Type

Other / n/a

Authors

Jochen HM Prehn
C Muñoz-Pinedo
J Galindo-Moreno
S Ramírez-Peinado
Gang Chen
Ujval Anilkumar
Shona Pfeiffer

Subjects

Biochemistry

Topics
humans neurons cytology metabolism oxygen metabolism signal transducing genetics metabolism physiology brain ischemia genetics metabolism physiopathology female apoptosis animals physics mice proto oncogene proteins adaptor proteins cells cultured mice inbred c57bl male glucose metabolism

Analysis of BH3-only proteins upregulated in response to oxygen/glucose deprivation in cortical neurons identifies Bmf but not Noxa as potential mediator of neuronal injury. (2014)

Abstract Stress signaling in response to oxygen/glucose deprivation (OGD) and ischemic injury activates a group of pro-apoptotic genes, the Bcl-2 homology domain 3 (BH3)-only proteins, which are capable of activating the mitochondrial apoptosis pathway. Targeted studies previously identified the BH3-only proteins Puma, Bim and Bid to have a role in ischemic/hypoxic neuronal injury. We here investigated the transcriptional activation of pro-apoptotic BH3-only proteins after OGD-induced injury in murine neocortical neurons. We observed a potent and early upregulation of noxa at mRNA and protein level, and a significant increase in Bmf protein levels during OGD in neocortical neurons and in the ipsilateral cortex of mice subjected to transient middle cerebral artery occlusion (tMCAO). Surprisingly, gene deficiency in noxa reduced neither OGD- nor glutamate-induced neuronal injury in cortical neurons and failed to influence infarct size or neurological deficits after tMCAO. In contrast, bmf deficiency induced significant protection against OGD- or glutamate-induced injury in cultured neurons, and bmf-deficient mice showed reduced neurological deficits after tMCAO in vivo. Collectively, our data not only point to a role of Bmf as a BH3-only protein contributing to excitotoxic and ischemic neuronal injury but also demonstrate that the early and potent induction of noxa does not influence ischemic neuronal injury.
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, C Muñoz-Pinedo, J Galindo-Moreno, S Ramírez-Peinado, Gang Chen, Ujval Anilkumar, Shona Pfeiffer

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
G Chen
Royal College of Surgeons in Ireland
Total Publications: 19
 
3
Ujval Anilkumar
Royal College of Surgeons in Ireland
Total Publications: 14
 
4
Shona Pfeiffer
Royal College of Surgeons in Ireland
Total Publications: 14