Type

Journal Article

Authors

Jochen H M Prehn
David C Henshall
Guillermo Velasco
Claire M Mooney
Eva M Jimenez-Mateos
David Davila

Subjects

Biochemistry

Topics
cell death death rna binding proteins oxidative stress novel the hydrogen peroxide heat shock protein signaling pathways

Hsp27 binding to the 3'UTR of bim mRNA prevents neuronal death during oxidative stress-induced injury: a novel cytoprotective mechanism. (2014)

Abstract Neurons face a changeable microenvironment and therefore need mechanisms that allow rapid switch on/off of their cytoprotective and apoptosis-inducing signaling pathways. Cellular mechanisms that control apoptosis activation include the regulation of pro/antiapoptotic mRNAs through their 3'-untranslated region (UTR). This region holds binding elements for RNA-binding proteins, which can control mRNA translation. Here we demonstrate that heat shock protein 27 (Hsp27) prevents oxidative stress-induced cell death in cerebellar granule neurons by specific regulation of the mRNA for the proapoptotic BH3-only protein, Bim. Hsp27 depletion induced by oxidative stress using hydrogen peroxide (H2O2) correlated with bim gene activation and subsequent neuronal death, whereas enhanced Hsp27 expression prevented these. This effect could not be explained by proteasomal degradation of Bim or bim promoter inhibition; however, it was associated with a specific increase in the levels of bim mRNA and with its binding to Hsp27. Finally, we determined that enhanced Hsp27 expression in neurons exposed to H2O2 or glutamate prevented the translation of a reporter plasmid where bim-3'UTR mRNA sequence was cloned downstream of a luciferase gene. These results suggest that repression of bim mRNA translation through binding to the 3'UTR constitutes a novel cytoprotective mechanism of Hsp27 during stress in neurons.
Collections Ireland -> Royal College of Surgeons in Ireland -> PubMed

Full list of authors on original publication

Jochen H M Prehn, David C Henshall, Guillermo Velasco, Claire M Mooney, Eva M Jimenez-Mateos, David Davila

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
Claire Mooney
Royal College of Surgeons in Ireland
Total Publications: 8
 
4
Eva M Jimenez-Mateos
Royal College of Surgeons in Ireland
Total Publications: 55