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Mature Neurons Dynamically Restrict Apoptosis via Redundant Pre-Mitochondrial Brakes
Mature Neurons Dynamically Restrict Apoptosis via Redundant Pre-Mitochondrial Brakes
- Publication Year :
- 2016
-
Abstract
- Apoptotic cell death is critical for the early development of the nervous system, but once the nervous system is established, the apoptotic pathway becomes highly restricted in mature neurons. However, the mechanisms underlying this increased resistance to apoptosis in these mature neurons are not completely understood. We have previously found that members of the miR-29 family of microRNAs (miRNAs) are induced with neuronal maturation and that overexpression of miR-29 was sufficient to restrict apoptosis in neurons. To determine whether endogenous miR-29 alone was responsible for the inhibition of cytochrome c release in mature neurons, we examined the status of the apoptotic pathway in sympathetic neurons deficient for all three miR-29 family members. Unexpectedly, we found that the apoptotic pathway remained largely restricted in miR-29-deficient mature neurons. We therefore probed for additional mechanisms by which mature neurons resist apoptosis. We identify miR-24 as another miRNA that is upregulated in the maturing cerebellum and sympathetic neurons that can act redundantly with miR-29 by targeting a similar repertoire of prodeath BH3-only genes. Overall, our results reveal that mature neurons engage multiple redundant brakes to restrict the apoptotic pathway and ensure their long-term survival.
- Subjects :
- 0301 basic medicine
Nervous system
Cerebellum
Endogeny
Apoptosis
Biochemistry
Article
03 medical and health sciences
Gene Knockout Techniques
Mice
Downregulation and upregulation
Proto-Oncogene Proteins
microRNA
medicine
Animals
Humans
Molecular Biology
Gene
3' Untranslated Regions
Cells, Cultured
Neurons
Microscopy, Video
biology
Bcl-2-Like Protein 11
Reverse Transcriptase Polymerase Chain Reaction
Cytochrome c
Tumor Suppressor Proteins
Cytochromes c
Cell Biology
Cell biology
Mitochondria
MicroRNAs
030104 developmental biology
medicine.anatomical_structure
HEK293 Cells
nervous system
Animals, Newborn
Gene Expression Regulation
Microscopy, Fluorescence
biology.protein
Ganglia
Apoptosis Regulatory Proteins
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....beac169e9ddcd03c754d0c6fcd7a307b