Royal College of Surgeons in Ireland
AMP-activated protein kinase (AMPK)-induced preconditioning in pr.pdf (5.73 MB)

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

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Version 2 2022-03-25, 14:44
Version 1 2019-11-22, 16:59
journal contribution
posted on 2022-03-25, 14:44 authored by Ujval Anilkumar, Petronela Weisová, Heiko Düssmann, Caoimhín G. Concannon, Hans-Georg König, Jochen PrehnJochen Prehn

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.



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Published Citation

Abilkumar U, Weisová P, Düssmann H, Concannon CG, König HG, Prehn JHM. AMP-activated protein kinase (AMPK)-induced preconditioning in primary cortical neurons involves activation of MCL-1. Journal of Neurochemistry. 2013;124(5):721-34.

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  • Clinical Neurological Sciences
  • Physiology and Medical Physics