scholarly journals Fructose-2,6-Bisphosphate Is Lower in Copper Deficient Rat Cerebellum Despite Higher Content of Phosphorylated AMP-Activated Protein Kinase

2008 ◽  
Vol 233 (10) ◽  
pp. 1262-1270 ◽  
Author(s):  
Anna A. Gybina ◽  
Joseph R. Prohaska
Keyword(s):  
Protein Kinase ◽  
Brain Mitochondria ◽  
Anaerobic Glycolysis ◽  
Protein Abundance ◽  
Ampk Activation ◽  
Cellular Energy ◽  
Cu Deficiency ◽  
Rat Pups ◽  
Amp Activated Protein Kinase ◽  
Brain Lactate

Limitation in copper (Cu) leads to pathophysiology in developing brain. Cu deficiency impairs brain mitochondria and results in high brain lactate suggesting augmented anaerobic glycolysis. AMP activated protein kinase (AMPK) is a cellular energy “master-switch” that is thought to augment glycolysis through phosphorylation and activation phosphofructokinase 2 (PFK2) resulting in increases of the glycolytic stimulator fructose-2,6-bisphosphate (F2,6BP). Previously, Cu deficiency has been shown to augment cerebellar AMPK activation. Cerebella of Cu-adequate (Cu+) and Cu-deficient (Cu−) rat pups were assessed to evaluate if AMPK activation in Cu− cerebella functioned to enhance PFK2 activation and increase F2,BP concentration. Higher levels of pAMPK were detected in Cu− cerebella. However, PFK2 activity, mRNA, and protein abundance were not affected by Cu deficiency. Surprisingly, F2,6BP levels were markedly lower in Cu− cerebella. Lower F2,6BP may be due to inhibition of PFK2 by citrate, as citrate concentration was significantly higher in Cu− cerebella. Data suggest AMPK activation in Cu− cerebellum does not augment glycolysis through a PFK2 mechanism. Furthermore, other metabolite data suggest that glycolysis may actually be blunted, since levels of glucose and glucose-6-phosphate were higher in Cu− cerebella than controls.

scholarly journals Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes

2006 ◽  
Vol 203 (7) ◽  
pp. 1665-1670 ◽  
Author(s):  
Peter Tamás ◽  
Simon A. Hawley ◽  
Rosemary G. Clarke ◽  
Kirsty J. Mustard ◽  
Kevin Green ◽  
...  
Keyword(s):  
Protein Kinase ◽  
T Lymphocytes ◽  
Energy Homeostasis ◽  
Antigen Receptor ◽  
Adenosine Monophosphate ◽  
Ampk Activation ◽  
Serine Kinase ◽  
Cellular Energy ◽  
Amp Activated Protein Kinase ◽  
Stimulation Of

The adenosine monophosphate (AMP)–activated protein kinase (AMPK) has a crucial role in maintaining cellular energy homeostasis. This study shows that human and mouse T lymphocytes express AMPKα1 and that this is rapidly activated in response to triggering of the T cell antigen receptor (TCR). TCR stimulation of AMPK was dependent on the adaptors LAT and SLP76 and could be mimicked by the elevation of intracellular Ca2+ with Ca2+ ionophores or thapsigargin. AMPK activation was also induced by energy stress and depletion of cellular adenosine triphosphate (ATP). However, TCR and Ca2+ stimulation of AMPK required the activity of Ca2+–calmodulin-dependent protein kinase kinases (CaMKKs), whereas AMPK activation induced by increased AMP/ATP ratios did not. These experiments reveal two distinct pathways for the regulation of AMPK in T lymphocytes. The role of AMPK is to promote ATP conservation and production. The rapid activation of AMPK in response to Ca2+ signaling in T lymphocytes thus reveals that TCR triggering is linked to an evolutionally conserved serine kinase that regulates energy metabolism. Moreover, AMPK does not just react to cellular energy depletion but also anticipates it.

scholarly journals Energy sensing by the AMP-activated protein kinase and its effects on muscle metabolism

2010 ◽  
Vol 70 (1) ◽  
pp. 92-99 ◽  
Author(s):  
D. Grahame Hardie
Keyword(s):  
Protein Kinase ◽  
Endurance Exercise ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Whole Body ◽  
Acid Oxidation ◽  
Ampk Activation ◽  
Energy Status ◽  
Cellular Energy ◽  
Amp Activated Protein Kinase

The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status, and a regulator of energy balance at both the cellular and whole body levels. Although ubiquitously expressed, its function is best understood in skeletal muscle. AMPK contains sites that reversibly bind AMP or ATP, with an increase in cellular AMP:ATP ratio (signalling a fall in cellular energy status) switching on the kinase. In muscle, AMPK activation is therefore triggered by sustained contraction, and appears to be particularly important in the metabolic changes that occur in the transition from resistance to endurance exercise. Once activated, AMPK switches on catabolic processes that generate ATP, while switching off energy-requiring processes not essential in the short term. Thus, it acutely activates glucose uptake (by promoting translocation of the transporter GLUT4 to the membrane) and fatty acid oxidation, while switching off glycogen synthesis and protein synthesis (the later via inactivation of the mammalian target-of-rapamycin pathway). Prolonged AMPK activation also causes some of the chronic adaptations to endurance exercise, such as increased GLUT4 expression and mitochondrial biogenesis. AMPK contains a glycogen-binding domain that causes a sub-fraction to bind to the surface of the glycogen particle, and it can inhibit glycogen synthesis by phosphorylating glycogen synthase. We have shown that AMPK is inhibited by exposed non-reducing ends in glycogen. We are working on the hypothesis that this ensures that glycogen synthesis is rapidly activated when glycogen becomes depleted after exercise, but is switched off again as soon as glycogen stores are replenished.

