1. Noncanonical Activin A Signaling in PC12 Cells: A Self-Limiting Feedback Loop
- Author
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Yang Cui, Jiaoqi Wang, Zhongxin Xu, Wei Shi, Yue Wang, Jinting He, Yankun Shao, Long-Xing Xue, Qiu-Ye Ji, Hongyu Liu, Wenzhao Liang, and Jing Mang
- 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 - 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.
- Published
- 2015