scholarly journals AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1

2012 ◽  
Vol 124 (5) ◽  
pp. 721-734 ◽  
Author(s):  
Ujval Anilkumar ◽  
Petronela Weisová ◽  
Heiko Düssmann ◽  
Caoimhín G. Concannon ◽  
Hans-Georg König ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cortical Neurons ◽  
Primary Cortical Neurons ◽  
Amp Activated Protein Kinase

AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid β-peptide exposure

2011 ◽  
Vol 434 (3) ◽  
pp. 503-512 ◽  
Author(s):  
Claire Thornton ◽  
Nicola J. Bright ◽  
Magdalena Sastre ◽  
Phillip J. Muckett ◽  
David Carling
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Protein Kinase ◽  
Cortical Neurons ◽  
Amyloid Β ◽  
Amyloid Β Peptide ◽  
Aβ Amyloid ◽  
Primary Mouse ◽  
Cellular Stresses ◽  
Amp Activated Protein Kinase

Hyperphosphorylation of tau is a hallmark of Alzheimer's disease and other tauopathies. Although the mechanisms underlying hyperphosphorylation are not fully understood, cellular stresses such as impaired energy metabolism are thought to influence the signalling cascade. The AMPK (AMP-activated protein kinase)-related kinases MARK (microtubule-associated protein-regulating kinase/microtubule affinity-regulating kinase) and BRSK (brain-specific kinase) have been implicated in tau phosphorylation, but are insensitive to activation by cellular stress. In the present study, we show that AMPK itself phosphorylates tau on a number of sites, including Ser262 and Ser396, altering microtubule binding of tau. In primary mouse cortical neurons, CaMKKβ (Ca2+/calmodulin-dependent protein kinase kinase β) activation of AMPK in response to Aβ (amyloid-β peptide)-(1–42) leads to increased phosphorylation of tau at Ser262/Ser356 and Ser396. Activation of AMPK by Aβ-(1–42) is inhibited by memantine, a partial antagonist of the NMDA (N-methyl-D-aspartate) receptor and currently licensed for the treatment of Alzheimer's disease. These findings identify a pathway in which Aβ-(1–42) activates CaMKKβ and AMPK via the NMDA receptor, suggesting the possibility that AMPK plays a role in the pathophysiological phosphorylation of tau.

Comparison of the Changes in Protein Kinase C Induced by Glutamate in Primary Cortical Neurons and by in Vivo Cerebral Ischaemia

1998 ◽  
Vol 10 (4) ◽  
pp. 291-295 ◽  
Author(s):  
Balu R Chakravarthy ◽  
Jian Wang ◽  
Roger Tremblay ◽  
Trevor G Atkinson ◽  
Fuhu Wang ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cerebral Ischaemia ◽  
Cortical Neurons ◽  
Primary Cortical Neurons ◽  
Kinase C

scholarly journals Metabolic oxidative stress elicited by the copper(II) complex [Cu(isaepy)2] triggers apoptosis in SH-SY5Y cells through the induction of the AMP-activated protein kinase/p38MAPK/p53 signalling axis: evidence for a combined use with 3-bromopyruvate in neuroblastoma treatment

2011 ◽  
Vol 437 (3) ◽  
pp. 443-453 ◽  
Author(s):  
Giuseppe Filomeni ◽  
Simone Cardaci ◽  
Ana Maria Da Costa Ferreira ◽  
Giuseppe Rotilio ◽  
Maria Rosa Ciriolo
Keyword(s):  
Protein Kinase ◽  
Cortical Neurons ◽  
Reverse Genetics ◽  
Combined Treatment ◽  
Pentose Phosphate ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Negative Mutant ◽  
Induced Apoptosis ◽  
Amp Activated Protein Kinase

We have demonstrated previously that the complex bis[(2-oxindol-3-ylimino)-2-(2-aminoethyl)pyridine-N,N′]copper(II), named [Cu(isaepy)2], induces AMPK (AMP-activated protein kinase)-dependent/p53-mediated apoptosis in tumour cells by targeting mitochondria. In the present study, we found that p38MAPK (p38 mitogen-activated protein kinase) is the molecular link in the phosphorylation cascade connecting AMPK to p53. Transfection of SH-SY5Y cells with a dominant-negative mutant of AMPK resulted in a decrease in apoptosis and a significant reduction in phospho-active p38MAPK and p53. Similarly, reverse genetics of p38MAPK yielded a reduction in p53 and a decrease in the extent of apoptosis, confirming an exclusive hierarchy of activation that proceeds via AMPK/p38MAPK/p53. Fuel supplies counteracted [Cu(isaepy)2]-induced apoptosis and AMPK/p38MAPK/p53 activation, with glucose being the most effective, suggesting a role for energetic imbalance in [Cu(isaepy)2] toxicity. Co-administration of 3BrPA (3-bromopyruvate), a well-known inhibitor of glycolysis, and succinate dehydrogenase, enhanced apoptosis and AMPK/p38MAPK/p53 signalling pathway activation. Under these conditions, no toxic effect was observed in SOD (superoxide dismutase)-overexpressing SH-SY5Y cells or in PCNs (primary cortical neurons), which are, conversely, sensitized to the combined treatment with [Cu(isaepy)2] and 3BrPA only if grown in low-glucose medium or incubated with the glucose-6-phosphate dehydrogenase inhibitor dehydroepiandrosterone. Overall, the results suggest that NADPH deriving from the pentose phosphate pathway contributes to PCN resistance to [Cu(isaepy)2] toxicity and propose its employment in combination with 3BrPA as possible tool for cancer treatment.

Chronic activation of AMP-activated protein kinase increases monocarboxylate transporter 2 and 4 expression in skeletal muscle

2017 ◽  
Vol 95 (8) ◽  
pp. 3552
Author(s):  
E. M. England ◽  
H. Shi ◽  
S. K. Matarneh ◽  
E. M. Oliver ◽  
E. T. Helm ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Monocarboxylate Transporter ◽  
Chronic Activation ◽  
Amp Activated Protein Kinase
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