MicroRNA-582-5p Reduces Propofol-induced Apoptosis in Developing Neurons by Targeting ROCK1

Author(s): Zhongjie Zhang*, Yan Xu, Songyuan Chi, Longji Cui

Journal Name: Current Neurovascular Research

Volume 17 , Issue 2 , 2020


Become EABM
Become Reviewer
Call for Editor

Abstract:

Background: Propofol is an intravenous drug commonly used in anesthesia procedures and intensive care in children. However, it also has neurotoxic effects on children. MicroRNA plays an important role in neurological diseases and neurotoxicity.

Methods: In this study, primary rat hippocampal neurons were used to investigate the role of miR- 582-5p in propofol-induced neurotoxicity. Cell viability was monitored by 3-(4,5-dimethylthiazolyl)- 2,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the expression of proteins was monitored by real-time quantitation polymerase chain reaction (RT-qPCR) and western blot. TargetScan and double luciferase report assay were used to predict the targeting relationship between miR-582-5p and Rho-associated serine-threonine protein kinase 1 (ROCK1).

Results: In the present study, the viability of neurons and the expression of miR-582-5p were decreased in a time-dependent manner after propofol treatment. Besides, miR-582-5p overexpression significantly reduced the toxicity of propofol on neuron cells but had no significant effect on normal nerve cells. In addition, miR-582-5p overexpression significantly reversed the expression of apoptosis-related proteins (cleaved caspase 3 and cleaved caspase 9) induced by propofol but had no significant effect in normal nerve cells. TargetScan and Dual-luciferase report assay revealed that ROCK1 was a targeted regulatory gene for miR-582-5p, and propofol treatment up-regulated ROCK1 expression by inhibiting miR-582-5p expression. Notably, miR-582-5p overexpression significantly increased cell viability, while ROCK1 overexpression reversed the effect of miR-582- 5p.

Conclusion: Taken together, these findings suggest that miR-582-5p alleviated propofol-induced apoptosis of newborn rat neurons by inhibiting ROCK1.

Keywords: MicroRNA-582-5p, propofol, neurotoxicity, Rho-associated serine-threonine protein kinase1 (ROCK)1, apoptosis.

