Netrin-1 Prevents Rat Primary Cortical Neurons from Apoptosis Via the DCC/ERK Pathway

Overview

Journal Front Cell Neurosci

Specialty Cell Biology

Date 2018 Jan 12

PMID 29321724

Citations 12

Authors

Jianhao Chen

Houwei Du

Yixian Zhang

Hongbin Chen

Mouwei Zheng

Peiqiang Lin

Quan Lan

Qilin Yuan

Yongxing Lai

Xiaodong Pan

Ronghua Chen

Nan Liu

Affiliations

Soon will be listed here.

Abstract

In the nervous system, Netrin-1 serves as a neural guide, mediating the neuronal development. However, it remains blurred whether Netrin-1 can protect neurons from apoptosis induced by cerebral stroke. In the current study, the cultured rat primary cortical neurons were transfected with Netrin-1-encoding lentivirus before the oxygen-glucose-deprivation (OGD) treatment. Cell death and apoptosis were evaluated by lactate dehydrogenase (LDH) release and flow cytometry. We found that Netrin-1 attenuated OGD-induced cell death and neuronal apoptosis at 24 h after OGD treatment, and that the overexpression of Netrin-1 activated the ERK signaling pathway. These effects were partly abolished by blocking its receptor deleted in colorectal cancer (DCC) or U0126, an inhibitor of the ERK signaling pathway. Netrin-1 overexpression in neurons elevated the expression of DCC, on mRNA level and protein level. Netrin-1 also reduced DNA damage. Taken together, our findings suggest that Netrin-1 attenuates cell death and neuronal apoptosis via the DCC/ERK signaling pathway in the cultured primary cortical neurons after OGD injury, which may involve the mediation of DNA damage in the neurons.

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References

An X, Zhao Z, Luo Y, Zhang R, Tang X, Hao D . Netrin-1 suppresses the MEK/ERK pathway and ITGB4 in pancreatic cancer. Oncotarget. 2016; 7(17):24719-33. PMC: 5029736. DOI: 10.18632/oncotarget.8348. View

Ma W, Shang Y, Wei Z, Wen W, Wang W, Zhang M . Phosphorylation of DCC by ERK2 is facilitated by direct docking of the receptor P1 domain to the kinase. Structure. 2010; 18(11):1502-11. DOI: 10.1016/j.str.2010.08.011. View

Lin L, Chen H, Zhang Y, Lin W, Liu Y, Li T . IL-10 Protects Neurites in Oxygen-Glucose-Deprived Cortical Neurons through the PI3K/Akt Pathway. PLoS One. 2015; 10(9):e0136959. PMC: 4569574. DOI: 10.1371/journal.pone.0136959. View

Chitikova Z, Gordeev S, Bykova T, Zubova S, Pospelov V, Pospelova T . Sustained activation of DNA damage response in irradiated apoptosis-resistant cells induces reversible senescence associated with mTOR downregulation and expression of stem cell markers. Cell Cycle. 2014; 13(9):1424-39. PMC: 4050140. DOI: 10.4161/cc.28402. View

Wu H, Li G, Xie J, Li R, Chen Q, Chen J . Resveratrol ameliorates myocardial fibrosis by inhibiting ROS/ERK/TGF-β/periostin pathway in STZ-induced diabetic mice. BMC Cardiovasc Disord. 2016; 16:5. PMC: 4707778. DOI: 10.1186/s12872-015-0169-z. View

Dai Y, Chen S, Pei X, Almenara J, Kramer L, Venditti C . Interruption of the Ras/MEK/ERK signaling cascade enhances Chk1 inhibitor-induced DNA damage in vitro and in vivo in human multiple myeloma cells. Blood. 2008; 112(6):2439-49. PMC: 2532812. DOI: 10.1182/blood-2008-05-159392. View

Wei F, Xie Y, Tao L, Tang D . Both ERK1 and ERK2 kinases promote G2/M arrest in etoposide-treated MCF7 cells by facilitating ATM activation. Cell Signal. 2010; 22(11):1783-9. DOI: 10.1016/j.cellsig.2010.07.007. View

