Type

Other / n/a

Authors

Jochen HM Prehn
Hans Georg König
Caoimhín G Concannon
Heiko Düssmann
Petronela Weisova
Ujval Anilkumar

Subjects

Biochemistry

Topics
stress protein kinases stress physiological hypoglycemic agents flow cytometry ribonucleotides physiological neurons n methylaspartate physics microscopy confocal adaptation microscopy myeloid cell leukemia sequence 1 protein proto oncogene proteins c bcl 2 physiology aminoimidazole carboxamide adaptation physiological animals blotting western blotting western confocal cerebral cortex mice

AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1. (2013)

Abstract Neuronal preconditioning is a phenomenon where a previous exposure to a sub-lethal stress stimulus increases the resistance of neurons towards a second, normally lethal stress stimulus. Activation of the energy stress sensor, AMP-activated protein kinase (AMPK) has been shown to contribute to the protective effects of ischaemic and mitochondrial uncoupling-induced preconditioning in neurons, however, the molecular basis of AMPK-mediated preconditioning has been less well characterized. We investigated the effect of AMPK preconditioning using 5-aminoimidazole-4-carboxamide riboside (AICAR) in a model of NMDA-mediated excitotoxic injury in primary mouse cortical neurons. Activation of AMPK with low concentrations of AICAR (0.1 mM for 2 h) induced a transient increase in AMPK phosphorylation, protecting neurons against NMDA-induced excitotoxicity. Analysing potential targets of AMPK activation, demonstrated a marked increase in mRNA expression and protein levels of the anti-apoptotic BCL-2 family protein myeloid cell leukaemia sequence 1 (MCL-1) in AICAR-preconditioned neurons. Interestingly, over-expression of MCL-1 protected neurons against NMDA-induced excitotoxicity while MCL-1 gene silencing abolished the effect of AICAR preconditioning. Monitored intracellular Ca²⁺ levels during NMDA excitation revealed that MCL-1 over-expressing neurons exhibited improved bioenergetics and markedly reduced Ca²⁺ elevations, suggesting a potential mechanism through which MCL-1 confers neuroprotection. This study identifies MCL-1 as a key effector of AMPK-induced preconditioning in neurons.
Collections Ireland -> Royal College of Surgeons in Ireland -> Physiology and Medical Physics Articles
Ireland -> Royal College of Surgeons in Ireland -> Department of Physiology and Medical Physics

Full list of authors on original publication

Jochen HM Prehn, Hans Georg König, Caoimhín G Concannon, Heiko Düssmann, Petronela Weisova, Ujval Anilkumar

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Hans Georg König
Royal College of Surgeons in Ireland
Total Publications: 22
 
3
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
4
Heiko Düssmann
Royal College of Surgeons in Ireland
Total Publications: 45
 
5
Petronela Weisova
Royal College of Surgeons in Ireland
Total Publications: 10
 
6
Ujval Anilkumar
Royal College of Surgeons in Ireland
Total Publications: 14