[1]
Chidambaran V, Costandi A, D’Mello A. Correction to: Propofol: A review of its role in pediatric anesthesia and sedation. CNS Drugs 2018; 32(9): 873.
[http://dx.doi.org/10.1007/s40263-018-0561-1] [PMID: 30101390]
[2]
Han D, Jin J, Fang H, Xu G. Long-term action of propofol on cognitive function and hippocampal neuroapoptosis in neonatal rats. Int J Clin Exp Med 2015; 8(7): 10696-704.
[PMID: 26379861]
[3]
Li Y, Jia C, Zhang D, et al. Propofol-induced neurotoxicity in hESCs involved in activation of miR-206/PUMA signal pathway. Cancer biomarkers: section. Dis Markers 2017; 20(2): 175-81.
[4]
Raza U, Zhang JD, Sahin O. MicroRNAs: Master regulators of drug resistance, stemness, and metastasis. J Mol Med (Berl) 2014; 92(4): 321-36.
[http://dx.doi.org/10.1007/s00109-014-1129-2] [PMID: 24509937]
[5]
Wei H. The role of calcium dysregulation in anesthetic-mediated neurotoxicity. Anesth Analg 2011; 113(5): 972-4.
[http://dx.doi.org/10.1213/ANE.0b013e3182323261] [PMID: 22021793]
[6]
Cui Y, Ling-Shan G, Yi L, Xing-Qi W, Xue-Mei Z, Xiao-Xing Y. Repeated administration of propofol upregulated the expression of c-Fos and cleaved-caspase-3 proteins in the developing mouse brain. Indian J Pharmacol 2011; 43(6): 648-51.
[PMID: 22144767]
[7]
Unoki M, Nakamura Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene 2001; 20(33): 4457-65.
[http://dx.doi.org/10.1038/sj.onc.1204608] [PMID: 11494141]
[8]
Sun WC, Liang ZD, Pei L. Propofol-induced rno-miR-665 targets BCL2L1 and influences apoptosis in rodent developing hippocampal astrocytes. Neurotoxicology 2015; 51: 87-95.
[http://dx.doi.org/10.1016/j.neuro.2015.08.001] [PMID: 26254736]
[9]
Jiang Q, Wang Y, Shi X. Propofol inhibits neurogenesis of rat neural stem cells by upregulating microRNA-141-3p. Stem Cells Dev 2017; 26(3): 189-96.
[http://dx.doi.org/10.1089/scd.2016.0257] [PMID: 27796156]
[10]
Wang X, Ding G, Lai W, Liu S, Shuai J. MicroRNA-383 upregulation protects against propofol induced hippocampal neuron apoptosis and cognitive impairment. Exp Ther Med 2018; 15(4): 3181-8.
[http://dx.doi.org/10.3892/etm.2018.5838] [PMID: 29545833]
[11]
Twaroski DM, Yan Y, Olson JM, Bosnjak ZJ, Bai X. Down-regulation of microRNA-21 is involved in the propofol induced neurotoxicity observed in human stem cell-derived neurons. Anesthesiology 2014; 121(4): 786-800.
[http://dx.doi.org/10.1097/ALN.0000000000000345] [PMID: 24950164]
[12]
Zhang X, Zhang Y, Yang J, Li S, Chen J. Upregulation of miR-582-5p inhibits cell proliferation, cell cycle progression and invasion by targeting Rab27a in human colorectal carcinoma. Cancer Gene Ther 2015; 22(10): 475-80.
[http://dx.doi.org/10.1038/cgt.2015.44] [PMID: 26384136]
[13]
Ding H, Gao S, Wang L, et al. Overexpression of miR-582-5p inhibits the apoptosis of neuronal cells after cerebral ischemic stroke through regulating PAR-1/Rho/Rho axis. J Stroke Cerebrovasc Dis 2019; 28(1): 149-55.
[14]
Chen R, Wang M, Fu S, Cao F, Duan P, Lu J. MicroRNA-204 may participate in the pathogenesis of hypoxic-ischemic encephalopathy through targeting KLLN. Exp Ther Med 2019; 18(5): 3299-306.
[http://dx.doi.org/10.3892/etm.2019.7936] [PMID: 31602202]
[15]
Kaur J, Flores Gutiérrez J, Nistri A. Neuroprotective effect of propofol against excitotoxic injury to locomotor networks of the rat spinal cord in vitro. Eur J Neurosci 2016; 44(7): 2418-30.
[http://dx.doi.org/10.1111/ejn.13353] [PMID: 27468970]
[16]
Liu F, Liu S, Patterson TA, et al. Protective effects of xenon on propofol induced neurotoxicity in human neural stem cell-derived models. Mol Neurobiol 2020; 57(1): 200-7.
[PMID: 31578707]
[17]
Jiang L, Yang F, Zhao Q, et al. MicroRNA-665 mediates propofolinduced cell apoptosis in human stem cell-derived neurons 2019; 10(1): 493-500.
[18]
Guan R, Lv J, Xiao F, Tu Y, Xie Y, Li L. Potential role of the cAMP/PKA/CREB signalling pathway in hypoxic preconditioning and effect on propofol‑induced neurotoxicity in the hippocampus of neonatal rats. Mol Med Rep 2019; 20(2): 1837-45.
[http://dx.doi.org/10.3892/mmr.2019.10397] [PMID: 31257533]
[19]
Bahmad HF, Darwish B, Dargham KB, et al. Role of microRNAs in anesthesia-induced neurotoxicity in animal models and neuronal cultures: A systematic review. Neurotox Res 2020; 37(3): 479-90.
[http://dx.doi.org/10.1007/s12640-019-00135-6] [PMID: 31707631]
[20]
Li Y, Liu Y, Fan J, et al. Validation and bioinformatic analysis of propofol induced differentially expressed microRNAs in primary cultured neural stem cells. Gene 2018; 664: 90-100.
[http://dx.doi.org/10.1016/j.gene.2018.04.046] [PMID: 29679758]
[21]
Li GF, Li ZB, Zhuang SJ, Li GC. Inhibition of microRNA-34a protects against propofol anesthesia-induced neurotoxicity and cognitive dysfunction via the MAPK/ERK signaling pathway. Neurosci Lett 2018; 675: 152-9.
[http://dx.doi.org/10.1016/j.neulet.2018.03.052] [PMID: 29578002]
[22]
Whatcott CJ, Ng S, Barrett MT, et al. Inhibition of ROCK1 kinase modulates both tumor cells and stromal fibroblasts in pancreatic cancer 2017; 12(8): e0183871.
[http://dx.doi.org/10.1371/journal.pone.0183871]
[23]
Wang Y, Wang N, Zeng X, et al. MicroRNA-335 and its target Rock1 synergistically influence tumor progression and prognosis in osteosarcoma. Oncol Lett 2017; 13(5): 3057-65.
[http://dx.doi.org/10.3892/ol.2017.5818] [PMID: 28521412]
[24]
Swanger SA, Mattheyses AL, Gentry EG, Herskowitz JH. ROCK1 and ROCK2 inhibition alters dendritic spine morphology in hippocampal neurons. Cell Logist 2016; 5(4)e1133266
[http://dx.doi.org/10.1080/21592799.2015.1133266] [PMID: 27054047]
[25]
Henderson BW, Gentry EG, Rush T, et al. Rho-associated protein kinase 1 (ROCK1) is increased in Alzheimer’s disease and ROCK1 depletion reduces amyloid-β levels in brain. J Neurochem 2016; 138(4): 525-31.
[http://dx.doi.org/10.1111/jnc.13688] [PMID: 27246255]
[26]
Feng X, Liang N, Zhu D, et al. Resveratrol inhibits β-amyloid-induced neuronal apoptosis through regulation of SIRT1-ROCK1 signaling pathway. PLoS One 2013; 8(3)e59888
[http://dx.doi.org/10.1371/journal.pone.0059888] [PMID: 23555824]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2020
Published on: 04 August, 2020
Page: [140 - 146]
Pages: 7
DOI: 10.2174/1567202617666200207124817
Price: $65

Article Metrics

PDF: 18
HTML: 2
PRC: 1