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Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop.
- Source :
- Neurochemical Research; May2016, Vol. 41 Issue 5, p1073-1084, 12p
- Publication Year :
- 2016
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03643190
- Volume :
- 41
- Issue :
- 5
- Database :
- Complementary Index
- Journal :
- Neurochemical Research
- Publication Type :
- Academic Journal
- Accession number :
- 114603260
- Full Text :
- https://doi.org/10.1007/s11064-015-1797-5