Tian Y, Xie Q, Tian Y, Liu Y, Huang Z, Fan C . Radioactive ¹²⁵I seed inhibits the cell growth, migration, and invasion of nasopharyngeal carcinoma by triggering DNA damage and inactivating VEGF-A/ERK signaling. PLoS One. 2013; 8(9):e74038. PMC: 3769370. DOI: 10.1371/journal.pone.0074038. View

Thiebault K, Mazelin L, Pays L, Llambi F, Joly M, Scoazec J . The netrin-1 receptors UNC5H are putative tumor suppressors controlling cell death commitment. Proc Natl Acad Sci U S A. 2003; 100(7):4173-8. PMC: 153067. DOI: 10.1073/pnas.0738063100. View

10.

Chen H, Lin W, Zhang Y, Lin L, Chen J, Zeng Y . IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway. Sci Rep. 2016; 6:30459. PMC: 4960594. DOI: 10.1038/srep30459. View

11.

Tan W, Popel A, Mac Gabhann F . Computational model of VEGFR2 pathway to ERK activation and modulation through receptor trafficking. Cell Signal. 2013; 25(12):2496-510. PMC: 3865527. DOI: 10.1016/j.cellsig.2013.08.015. View

12.

Lee S, Lee S, Yoon M, Park B . A new p53 target gene, RKIP, is essential for DNA damage-induced cellular senescence and suppression of ERK activation. Neoplasia. 2013; 15(7):727-37. PMC: 3689236. DOI: 10.1593/neo.121862. View

13.

Lewinska A, Adamczyk-Grochala J, Kwasniewicz E, Deregowska A, Wnuk M . Diosmin-induced senescence, apoptosis and autophagy in breast cancer cells of different p53 status and ERK activity. Toxicol Lett. 2016; 265:117-130. DOI: 10.1016/j.toxlet.2016.11.018. View

14.

Lin X, Yan J, Tang D . ERK kinases modulate the activation of PI3 kinase related kinases (PIKKs) in DNA damage response. Histol Histopathol. 2013; 28(12):1547-54. DOI: 10.14670/HH-28.1547. View

15.

Nakka V, Gusain A, Mehta S, Raghubir R . Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities. Mol Neurobiol. 2007; 37(1):7-38. DOI: 10.1007/s12035-007-8013-9. View

16.

Paradisi A, Mehlen P . Netrin-1, a missing link between chronic inflammation and tumor progression. Cell Cycle. 2010; 9(7):1253-62. DOI: 10.4161/cc.9.7.11072. View

17.

Delloye-Bourgeois C, Brambilla E, Coissieux M, Guenebeaud C, Pedeux R, Firlej V . Interference with netrin-1 and tumor cell death in non-small cell lung cancer. J Natl Cancer Inst. 2009; 101(4):237-47. DOI: 10.1093/jnci/djn491. View

18.

Harter P, Zinke J, Scholz A, Tichy J, Zachskorn C, Kvasnicka H . Netrin-1 expression is an independent prognostic factor for poor patient survival in brain metastases. PLoS One. 2014; 9(3):e92311. PMC: 3960244. DOI: 10.1371/journal.pone.0092311. View

19.

Fan Y, Shen F, Chen Y, Hao Q, Liu W, Su H . Overexpression of netrin-1 induces neovascularization in the adult mouse brain. J Cereb Blood Flow Metab. 2008; 28(9):1543-51. PMC: 2581494. DOI: 10.1038/jcbfm.2008.39. View

20.

Weng L, Wang G, Yao H, Yu M, Lin J . Epigallocatechin gallate inhibits the growth of salivary adenoid cystic carcinoma cells via the EGFR/Erk signal transduction pathway and the mitochondria apoptosis pathway. Neoplasma. 2017; 64(4):563-570. DOI: 10.4149/neo_2017_410. View