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

Dávila D, Jiménez-Mateos EM, Mooney CM, Velasco G, Henshall DC, Prehn JH - Mol. Biol. Cell (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Medical Physics and RCSI Centre for the Study of Neurological Disorders, Royal College of Surgeons in Ireland, Dublin 2, Ireland Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain daviddav@ucm.es prehn@rcsi.ie.

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Hsp27 posttranscriptionally regulates Bim levels during neuronal death induced by oxidative stress. H2O2 treatment induces Bim transcription and neuronal death by the modulation of redox-sensitive pathways such as AKT and JNKs, which leads to the activation of transcription factors that regulate the bim promoter such as FOXO3. H2O2 also reduces the levels of the antiapoptotic protein Hsp27. Up-regulation of Hsp27 levels during oxidative stress does not affect bim mRNA transcription or processing; however, it represses its translation by modulation of its 3′UTR. This mechanism contributes a novel mechanism for the neuroprotective activity of Hsp27.
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Figure 6: Hsp27 posttranscriptionally regulates Bim levels during neuronal death induced by oxidative stress. H2O2 treatment induces Bim transcription and neuronal death by the modulation of redox-sensitive pathways such as AKT and JNKs, which leads to the activation of transcription factors that regulate the bim promoter such as FOXO3. H2O2 also reduces the levels of the antiapoptotic protein Hsp27. Up-regulation of Hsp27 levels during oxidative stress does not affect bim mRNA transcription or processing; however, it represses its translation by modulation of its 3′UTR. This mechanism contributes a novel mechanism for the neuroprotective activity of Hsp27.

Mentions: In conclusion, our study describes a new role for Hsp27 levels in the posttranscriptional regulation of Bim during neuronal death induced by oxidative stress (summarized in Figure 6). This involves repression of bim translation by Hsp27 binding to the bim-3′UTR. This mechanism contributes a novel mechanism explaining the neuroprotective activity of Hsp27 and may provide novel therapeutic approaches to prevent neuronal death in diverse neurodegenerative conditions.


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

Dávila D, Jiménez-Mateos EM, Mooney CM, Velasco G, Henshall DC, Prehn JH - Mol. Biol. Cell (2014)

Hsp27 posttranscriptionally regulates Bim levels during neuronal death induced by oxidative stress. H2O2 treatment induces Bim transcription and neuronal death by the modulation of redox-sensitive pathways such as AKT and JNKs, which leads to the activation of transcription factors that regulate the bim promoter such as FOXO3. H2O2 also reduces the levels of the antiapoptotic protein Hsp27. Up-regulation of Hsp27 levels during oxidative stress does not affect bim mRNA transcription or processing; however, it represses its translation by modulation of its 3′UTR. This mechanism contributes a novel mechanism for the neuroprotective activity of Hsp27.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4214787&req=5

Figure 6: Hsp27 posttranscriptionally regulates Bim levels during neuronal death induced by oxidative stress. H2O2 treatment induces Bim transcription and neuronal death by the modulation of redox-sensitive pathways such as AKT and JNKs, which leads to the activation of transcription factors that regulate the bim promoter such as FOXO3. H2O2 also reduces the levels of the antiapoptotic protein Hsp27. Up-regulation of Hsp27 levels during oxidative stress does not affect bim mRNA transcription or processing; however, it represses its translation by modulation of its 3′UTR. This mechanism contributes a novel mechanism for the neuroprotective activity of Hsp27.
Mentions: In conclusion, our study describes a new role for Hsp27 levels in the posttranscriptional regulation of Bim during neuronal death induced by oxidative stress (summarized in Figure 6). This involves repression of bim translation by Hsp27 binding to the bim-3′UTR. This mechanism contributes a novel mechanism explaining the neuroprotective activity of Hsp27 and may provide novel therapeutic approaches to prevent neuronal death in diverse neurodegenerative conditions.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology and Medical Physics and RCSI Centre for the Study of Neurological Disorders, Royal College of Surgeons in Ireland, Dublin 2, Ireland Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain daviddav@ucm.es prehn@rcsi.ie.

Show MeSH
Related in: MedlinePlus