Type

Journal Article

Authors

Manus W Ward
Jochen H M Prehn
Caoimhín G Concannon
Caitriona Ryan
Ujval Anilkumar
Petronela Weisova

Subjects

Biochemistry

Topics
protein kinase neuronal activity reactive oxygen species energy metabolism excitotoxicity ampk mitochondrial activity protection

'Mild mitochondrial uncoupling' induced protection against neuronal excitotoxicity requires AMPK activity. (2011)

Abstract The preconditioning response conferred by a mild uncoupling of the mitochondrial membrane potential (Δψ(m)) has been attributed to altered reactive oxygen species (ROS) production and mitochondrial Ca(2+) uptake within the cells. Here we have explored if altered cellular energetics in response to a mild mitochondrial uncoupling stimulus may also contribute to the protection. The addition of 100nM FCCP for 30min to cerebellar granule neurons (CGNs) induced a transient depolarization of the Δψ(m), that was sufficient to significantly reduce CGN vulnerability to the excitotoxic stimulus, glutamate. On investigation, the mild mitochondrial 'uncoupling' stimulus resulted in a significant increase in the plasma membrane levels of the glucose transporter isoform 3, with a hyperpolarisation of Δψ(m) and increased cellular ATP levels also evident following the washout of FCCP. Furthermore, the phosphorylation state of AMP-activated protein kinase (AMPK) (Thr 172) was increased within 5min of the uncoupling stimulus and elevated up to 1h after washout. Significantly, the physiological changes and protection evident after the mild uncoupling stimulus were lost in CGNs when AMPK activity was inhibited. This study identifies an additional mechanism through which protection is mediated upon mild mitochondrial uncoupling: it implicates increased AMPK signalling and an adaptive shift in energy metabolism as mediators of the preconditioning response associated with FCCP-induced mild mitochondrial uncoupling.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Manus W Ward, Jochen H M Prehn, Caoimhín G Concannon, Caitriona Ryan, Ujval Anilkumar, Petronela Weisova

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46
 
3
Ujval Anilkumar
Royal College of Surgeons in Ireland
Total Publications: 14
 
4
Petronela Weisova
Royal College of Surgeons in Ireland
Total Publications: 10