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Changqin NO. 1 inhibits neuronal apoptosis via suppressing GAS5 expression in a traumatic brain injury mice model

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Published/Copyright: January 17, 2019

Abstract

The present study was designed to investigate the mechanism of the traditional Chinese medicine Changqin NO. 1 on the amelioration of traumatic brain injury (TBI). Adult male C57BL/6J mice and newborn mice were used to generate a mouse TBI model and harvest primary neurons, respectively. The localizations of specific neural markers neuropilin-1 (Nrp-1), growth-associated protein-43 (GAP-43) and microtubule-associated protein Tau (Tau) were examined in brain tissues by immunohistochemistry. Terminal deoxynucleotidyl transferase dUTP nick end labeling apoptotic cell detection in tissue sections and the CCK-8 cell viability assay were performed to examine neuronal apoptosis. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were also carried out in this study. The association between long non-coding RNA (lncRNA) growth-arrest specific 5 (GAS5), miR-335 and RAS p21 GTPase activating protein 1 (Rasa1) was disclosed using the dual-luciferase reporter assay. Changqin NO. 1 inhibited TBI-induced neuronal apoptosis in vivo and in vitro. GAS5 functioned as a competing endogenous RNA (ceRNA) by sponging miR-335 to upregulate Rasa1 expression in mouse neuronal cells. Further investigations demonstrated that GAS5 promoted neuronal apoptosis following TBI via the miR-335/Rasa1 axis. In vivo experiments indicated that Changqin NO. 1 exerted neuroprotection during TBI via the GAS5/miR-335/Rasa1 axis. Changqin NO. 1 promoted neuroprotective effects by inhibiting neuronal apoptosis via the GAS5/miR-335/Rasa1 axis in TBI.

References

Chen, L.L. and Zhao, J.C. (2014). Functional analysis of long noncoding RNAs in development and disease. Adv. Exp. Med. Biol. 825, 129–158.10.1007/978-1-4939-1221-6_4Search in Google Scholar PubMed

Chen, Y.Y., Wang, D.S., Zhu, H.B., Xia, X.U., and Dai, X.P. (2017).Clinical study on Changqin No. 1 combined with Western therapy in treating severe traumatic brain injury. Chin. J. Inform. Trd. Chin. Med. 24, 17–21.Search in Google Scholar

Coupland, K.G., Kim, W.S., Halliday, G.M., Hallupp, M., Dobson-Stone, C., and Kwok, J.B. (2016). Role of the long non-coding RNA MAPT-AS1 in regulation of microtubule associated protein Tau (MAPT) expression in Parkinson’s disease. PLoS One 11, e0157924.10.1371/journal.pone.0157924Search in Google Scholar PubMed PubMed Central

Dong, H., Gao, Z., Rong, H., Jin, M., and Zhang, X. (2014). β-asarone reverses chronic unpredictable mild stress-induced depression-like behavior and promotes hippocampal neurogenesis in rats. Molecules 19, 5634–5649.10.3390/molecules19055634Search in Google Scholar PubMed PubMed Central

Hancock, M.L., Preitner, N., Quan, J., and Flanagan, J.G. (2014). MicroRNA-132 is enriched in developing axons, locally regulates Rasa1 mRNA, and promotes axon extension. J. Neurosci. 34, 66–78.10.1523/JNEUROSCI.3371-13.2014Search in Google Scholar PubMed PubMed Central

Hao, N.B., He, Y.F., Li, X.Q., Wang, K., and Wang, R.L. (2017). The role of miRNA and lncRNA in gastric cancer. Oncotarget 8, 81572.10.18632/oncotarget.19197Search in Google Scholar PubMed PubMed Central

Hsieh, T.H., Kang, J.W., Lai, J.H., Huang, Y.Z., Rotenberg, A., Chen, K.Y., Wang, J.Y., Chan, S.Y., Chen, S.C., and Chiang, Y.H. (2017). Relationship of mechanical impact magnitude to neurologic dysfunction severity in a rat traumatic brain injury model. PLoS One 12, e0178186.10.1371/journal.pone.0178186Search in Google Scholar PubMed PubMed Central

Huang, L., Deng, M., He, Y., and Fang, Y. (2015). β-asarone and levodopa co-administration protects against 6-hydroxydopamine-induced damage in parkinsonian rat mesencephalon by regulating autophagy: down-expression Beclin-1 and light chain 3B and up-expression P62. Clin. Exp. Pharmacol. Physiol. 42, 269–277.10.1111/1440-1681.12344Search in Google Scholar PubMed

Huang, L., Deng, M., He, Y., Lu, S., Liu, S., and Fang, Y. (2016). β-asarone increases MEF2D and TH levels and reduces α-synuclein level in 6-OHDA-induced rats via regulating the HSP70/MAPK/MEF2D/Beclin-1 pathway: Chaperone-mediated autophagy activation, macroautophagy inhibition and HSP70 up-expression. Behav. Brain Res. 313, 370–379.10.1016/j.bbr.2016.07.028Search in Google Scholar PubMed

