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Molecules 2013, 18(10), 12977-12986; doi:10.3390/molecules181012977
Article

Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells

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1,*  and 1,*
1 Department of Neurology, China-Japan Union Hospital, Jilin University, Changchun 130012, China 2 College of Nursing, Beihua University, Jilin City 132013, China 3 People's Hospital of Jilin Province, Changchun 130021, China 4 The 4th Hospital of Harbin Medical University, Harbin 150006, China
* Authors to whom correspondence should be addressed.
Received: 12 July 2013 / Revised: 10 October 2013 / Accepted: 11 October 2013 / Published: 17 October 2013
(This article belongs to the Section Medicinal Chemistry)
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Abstract

Activin A (ActA), a member of transforming growth factor-beta (TGF-b) super- family, affects many cellular processes, including ischemic stroke. Though the neuroprotective effects of exogenous ActA on oxygen-glucose deprivation (OGD) injury have already been reported by us, the endogenous role of ActA remains poorly understood. To further define the role and mechanism of endogenous ActA and its signaling in response to acute ischemic damage, we used an OGD model in PC12 cells to simulate ischemic injury on neurons in vitro. Cells were pre-treated by monoclonal antibody against activin receptor type IIA (ActRII-Ab). We found that ActRII-Ab augments ischemic injury in PC12 cells. Further, the extracellular secretion of ActA as well as phosphorylation of smad3 in PC12 cells was also up-regulated by OGD, but suppressed by ActRII-Ab. Taken together, our results show that ActRII-Ab may augment ischemic injury via blocking of transmembrane signal transduction of ActA, which confirmed the existence of endogenous neuroprotective effects derived from the ActA/Smads pathway. ActRIIA plays an important role in transferring neuronal protective signals inside. It is highly possible that ActA transmembrance signaling is a part of the positive feed-back loop for extracellular ActA secretion.
Keywords: ischemic injury; OGD; activin A; ActA/Smads pathway ischemic injury; OGD; activin A; ActA/Smads pathway
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Mang, J.; Mei, C.-L.; Wang, J.-Q.; Li, Z.-S.; Chu, T.-T.; He, J.-T.; Xu, Z.-X. Endogenous Protection Derived from Activin A/Smads Transduction Loop Stimulated via Ischemic Injury in PC12 Cells. Molecules 2013, 18, 12977-12986.

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