Type

Journal Article

Authors

Jochen H M Prehn
Manus W Ward
Andreas Strasser
Marc C Devocelle
Caroline Bonner
David Davila
Helena P Bonner
Petronela Weisova
Liam P Tuffy
Caoimhín G Concannon

Subjects

Biochemistry

Topics
membrane proteins cell death metabolism bcl 2 like protein 11 animals proto oncogene proteins rats adenylate kinase genetics apoptosis apoptosis regulatory proteins microscopy confocal mice transgenic neurons mice cells cultured

AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis. (2010)

Abstract Excitotoxicity after glutamate receptor overactivation induces disturbances in cellular ion gradients, resulting in necrosis or apoptosis. Excitotoxic necrosis is triggered by rapid, irreversible ATP depletion, whereas the ability to recover cellular bioenergetics is suggested to be necessary for the activation of excitotoxic apoptosis. In this study, we demonstrate that even a transient decrease in cellular bioenergetics and an associated activation of adenosine monophosphate-activated protein kinase (AMPK) is necessary for the activation of excitotoxic apoptosis. We show that the Bcl-2 homology domain 3 (BH3)-only protein Bim, a proapoptotic Bcl-2 family member, is activated in multiple excitotoxicity paradigms, mediates excitotoxic apoptosis, and inhibits delayed Ca(2+) deregulation, mitochondrial depolarization, and apoptosis-inducing factor translocation. We demonstrate that bim activation required the activation of AMPK and that prolonged AMPK activation is sufficient to induce bim gene expression and to trigger a bim-dependent cell death. Collectively, our data demonstrate that AMPK activation and the BH3-only protein Bim couple transient energy depletion to stress-induced neuronal apoptosis.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, Manus W Ward, Andreas Strasser, Marc C Devocelle, Caroline Bonner, David Davila, Helena P Bonner, Petronela Weisova, Liam P Tuffy, Caoimhín G Concannon

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Andreas Strasser
Royal College of Surgeons in Ireland
Total Publications: 7
 
3
Marc Devocelle
Royal College of Surgeons in Ireland
Total Publications: 65
 
4
Helena P Bonner
Royal College of Surgeons in Ireland
Total Publications: 15
 
5
Petronela Weisova
Royal College of Surgeons in Ireland
Total Publications: 10
 
6
Liam P Tuffy
Royal College of Surgeons in Ireland
Total Publications: 13
 
7
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46