scholarly journals 0358: Differential AMP-activated protein kinase (AMPK) activation in platelets, in response to various agonists. Comparison between human and murine platelets

2014 ◽  
Vol 6 ◽  
pp. 57
Author(s):  
Sophie Lepropre ◽  
Marie-Blanche Onselaer ◽  
Cécile Oury ◽  
Luc Bertrand ◽  
Jean-Louis Vanoverschelde ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Ampk Activation ◽  
Amp Activated Protein Kinase

AMPK activation with AICAR provokes an acute fall in plasma [K+]

2008 ◽  
Vol 294 (1) ◽  
pp. C126-C135 ◽  
Author(s):  
Dan Zheng ◽  
Anjana Perianayagam ◽  
Donna H. Lee ◽  
M. Douglas Brannan ◽  
Li E. Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Infusion Rate ◽  
Extracellular Fluid ◽  
Ampk Activation ◽  
Conscious Rats ◽  
Significant Fall ◽  
Ampk Phosphorylation ◽  
Atp Levels ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK), activated by an increase in intracellular AMP-to-ATP ratio, stimulates pathways that can restore ATP levels. We tested the hypothesis that AMPK activation influences extracellular fluid (ECF) K+ homeostasis. In conscious rats, AMPK was activated with 5-aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) infusion: 38.4 mg/kg bolus then 4 mg·kg−1·min−1 infusion. Plasma [K+] and [glucose] both dropped at 1 h of AICAR infusion and [K+] dropped to 3.3 ± 0.04 mM by 3 h, linearly related to the increase in muscle AMPK phosphorylation. AICAR treatment did not increase urinary K+ excretion. AICAR lowered [K+] whether plasma [K+] was chronically elevated or lowered. The K+ infusion rate needed to maintain baseline plasma [K+] reached 15.7 ± 1.3 μmol K+·kg−1·min−1 between 120 and 180 min AICAR infusion. In mice expressing a dominant inhibitory form of AMPK in the muscle (Tg-KD1), baseline [K+] was not different from controls (4.2 ± 0.1 mM), but the fall in plasma [K+] in response to AICAR (0.25 g/kg) was blunted: [K+] fell to 3.6 ± 0.1 in controls and to 3.9 ± 0.1 mM in Tg-KD1, suggesting that ECF K+ redistributes, at least in part, to muscle ICF. In summary, these findings illustrate that activation of AMPK activity with AICAR provokes a significant fall in plasma [K+] and suggest a novel mechanism for redistributing K+ from ECF to ICF.

scholarly journals Activation of AMPK under Hypoxia: Many Roads Leading to Rome

2020 ◽  
Vol 21 (7) ◽  
pp. 2428 ◽  
Author(s):  
Franziska Dengler
Keyword(s):  
Current Knowledge ◽  
Protective Action ◽  
Energy Levels ◽  
Hypoxia Inducible Factor ◽  
Protective Effects ◽  
Ampk Activation ◽  
Cellular Energy ◽  
Energy Sensor ◽  
Atp Supply ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is known as a pivotal cellular energy sensor, mediating the adaptation to low energy levels by deactivating anabolic processes and activating catabolic processes in order to restore the cellular ATP supply when the cellular AMP/ATP ratio is increased. Besides this well-known role, it has also been shown to exert protective effects under hypoxia. While an insufficient supply with oxygen might easily deplete cellular energy levels, i.e., ATP concentration, manifold other mechanisms have been suggested and are heavily disputed regarding the activation of AMPK under hypoxia independently from cellular AMP concentrations. However, an activation of AMPK preceding energy depletion could induce a timely adaptation reaction preventing more serious damage. A connection between AMPK and the master regulator of hypoxic adaptation via gene transcription, hypoxia-inducible factor (HIF), has also been taken into account, orchestrating their concerted protective action. This review will summarize the current knowledge on mechanisms of AMPK activation under hypoxia and its interrelationship with HIF.

scholarly journals AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

2019 ◽  
Vol 60 (5) ◽  
pp. 937-952 ◽  
Author(s):  
Anne-Emilie Declèves ◽  
Anna V. Mathew ◽  
Aaron M. Armando ◽  
Xianlin Han ◽  
Edward A. Dennis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Kidney Disease ◽  
Ampk Activation ◽  
High Fat ◽  
Kinase Activation ◽  
Venous Circulation ◽  
Protein Kinase Activation ◽  
Anti Inflammatory ◽  
Amp Activated Protein Kinase

High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMP-activated protein kinase (AMPK) activation. Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative MS to determine PUFA and eicosanoid content in kidneys, urine, and renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free pro-inflammatory arachidonic acid (AA) and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA- and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPA-derived LOX and NE metabolites decreased. Conversely, treatment with 5-aminoimidazole-4-carboxamide-1-β-D-furanosyl 5′-monophosphate (AICAR), an AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, kidney and circulating AA, AA metabolites, EPA-derived LOX, and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro- and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

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