Title
The Brain Uncoupling Protein Ucp4 Attenuates Mitochondrial Toxin-Induced Cell Death: Role Of Extracellular Signal-Regulated Kinases In Bioenergetics Adaptation And Cell Survival
Keywords
Energy metabolism; Glycolysis; Mitochondrial uncoupling protein
Abstract
Increased bioenergetics demand can stimulate compensatory increases in glucose metabolism. We previously reported that neural cells expressing the brain uncoupling protein UCP4 exhibit enhanced dependency on glucose for support of cellular bioenergetics and survival. The switch from oxidative toward glycolytic metabolism reduces the production of toxic reactive oxygen species (ROS) and increases cellular resistance to toxicity induced by 3-nitropropionic acid, a mitochondrial complex II inhibitor that compromises cellular bioenergetics. In this study we elucidate the underlying mechanism whereby expression of UCP4 promotes bioenergetics adaptation and cell survival. We found that activation of extracellular signal-regulated kinases (ERKs) is necessary and sufficient for the increased dependency on glucose utilization. Pharmacological inhibition of ERKs not only abrogated bioenergetics adaptation but also reduced the activation of cAMP-responsive element-binding (CREB) protein suggesting that CREB protein signaling contributes in part to UCP4-dependent cell death rescue from 3-nitropropionic acid-induced toxicity. We also demonstrated that activation of ERKs by growth factors ameliorated the bioenergetics compromise and reduced cellular toxicity induced by 3-nitropropionic acid. Collectively, our results support the involvement of ERKs in UCP4 dependent bioenergetics adaptation and cell survival. © Springer Science+Business Media, LLC 2009.
Publication Date
4-8-2009
Publication Title
Neurotoxicity Research
Volume
16
Issue
1
Number of Pages
14-29
Document Type
Article
Personal Identifier
scopus
DOI Link
https://doi.org/10.1007/s12640-009-9039-8
Copyright Status
Unknown
Socpus ID
70349744001 (Scopus)
Source API URL
https://api.elsevier.com/content/abstract/scopus_id/70349744001
STARS Citation
Wei, Zelan; Chigurupati, Srinivasulu; Bagsiyao, Pamela; Henriquez, Alicia; and Chan, Sic L., "The Brain Uncoupling Protein Ucp4 Attenuates Mitochondrial Toxin-Induced Cell Death: Role Of Extracellular Signal-Regulated Kinases In Bioenergetics Adaptation And Cell Survival" (2009). Scopus Export 2000s. 11945.
https://stars.library.ucf.edu/scopus2000/11945