Effect of poly‑arginine R18 on neurocyte cell growth via autophagy in traumatic brain injury

Batulu,Hu; Du,Guo‑Jia; Li,Da‑Zhi; Sailike,Duishanbai; Fan,Yu‑Hua; Geng,Dangmurenjiafu

doi:10.3892/etm.2019.7423

Effect of poly‑arginine R18 on neurocyte cell growth via autophagy in traumatic brain injury

Authors:
- Hu Batulu
- Guo‑Jia Du
- Da‑Zhi Li
- Duishanbai Sailike
- Yu‑Hua Fan
- Dangmurenjiafu Geng
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, P.R. China, Department of Neurosurgery, Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830000, P.R. China, Department of Nutrition Section, The People's Hospital of Xinjiang Bortala Autonomous Prefecture of Monglia, Bortala, Xinjiang 833400, P.R. China
Published online on: March 20, 2019 https://doi.org/10.3892/etm.2019.7423
Pages: 4109-4115
Copyright: © Batulu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study assessed the effects of poly‑arginine R18 and its promotion of neurocyte cell growth via autophagy in traumatic brain injury (TBI), and aimed to determine the possible mechanism by which this occurs. Brain water content was measured to analyze the effects of poly‑arginine R18 in TBI. MTT and lactate dehydrogenase activity assays were performed to measure N2A cell growth. Western blotting and immunofluorescence staining were also performed to determine the protein expression of Bcl‑2 associated X, LC3, Beclin‑1 and p62. The results demonstrated that poly‑arginine R18 treatment reduced neurocyte apoptosis and promoted neurocyte cell growth via the activation of autophagy in a rat model of TBI. Furthermore, poly‑arginine R18 treatment promoted neurocyte cell growth, reduced apoptosis, induced the protein expression of LC3 and Beclin‑1, and suppressed p62 expression by promoting autophagy in vitro. In addition, the inhibition of autophagy attenuated the effects of poly‑arginine R18 on cell growth in vitro. Collectively, the results demonstrate the effects of poly‑arginine R18 on neurocyte cell growth via autophagy activation in a model of TBI, and poly‑arginine R18 is therefore a potential therapeutic target in TBI.

