The effect of activin A on signal transduction pathways in PC12 cells subjected to oxygen and glucose deprivation

Guo,Hongliang; Shen,Xiaoran; Xu,Ye; He,Youdi; Hu,Wenli

doi:10.3892/ijmm.2013.1539

The effect of activin A on signal transduction pathways in PC12 cells subjected to oxygen and glucose deprivation

Authors:
- Hongliang Guo
- Xiaoran Shen
- Ye Xu
- Youdi He
- Wenli Hu
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Affiliations: Department of Neurology, Beijing Chaoyang Hospital Affiliated to Capital Medical University, Beijing 100020, P.R. China, Jilin Municipal Central Hospital, Jilin 132001, P.R. China, Medical Research Laboratory, Jilin Medical College, Jilin 132013, P.R. China
Published online on: October 30, 2013 https://doi.org/10.3892/ijmm.2013.1539
Pages: 135-141

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Abstract

The processes and mechanisms underlying brain injuries due to ischemia and anoxia have yet to be determined. Additionally, few clinical treatements are currently available. Activins have a protective role in the restoration, differentiation, and survival of injured cells, including Activin A (ActA), which acts as a neuroprotectant. However, its exact mechanism of action remains to be determined. ActA has been shown to protect neurons following ischemic brain injury. In this study, PC12 cells were differentiated into neuron-like cells after stimulation with nerve growth factor to prepare an oxygen/glucose deprivation (OGD) model in neurons. The differentiated PC12 cells, subjected to the OGD model, were exposed to ActA. Results showed that the PC12 survival rate decreased after OGD, leading to an increase in caspase-3 expression in these cells. Pretreatment with ActA was able to partially prevent OGD-induced apoptosis, likely through the downregulation of caspase-3. Futhermore, ActA pretreatment increased the expression of key proteins in the ActA/Smads signal transduction pathway, which may promote neuroprotection after OGD. Therefore, exogenous ActA may function as a neuroprotectant and provide a novel therapeutic treatment for ischemic brain injury.

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1	Massagué J: TGFbeta in cancer. Cell. 134:215–230. 2008.
2	Tretter YP, Hertel M, Munz B, ten Bruggencate G, Werner S and Alzheimer C: Induction of activin A is essential for the neuroprotective action of basic fibroblast growth factor in vivo. Nat Med. 6:812–815. 2000. View Article : Google Scholar : PubMed/NCBI
3	Lin X, Duan X, Liang YY, et al: PPM1A functions as a Smad phosphatase to terminate TGFbeta signaling. Cell. 125:915–928. 2006. View Article : Google Scholar : PubMed/NCBI
4	Ling N, Ueno N, Ying SY, et al: Inhibins and activins. Vitam Horm. 44:1–46. 1988. View Article : Google Scholar
5	Munz B, Tretter YP, Hertel M, Engelhardt F, Alzheimer C and Werner S: The roles of activins in repair processes of the skin and the brain. Mol Cell Endocrinol. 180:169–177. 2001. View Article : Google Scholar : PubMed/NCBI
6	Ageta H, Murayama A, Migishima R, et al: Activin in the brain modulates anxiety-related behavior and adult neurogenesis. PLoS One. 3:e18692008. View Article : Google Scholar : PubMed/NCBI
7	Tsuchida K, Nakatani M, Uezumi A, Murakami T and Cui X: Signal transduction pathway through activin receptors as a therapeutic target of musculoskeletal diseases and cancer. Endocr J. 55:11–21. 2008. View Article : Google Scholar : PubMed/NCBI
8	Schneyer AL, Sidis Y, Gulati A, Sun JL, Keutmann H and Krasney PA: Differential antagonism of activin, myostatin and growth and differentiation factor 11 by wild-type and mutant follistatin. Endocrinology. 149:4589–4595. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zhou WJ and Hu ZP: Expression of Smad 2 and Smad 4 proteins in brain tissue following cerebral ischemia/reperfusion in gerbils. Guoji Shenjing Bing Xue Shenjing Waike Zazhi. 35:112–114. 2008.(In Chinese).
10	Tsuchida K, Nakatani M, Hitachi K, et al: Activin signaling as an emerging target for therapeutic interventions. Cell Commun Signal. 7:152009. View Article : Google Scholar : PubMed/NCBI
11	Shoji-Kasai Y, Ageta H, Hasegawa Y, Tsuchida K, Sugino H and Inokuchi K: Activin increases the number of synaptic contacts and the length of dendritic spine necks by modulating spinal actin dynamics. J Cell Sci. 120:3830–3837. 2007. View Article : Google Scholar : PubMed/NCBI
12	Mukerji SS, Katsman EA, Wilber C, Haner NA, Selman WR and Hall AK: Activin is a neuronal survival factor that is rapidly increased after transient cerebral ischemia and hypoxia in mice. J Cereb Blood Flow Metab. 27:1161–1172. 2007. View Article : Google Scholar : PubMed/NCBI
13	Li XQ, Verge VM, Johnston JM and Zochodne DW: CGRP peptide and regenerating sensory axons. J Neuropathol Exp Neurol. 63:1092–1103. 2004.PubMed/NCBI
14	Cruise BA, Xu P and Hall AK: Wounds increase activin in skin and a vasoactive neuropeptide in sensory ganglia. Dev Biol. 271:1–10. 2004. View Article : Google Scholar : PubMed/NCBI
15	Xu P, Van Slambrouck C, Berti-Mattera L and Hall AK: Activin induces tactile allodynia and increases calcitonin gene-related peptide after peripheral inflammation. J Neurosci. 25:9227–9235. 2005. View Article : Google Scholar : PubMed/NCBI
16	Müller MR, Zheng F, Werner S and Alzheimer C: Transgenic mice expressing dominant-negative activin receptor IB in forebrain neurons reveal novel functions of activin at glutamatergic synapses. J Biol Chem. 281:29076–29084. 2006.PubMed/NCBI
17	Yasuda H, Mine T, Shibata H, et al: Activin A: an autocrine inhibitor of initiation of DNA synthesis in rat hepatocytes. J Clin Invest. 92:1491–1496. 1993. View Article : Google Scholar : PubMed/NCBI
18	Chen W, Woodruff TK and Mayo KE: Activin A induced Hep G2 liver cell apoptosis: involvement of activin receptors and smad proteins. Endocrinology. 141:1263–1272. 2000.PubMed/NCBI
19	Yuan J and Yankner BA: Apoptosis in the nervous system. Nature. 407:802–809. 2000. View Article : Google Scholar
20	Gurney ME, Tomasselli AG and Heinrikson RL: Neurobiology. Stay the executioner’s hand. Science. 288:283–284. 2000.
21	Lee JM, Grabb MC, Zipfel GJ and Choi DW: Brain tissue responses to ischemia. J Clin Invest. 106:723–731. 2000. View Article : Google Scholar : PubMed/NCBI
22	Benchoua A, Guégan C, Couriaud C, et al: Specific caspase pathways are activated in the two stages of cerebral infarction. J Neurosci. 21:7127–7134. 2001.PubMed/NCBI
23	Harrison DC, Davis RP, Bond BC, et al: Caspase mRNA expression in a rat model of focal cerebral ischemia. Brain Res Mol Brain Res. 89:133–146. 2001. View Article : Google Scholar : PubMed/NCBI
24	Guo HL, Xu ZX and Li XH: Use of RNAi silencing to target preconditioned glial cell line-derived neurotrophic factor in neuronal apoptosis. Neural Regen Res. 6:510–516. 2011.