Type

Journal Article

Authors

Jochen H M Prehn
David C Henshall
Tobias Engel
Ina Woods
Caroline T Bonner
Liam P Tuffy
Katsura Kuroki
Helena P Bonner
Manus W Ward
Caoimhín G Concannon

Subjects

Biochemistry

Topics
apoptosis animals physiopathology epilepsy mice brain tunicamycin glutamic acid puma protein mouse metabolism neurotoxins endoplasmic reticulum drug effects calcium signaling mice knockout female tumor suppressor proteins apoptosis regulatory proteins genetics rats wistar toxicity organ culture techniques neurons pathology male physiology receptors n methyl d aspartate oxidative stress brain ischemia rats nerve degeneration mice inbred c57bl

NMDA receptor-mediated excitotoxic neuronal apoptosis in vitro and in vivo occurs in an ER stress and PUMA independent manner. (2007)

Abstract Disruption of endoplasmic reticulum (ER) Ca2+ homeostasis and ER dysfunction have been suggested to contribute to excitotoxic and ischaemic neuronal injury. Previously, we have characterized the neural transcriptome following ER stress and identified the BH3-only protein, p53 up-regulated mediator of apoptosis (PUMA), as a central mediator of ER stress toxicity. In this study, we investigated the effects of excitotoxic injury on ER Ca2+ levels and induction of ER stress responses in models of glutamate- and NMDA-induced excitotoxic apoptosis. While exposure to the ER stressor tunicamycin induced an ER stress response in cerebellar granule neurons, transcriptional activation of targets of the ER stress response, including PUMA, were absent following glutamate-induced apoptosis. Confocal imaging revealed no long-term changes in the ER Ca2+ level in response to glutamate. Murine cortical neurons and organotypic hippocampal slice cultures from PUMA+/+ and PUMA-/- animals provided no evidence of ER stress and did not differ in their sensitivity to NMDA. Finally, NMDA-induced excitotoxic apoptosis in vivo was not associated with ER stress, nor did deficiency in PUMA alleviate the injury induced. Our data suggest that NMDA receptor-mediated excitotoxic apoptosis occurs in vitro and in vivo in an ER stress and PUMA independent manner.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, David C Henshall, Tobias Engel, Ina Woods, Caroline T Bonner, Liam P Tuffy, Katsura Kuroki, Helena P Bonner, Manus W Ward, Caoimhín G Concannon

Experts in our system

1
Jochen H M Prehn
Royal College of Surgeons in Ireland
Total Publications: 206
 
2
David C Henshall
Royal College of Surgeons in Ireland
Total Publications: 127
 
3
Tobias Engel
Royal College of Surgeons in Ireland
Total Publications: 66
 
4
Ina Woods
Royal College of Surgeons in Ireland
Total Publications: 16
 
5
Liam P Tuffy
Royal College of Surgeons in Ireland
Total Publications: 13
 
6
Helena P Bonner
Royal College of Surgeons in Ireland
Total Publications: 15
 
7
Caoimhín G Concannon
Royal College of Surgeons in Ireland
Total Publications: 46