Upregulation of miR-215 attenuates propofol-induced apoptosis and oxidative stress in developing neurons by targeting LATS2
Tóm tắt
Propofol is an intravenous anesthetic agent that commonly induces significant neuroapoptosis. MicroRNAs (miRNAs) have been reported to participate in the regulation of propofol exposure-mediated neurotoxicity. MiR-215, as one of miRNAs, was found to regulate nerve cell survival. However, the mechanism through which miRNAs regulate propofol exposure-mediated neurotoxicity is still unclear. Real-time PCR was used to detect miR-215 expression level. Cell viability was measured using MTT assay. Cell apoptosis was examined via flow cytometry analysis. ROS, MDA, LDH and SOD levels were assayed through ELISA kits. Dual luciferase reporter assay identified the interaction between miR-215 and large tumor suppressor 2 (LATS2). Protein level was detected using western blot analysis. MiR-215 expression was downregulated in propofol-treated rat hippocampal neurons. MiR-215 mimics promoted cell viability and reduced apoptosis in propofol-treated neonatal rat hippocampal neuron. MiR-215 mimics also caused inhibition of oxidative stress as evidenced by suppression of ROS, MDA and LDH levels as well as increase of SOD level. In addition, we found that large tumor suppressor 2 (LATS2) is a target of miR-215 and miR-215 mimics decreased LATS2 level in propofol-treated neonatal rat hippocampal neuron. Further, LATS2 overexpression suppressed the effect of miR-215 on propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron. Taken together, we demonstrate that miR-215 attenuates propofol-induced apoptosis and oxidative stress in neonatal rat hippocampal neuron by targeting LATS2, suggesting that miR-215 may provide a new candidate for the treatment of propofol exposure-induced neurotoxicity.
Tài liệu tham khảo
Aon MA, Cortassa S, O'Rourke B. Redox-optimized ROS balance: a unifying hypothesis. Biochim Biophys Acta. 2010;1797:865–77.
Asikainen S, Rudgalvyte M, Heikkinen L, Louhiranta K, Lakso M, Wong G, et al. Global microRNA expression profiling of Caenorhabditis elegans Parkinson's disease models. J Mol Neurosci. 2010;41:210–8.
Aylon Y, Michael D, Shmueli A, Yabuta N, Nojima H, Oren M. A positive feedback loop between the p53 and Lats2 tumor suppressors prevents tetraploidization. Genes Dev. 2006;20:2687–700.
Aylon Y, Ofir-Rosenfeld Y, Yabuta N, Lapi E, Nojima H, Lu X, et al. The Lats2 tumor suppressor augments p53-mediated apoptosis by promoting the nuclear proapoptotic function of ASPP1. Genes Dev. 2010;24:2420–9.
Bartel DP. MicroRNAs: target recognition and regulatory functions. Cell. 2009;136:215–33.
Bhargava N, Das M, Edwards D, Stancescu M, Kang JF, Hickman JJ. Coexpression of glutamate vesicular transporter (VGLUT1) and choline acetyltransferase (ChAT) proteins in fetal rat hippocampal neurons in culture. In Vitro Cell Dev Biol Anim. 2010;46:685–92.
Bosnjak ZJ, Logan S, Liu Y, Bai X. Recent insights into molecular mechanisms of Propofol-induced developmental neurotoxicity: implications for the protective strategies. Anesth Analg. 2016;123:1286–96.
Brandt ZJ, North PN, Link BA. Somatic mutations of lats2 cause peripheral nerve sheath tumors in Zebrafish. Cells. 2019;8:972.
Chidambaran V, Costandi A, D'Mello A. Propofol: a review of its role in pediatric anesthesia and sedation. CNS Drugs. 2015;29:543–63.
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;43:648–51.
Fabian MR, Sonenberg N, Filipowicz W. Regulation of mRNA translation and stability by microRNAs. Annu Rev Biochem. 2010;79:351–79.
Hao W, Zhao ZH, Meng QT, Tie ME, Lei SQ, Xia ZY. Propofol protects against hepatic ischemia/reperfusion injury via miR-133a-5p regulating the expression of MAPK6. Cell Biol Int. 2017;41:495–504.
Hebert SS, Horre K, Nicolai L, Papadopoulou AS, Mandemakers W, Silahtaroglu AN, et al. Loss of microRNA cluster miR-29a/b-1 in sporadic Alzheimer's disease correlates with increased BACE1/beta-secretase expression. Proc Natl Acad Sci U S A. 2008;105:6415–20.
