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Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop
- Source :
- Neurochemical Research. 41:1073-1084
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Activin A (Act A), a member of transforming growth factor-β superfamily, plays a neuroprotective role in multiple neurological diseases through Act A/Smads signal activation. Traditionally, the up-regulation of Act A gene and extracellular Act A accumulation show the signal activation as a linear pathway. However, one of our discoveries indicated that Act A could lead a loop signaling in ischemic injury. To clarify the characteristic of this loop signaling in a non-pathological state, we up-regulated the expression of Act A, monitored extracellular Act A accumulation and examined the activity of Act A signaling, which was quantified by the expression of phosphorylated Smad3 and the fluorescence intensity of Smad4 in nuclei. The results demonstrated a noncanonical Act A signal loop with self-amplifying property in PC12 cells. Further, it showed self-limiting behavior due to temporary activation and spontaneous attenuation. This periodic behavior of Act A signal loop was found to be regulated by the level of Smad anchor for receptor activation (SARA). Moreover, increased activity of Act A signal loop could promote PC12 cell proliferation and enhance the survival rate of cells to Oxygen-Glucose Deprivation. These practical discoveries will bring new insight on the functional outcome of Act A signaling in neurological diseases by the further understanding: loop signaling.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Cell Survival
SMAD
Biology
PC12 Cells
Biochemistry
Neuroprotection
Feedback
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
Internal medicine
medicine
Extracellular
Animals
Smad3 Protein
Phosphorylation
Gene
Adaptor Proteins, Signal Transducing
Cell Proliferation
Inhibin-beta Subunits
Smad4 Protein
Cell growth
General Medicine
Feedback loop
Recombinant Proteins
Rats
Cell biology
Oxygen
Glucose
030104 developmental biology
Endocrinology
030217 neurology & neurosurgery
Signal Transduction
Transforming growth factor
Subjects
Details
- ISSN :
- 15736903 and 03643190
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Neurochemical Research
- Accession number :
- edsair.doi.dedup.....df32d0650a0e142721be66ce9a175f28