms underlying the propofol infusion syndrome (PRIS), a potentially fatal complication during prolonged propofol infusion. Methods: Male rabbits under mechanical ventilation through endotracheal intubation were divided into 3 groups (n=6 for each) that were sedated with 1% propofol (Group P), isoflurane (Group I) or isoflurane while receiving 10% intralipid (Group II), respectively. Blood biochemical parameters were collected at 0, 6, 12, 18, 24, and 30-36 h after the initiation of treatments. The hearts were removed out immediately after the experiments, and the level of tumor necrosis factor (TNF)-α in the hearts were studied using immunohistochemistry. AMP-activated protein kinase (AMPK) and phospho-AMPK in the hearts were assessed using Western blotting. Results: The mortality rate was 50% in Group P, and 0% in Groups I and II. The serum lipids and liver function indices in Group P were significantly increased, but moderately increased in Group II. Significant decreases in these indices were found in Groups I. All the groups showed dramatically increased release of creatine kinase (CK). Intense positive staining of TNF-α was found in all the heart samples in Group P, but only weak and neglectful staining was found in the hearts from Group II and Group I, respectively. AMPK phosphorylation was significantly increased in the hearts of Group P. Conclusion: Continuous infusion of large dose of propofol in rabbits undergoing prolonged mechanical ventilation causes hyperlipidemia, liver dysfunction, increased CK levels, AMPK activation and myocardial injury. The imbalance between energy demand and utilization may contribute to PRIS.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

et al. 2011

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“…The two hexokinases, HEX-A and HEX-C, potentially affect the ADP/ATP ratio and have different tissue expressions. They could vary the ADP/ATP content, and in that fashion set energy-state response via regulating AMPK signalling [54][55][56]. This AMP-activated kinase is a sensor that has effects in Drosophila [57,58], which provides a link between lifespan and caloric restriction [59].…”

Section: Discussionmentioning

confidence: 99%

Genetic perturbation of key central metabolic genes extends lifespan in Drosophila and affects response to dietary restriction

Talbert¹,

Barnett²,

Hoff³

et al. 2015

Proc. R. Soc. B.

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There is a connection between nutrient inputs, energy-sensing pathways, lifespan variation and aging. Despite the role of metabolic enzymes in energy homeostasis and their metabolites as nutrient signals, little is known about how their gene expression impacts lifespan. In this report, we use P-element mutagenesis in Drosophila to study the effect on lifespan of reductions in expression of seven central metabolic enzymes, and contrast the effects on normal diet and dietary restriction. The major observation is that for five of seven genes, the reduction of gene expression extends lifespan on one or both diets. Two genes are involved in redox balance, and we observe that lower activity genotypes significantly extend lifespan. The hexokinases also show extension of lifespan with reduced gene activity. Since both affect the ATP/ADP ratio, this connects with the role of AMP-activated protein kinase as an energy sensor in regulating lifespan and mediating caloric restriction. These genes possess significant expression variation in natural populations, and our experimental genotypes span this level of natural activity variation. Our studies link the readout of energy state with the perturbation of the genes of central metabolism and demonstrate their effect on lifespan.

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“…AMP-activated kinase (AMPK) is a heterotrimeric protein exquisitely sensitive to variations in AMP and, as recently found, ADP levels (Oakhill et al, 2011). Upon nutrient deprivation, AMPK becomes activated and downregulates ATP-consuming processes and upregulates the ATP-generating ones.…”

Section: The Metabolic Pattern Of Cancer Cellsmentioning

confidence: 99%

Metabolic reprogramming of the tumor

2012

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Cancer is classically considered as a genetic and, more recently, epigenetic multistep disease. Despite seminal studies in the 1920s by Warburg showing a characteristic metabolic pattern for tumors, cancer bioenergetics has often been relegated to the backwaters of cancer biology. This review aims to provide a historical account on cancer metabolism research, and to try to integrate and systematize the metabolic strategies in which cancer cells engage to overcome selective pressures during their inception and evolution. Implications of this renovated view on some common concepts and in therapeutics are also discussed.

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AMPK Is a Direct Adenylate Charge-Regulated Protein Kinase

Cited by 514 publications

References 27 publications

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

Lipid metabolism disturbances and AMPK activation in prolonged propofol-sedated rabbits under mechanical ventilation

Genetic perturbation of key central metabolic genes extends lifespan in Drosophila and affects response to dietary restriction

Metabolic reprogramming of the tumor

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