Huang Q, Wu YT, Tan HL, Ong CN, Shen HM. A novel function of poly(ADP-ribose) polymerase-1 in modulation of autophagy and necrosis under oxidative stress. Cell Death Differ. 2009;16:264–77.
Ji Y, Wang D, Zhang B, Lu H. MiR-361-3p inhibits beta-amyloid accumulation and attenuates cognitive deficits through targeting BACE1 in Alzheimer's disease. J Integr Neurosci. 2019;18:285–91.
Jiang Q, Wang Y, Shi X. Propofol inhibits neurogenesis of rat neural stem cells by Upregulating MicroRNA-141-3p. Stem Cells Dev. 2017;26:189–96.
Johnson R, Zuccato C, Belyaev ND, Guest DJ, Cattaneo E, Buckley NJ. A microRNA-based gene dysregulation pathway in Huntington's disease. Neurobiol Dis. 2008;29:438–45.
Kaur P, Armugam A, Jeyaseelan K. MicroRNAs in neurotoxicity. J Toxicol. 2012;2012:870150.
Ke H, Pei J, Ni Z, Xia H, Qi H, Woods T, et al. Putative tumor suppressor Lats2 induces apoptosis through downregulation of Bcl-2 and Bcl-x(L). Exp Cell Res. 2004;298:329–38.
Lee YM, Song BC, Yeum KJ. Impact of volatile anesthetics on oxidative stress and inflammation. Biomed Res Int. 2015;2015:242709.
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.
Rodrigo S, Rodriguez L, Otero P, Panadero MI, Garcia A, Barbas C, et al. Fructose during pregnancy provokes fetal oxidative stress: the key role of the placental heme oxygenase-1. Mol Nutr Food Res. 2016;60:2700–11.
Shukla GC, Singh J, Barik S. MicroRNAs: processing, maturation, target recognition and regulatory functions. Mol Cell Pharmacol. 2011;3:83–92.
Su R, Sun P, Zhang D, Xiao W, Feng C, Zhong L. Neuroprotective effect of miR-410-3p against sevoflurane anesthesia-induced cognitive dysfunction in rats through PI3K/Akt signaling pathway via targeting C-X-C motif chemokine receptor 5. Genes Genomics. 2019;41:1223–31.
Sun H, Zhong D, Jin J, Liu Q, Wang H, Li G. Upregulation of miR-215 exerts neuroprotection effects against ischemic injury via negative regulation of Act1/IL-17RA signaling. Neurosci Lett. 2018;662:233–41.
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.
Sun WC, Pei L. Rno-miR-665 targets BCL2L1 (BCL-xl) and increases vulnerability to propofol in developing astrocytes. J Neurochem. 2016;138:233–42.
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;121:786–800.
Unoki M, Nakamura Y. Growth-suppressive effects of BPOZ and EGR2, two genes involved in the PTEN signaling pathway. Oncogene. 2001;20:4457–65.
Wang X, Ding G, Lai W, Liu S, Shuai J. MicroRNA-383 upregulation protects against propofol-induced hippocampal neuron apoptosis and cognitive impairment. Exper Therapeutic Med. 2018a;15:3181–8.
Wang Y, Branicky R, Noe A, Hekimi S. Superoxide dismutases: dual roles in controlling ROS damage and regulating ROS signaling. J Cell Biol. 2018b;217:1915–28.
Wei H. The role of calcium dysregulation in anesthetic-mediated neurotoxicity. Anesth Analg. 2011;113:972–4.
Yabuta N, Fujii T, Copeland NG, Gilbert DJ, Jenkins NA, Nishiguchi H, et al. Structure, expression, and chromosome mapping of LATS2, a mammalian homologue of the Drosophila tumor suppressor gene LATS/warts. Genomics. 2000;63:263–70.
Zhang H, Deo M, Thompson RC, Uhler MD, Turner DL. Negative regulation of yap during neuronal differentiation. Dev Biol. 2012;361:103–15.
Zhang S, Liang Z, Sun W, Pei L. Repeated propofol anesthesia induced downregulation of hippocampal miR-132 and learning and memory impairment of rats. Brain Res. 2017;1670:156–64.
Zheng X, Huang H, Liu J, Li M, Liu M, Luo T. Propofol attenuates inflammatory response in LPS-activated microglia by regulating the miR-155/SOCS1 pathway. Inflammation. 2018;41:11–9.