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1	Yang Z, Lin F, Robertson CS and Wang KK: Dual vulnerability of TDP-43 to calpain and caspase-3 proteolysis after neurotoxic conditions and traumatic brain injury. J Cereb Blood Flow Metab. 34:1444–1452. 2014. View Article : Google Scholar : PubMed/NCBI
2	Okonkwo DO, Shutter LA, Moore C, Temkin NR, Puccio AM, Madden CJ, Andaluz N, Chesnut RM, Bullock MR, Grant GA, et al: Brain oxygen optimization in severe traumatic brain injury Phase-II: A Phase II randomized trial. Crit Care Med. 45:1907–1914. 2017. View Article : Google Scholar : PubMed/NCBI
3	Grima NA, Rajaratnam SMW, Mansfield D, Sletten TL, Spitz G and Ponsford JL: Efficacy of melatonin for sleep disturbance following traumatic brain injury: A randomised controlled trial. BMC Med. 16:82018. View Article : Google Scholar : PubMed/NCBI
4	Sun L, Zhao M, Wang Y, Liu A, Lv M, Li Y, Yang X and Wu Z: Neuroprotective effects of miR-27a against traumatic brain injury via suppressing FoxO3a-mediated neuronal autophagy. Biochem Biophys Res Commun. 482:1141–1147. 2017. View Article : Google Scholar : PubMed/NCBI
5	Zeng XJ, Li P, Ning YL, Zhao Y, Peng Y, Yang N, Zhao ZA, Chen JF and Zhou YG: Impaired autophagic flux is associated with the severity of trauma and the role of A_2AR in brain cells after traumatic brain injury. Cell Death Dis. 9:2522018. View Article : Google Scholar : PubMed/NCBI
6	Chen X, Wang H, Zhou M, Li X, Fang Z, Gao H, Li Y and Hu W: Valproic acid attenuates traumatic brain injury-induced inflammation in vivo: Involvement of autophagy and the Nrf2/ARE signaling pathway. Front Mol Neurosci. 11:1172018. View Article : Google Scholar : PubMed/NCBI
7	Milani D, Knuckey NW, Anderton RS, Cross JL and Meloni BP: The R18 polyarginine peptide is more effective than the TAT-NR2B9c (NA-1) peptide when administered 60 minutes after permanent middle cerebral artery occlusion in the rat. Stroke Res Treat. 2016:23727102016.PubMed/NCBI
8	Cui C, Cui J, Jin F, Cui Y, Li R, Jiang X, Tian Y, Wang K, Jiang P and Gao J: Induction of the Vitamin D receptor attenuates autophagy dysfunction-mediated cell death following traumatic brain injury. Cell Physiol Biochem. 42:1888–1896. 2017. View Article : Google Scholar : PubMed/NCBI
9	Milani D, Bakeberg MC, Cross JL, Clark VW, Anderton RS, Blacker DJ, Knuckey NW and Meloni BP: Comparison of neuroprotective efficacy of poly-arginine R18 and R18D (D-enantiomer) peptides following permanent middle cerebral artery occlusion in the Wistar rat and in vitro toxicity studies. PLoS One. 13:e01938842018. View Article : Google Scholar : PubMed/NCBI
10	Blaha RZ, Arnett AB, Kirkwood MW, Taylor HG, Stancin T, Brown TM and Wade SL: Factors influencing attrition in a multisite, randomized, clinical trial following traumatic brain injury in adolescence. J Head Trauma Rehabil. 30:E33–E40. 2015. View Article : Google Scholar : PubMed/NCBI
11	Hammond FM, Alexander DN, Cutler AJ, D'Amico S, Doody RS, Sauve W, Zorowitz RD, Davis CS, Shin P, Ledon F, et al: PRISM II: An open-label study to assess effectiveness of dextromethorphan/quinidine for pseudobulbar affect in patients with dementia, stroke or traumatic brain injury. BMC Neurol. 16:892016. View Article : Google Scholar : PubMed/NCBI
12	Beca J, McSharry B, Erickson S, Yung M, Schibler A, Slater A, Wilkins B, Singhal A, Williams G, Sherring C, et al: Hypothermia for traumatic brain injury in children-a phase II randomized controlled trial. Crit Care Med. 43:1458–1466. 2015. View Article : Google Scholar : PubMed/NCBI
13	Renaud MI, Lambregts SA, de Kloet AJ, Catsman-Berrevoets CE, van de Port IG and van Heugten CM: Activities and participation of children and adolescents after mild traumatic brain injury and the effectiveness of an early intervention (Brains Ahead!): Study protocol for a cohort study with a nested randomised controlled trial. Trials. 17:2362016. View Article : Google Scholar : PubMed/NCBI
14	Chiu LS, Anderton RS, Cross JL, Clark VW, Edwards AB, Knuckey NW and Meloni BP: Assessment of R18, COG1410, and APP96-110 in excitotoxicity and traumatic brain injury. Transl Neurosci. 8:147–157. 2017. View Article : Google Scholar : PubMed/NCBI
15	Wolf MS, Bayir H, Kochanek PM and Clark RSB: The role of autophagy in acute brain injury: A state of flux? Neurobiol Dis. 122:9–15. 2019. View Article : Google Scholar : PubMed/NCBI
16	Sun LQ, Gao JL, Cui Y, Zhao MM, Jing XB, Li R, Tian YX, Cui JZ and Wu ZX: Neuronic autophagy contributes to p-connexin 43 degradation in hippocampal astrocytes following traumatic brain injury in rats. Mol Med Rep. 11:4419–4423. 2015. View Article : Google Scholar : PubMed/NCBI
17	Jin Y, Lin Y, Feng JF, Jia F, Gao G and Jiang JY: Attenuation of cell death in injured cortex after post-traumatic brain injury moderate hypothermia: Possible involvement of autophagy pathway. World Neurosurg. 84:420–430. 2015. View Article : Google Scholar : PubMed/NCBI
18	Cordaro M, Impellizzeri D, Paterniti I, Bruschetta G, Siracusa R, De Stefano D, Cuzzocrea S and Esposito E: Neuroprotective effects of Co-UltraPEALut on secondary inflammatory process and autophagy involved in traumatic brain injury. J Neurotrauma. 33:132–146. 2016. View Article : Google Scholar : PubMed/NCBI