Lapinski, P.E., Kwon, S., Lubeck, B.A., Wilkinson, J.E., Srinivasan, R.S., Sevickmuraca, E., and King, P.D. (2012). RASA1 maintains the lymphatic vasculature in a quiescent functional state in mice. J. Clin. Invest. 122, 733–747.10.1172/JCI46116Search in Google Scholar PubMed PubMed Central

Liu, Z.F., Liang, Z.Q., Li, L., Zhou, Y.B., Wang, Z.B., Gu, W.F., Tu, L.Y., and Zhao, J. (2016). MiR-335 functions as a tumor suppressor and regulates survivin expression in osteosarcoma. Eur. Rev. Med. Pharmacol. Sci. 20, 1251–1257.Search in Google Scholar

Liu, H., Lai, X., Xu, Y., Miao, J., Li, C., Liu, J., Hua, Y., Ma, Q., and Chen, Q. (2017). α-Asarone attenuates cognitive deficit in a pilocarpine-induced status epilepticus rat model a decrease in the nuclear factor-κB activation and reduction in microglia neuroinflammation. Front Neurol. 8, 661.10.3389/fneur.2017.00661Search in Google Scholar PubMed PubMed Central

Ning, B., Deng, M., Zhang, Q., Wang, N., and Fang, Y. (2016). β-Asarone inhibits IRE1/XBP1 endoplasmic reticulum stress pathway in 6-OHDA-induced Parkinsonian rats. Neurochem. Res. 41, 2097–2101.10.1007/s11064-016-1922-0Search in Google Scholar PubMed

Santoro, M., Nociti, V., Lucchini, M., De Fino, C., Losavio, F.A., and Mirabella, M. (2016). Expression profile of long non-coding RNAs in serum of patients with multiple sclerosis. J. Mol. Neurosci. 59, 18–23.10.1007/s12031-016-0741-8Search in Google Scholar PubMed

Surgucheva, I., He, S., Rich, M.C., Sharma, R., Ninkina, N.N., Stahel, P.F., and Surguchov, A. (2014). Role of synucleins in traumatic brain injury – an experimental in vitro and in vivo study in mice. Mol. Cellular Neurosci. 63, 114–123.10.1016/j.mcn.2014.10.005Search in Google Scholar PubMed

Tsai, P.C. (2014). miR-153 and miR-335, ethanol sensitive microRNAs, control NSC/NPC maturation during fetal brain development. Lang. Cognit. Processes 15, 87–127.Search in Google Scholar

Tsai, M.C., Chang, C.P., Peng, S.W., Jhuang, K.S., Fang, Y.H., Lin, M.T., and Tsao, T.C. (2015). Therapeutic efficacy of neuro AiD™ (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury. J. Neuroimmune Pharm. 10, 45–54.10.1007/s11481-014-9570-0Search in Google Scholar PubMed

Walder, B., Haller, G., Rebetez, M.M., Delhumeau, C., Bottequin, E., Schoettker, P., Ravussin, P., Brodmann, M.M., Stover, J.F., Zürcher, M., et al. (2013). Severe traumatic brain injury in a high-income country: an epidemiological study. J. Neurotrauma. 30, 1934–1942.10.1089/neu.2013.2955Search in Google Scholar PubMed

Wang, C.F., Zhao, C.C., Weng, W.J., Lei, J., Lin, Y., Mao, Q., Gao, G.Y., Feng, J.F., and Jiang, J.Y. (2017). Alteration in long non-coding RNA expression after traumatic brain injury in rats. J. Neurotraum. 34, 2100–2108.10.1089/neu.2016.4642Search in Google Scholar PubMed

Wang, F., Hongwei, T., Li, L., Piontek, K., Sakaguchi, M., and Selaru, F.M. (2018). Exosome – miR-335 as a novel therapeutic strategy in hepatocellular carcinoma. Hepatology 67, 940–954.10.1002/hep.29586Search in Google Scholar PubMed PubMed Central

Wu, X., Mao, H., Liu, J., Xu, J., Cao, J., Gu, X., and Cui, G. (2013). Dynamic change of SGK expression and its role in neuron apoptosis after traumatic brain injury. Int. J. Clin. Exp. Pathol. 6, 1282.Search in Google Scholar

Xing, Z., Xia, Z., Peng, W., Li, J., Zhang, C., Fu, C., Tang, T., Luo, J., Zou, Y., and Fan, R. (2016). Xuefu zhuyu decoction, a traditional Chinese medicine, provides neuroprotection in a rat model of traumatic brain injury via an anti-inflammatory pathway. Sci. Rep. 6, 20040.10.1038/srep20040Search in Google Scholar PubMed PubMed Central

Yang, B., Huang, J., Hao, L., Guo, W., and Li, G. (2016). miR-335 directly, while miR-34a indirectly modulate survivin expression and regulate growth, apoptosis, and invasion of gastric cancer cells. Tumour Biol. 37, 1771–1779.10.1007/s13277-015-3951-8Search in Google Scholar PubMed

Received: 2018-08-08
Accepted: 2019-01-03
Published Online: 2019-01-17
Published in Print: 2019-06-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

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