Propofol Induces the Apoptosis of Neural Stem Cells Via MicroRNA-9-5p / Chemokine CXC Receptor 4 Signaling Pathway

Overview

Journal Bioengineered

Date 2022 Jan 6

PMID 34990302

Citations 7

Authors

Weixin Zhang

Qi Liu

He Zhu

Chao Ma

Qin Luo

Meilin Ji

Li Liu

Affiliations

Soon will be listed here.

Abstract

Recent studies suggested that propofol, one of the most widely used anesthetics, may cause neurotoxicity in the developing brain, leading to cognitive deficits in adults. However, the underlying mechanisms remain unclear. In this study, we aimed to evaluate the mechanisms of propofol neurotoxicity in the neural stem cells (NSCs). The mRNA and protein expression levels of microRNA-9-5p (miR-9-5p) and chemokine CXC receptor 4 (CXCR4) were determined by quantitative reverse transcription-polymerase chain reaction and Western blotting analyses. Cell viability and apoptosis were evaluated using the cell counting kit-8 and Hoechst staining kits. The levels of apoptosis-related proteins B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 were detected by Western blotting analysis. These results confirmed that propofol activated cell apoptosis in a dose-dependent manner. A significant increase in the miR-9-5p and CXCR4 expression was observed in the propofol-treated cells. The overexpression of miR-9-5p induced apoptosis in NSCs, accompanied by elevated apoptosis-related protein activity. Furthermore, mitigated CXCR4 expression reduced propofol-induced cell apoptosis. We conclude that propofol induces cell death in NSCs, and overexpression of miR-9-5p/CXCR4 contributes to propofol-induced cell apoptosis, which might be a target for developing novel strategies to treat propofol neurotoxicity.

Citing Articles

Research progress of propofol in alleviating cerebral ischemia/reperfusion injury.

Zheng H, Xiao X, Han Y, Wang P, Zang L, Wang L Pharmacol Rep. 2024; 76(5):962-980.

PMID: 38954373 DOI: 10.1007/s43440-024-00620-6.

Neuraxial Anesthesia for Combined Left Nephrectomy and Left Hemicolectomy in a One-Lung Patient.

Vailati D, Bonvecchio E, Secco G, Magistro C, Basta B Cureus. 2024; 16(5):e59854.

PMID: 38854300 PMC: 11157490. DOI: 10.7759/cureus.59854.

Determination of the embryotoxic effects of propofol injected into eggs on the cerebellum and spinal cord using histologic methods: an animal study.

Izgi M, Sur E Turk J Med Sci. 2024; 54(1):1-15.

PMID: 38812654 PMC: 11031173. DOI: 10.55730/1300-0144.5760.

Dexmedetomidine Protects Cortical Neurons from Propofol-Induced Apoptosis via Activation of Akt-IKK-NF-κB Signaling Pathway by α-adrenoceptor.

Sun W, Li W, Zhang M, Du Q Appl Biochem Biotechnol. 2023; 196(8):4849-4861.

PMID: 37979083 DOI: 10.1007/s12010-023-04768-4.

Research progress on the effects and mechanisms of anesthetics on neural stem cells.

Zhang J, Chang Q, Rizzello L, Wu Y Ibrain. 2023; 8(4):453-464.

PMID: 37786590 PMC: 10528967. DOI: 10.1002/ibra.12071.

References

Liang C, Du F, Wang J, Cang J, Xue Z . Propofol Regulates Neural Stem Cell Proliferation and Differentiation via Calmodulin-Dependent Protein Kinase II/AMPK/ATF5 Signaling Axis. Anesth Analg. 2018; 129(2):608-617. DOI: 10.1213/ANE.0000000000003844. View

Gao M, Dong Q, Yao H, Zhang Y, Yang Y, Dang Y . Induced neural stem cells modulate microglia activation states via CXCL12/CXCR4 signaling. Brain Behav Immun. 2016; 59:288-299. DOI: 10.1016/j.bbi.2016.09.020. View

Jiang L, Yang F, Zhao Q, Pan L . MicroRNA-665 mediates propofol-induced cell apoptosis in human stem cell-derived neurons. Bioengineered. 2019; 10(1):493-500. PMC: 6844390. DOI: 10.1080/21655979.2019.1682105. View

Qiong L, Yin J . Orosomucoid 1 promotes epirubicin resistance in breast cancer by upregulating the expression of matrix metalloproteinases 2 and 9. Bioengineered. 2021; 12(1):8822-8832. PMC: 8806942. DOI: 10.1080/21655979.2021.1987067. View

Wang Z, Sun L, Jia K, Wang H, Wang X . miR-9-5p modulates the progression of Parkinson's disease by targeting SIRT1. Neurosci Lett. 2019; 701:226-233. DOI: 10.1016/j.neulet.2019.02.038. View

Yao Y, Li X, Cheng L, Wu X, Wu B . Circular RNA FAT atypical cadherin 1 (circFAT1)/microRNA-525-5p/spindle and kinetochore-associated complex subunit 1 (SKA1) axis regulates oxaliplatin resistance in breast cancer by activating the notch and Wnt signaling pathway. Bioengineered. 2021; 12(1):4032-4043. PMC: 8806415. DOI: 10.1080/21655979.2021.1951929. View

Pearn M, Schilling J, Jian M, Egawa J, Wu C, Mandyam C . Inhibition of RhoA reduces propofol-mediated growth cone collapse, axonal transport impairment, loss of synaptic connectivity, and behavioural deficits. Br J Anaesth. 2018; 120(4):745-760. PMC: 6200100. DOI: 10.1016/j.bja.2017.12.033. View

Yi J, Gao Z . MicroRNA-9-5p promotes angiogenesis but inhibits apoptosis and inflammation of high glucose-induced injury in human umbilical vascular endothelial cells by targeting CXCR4. Int J Biol Macromol. 2019; 130:1-9. DOI: 10.1016/j.ijbiomac.2019.02.003. View

Huang Y, Liu X, Wang Y . MicroRNA-378 regulates neural stem cell proliferation and differentiation in vitro by modulating Tailless expression. Biochem Biophys Res Commun. 2015; 466(2):214-20. DOI: 10.1016/j.bbrc.2015.09.011. View

10.

Liang C, Du F, Cang J, Xue Z . Pink1 attenuates propofol-induced apoptosis and oxidative stress in developing neurons. J Anesth. 2017; 32(1):62-69. DOI: 10.1007/s00540-017-2431-2. View

11.

Hu C, Iwasaki M, Liu Z, Wang B, Li X, Lin H . Lung but not brain cancer cell malignancy inhibited by commonly used anesthetic propofol during surgery: Implication of reducing cancer recurrence risk. J Adv Res. 2021; 31:1-12. PMC: 8240101. DOI: 10.1016/j.jare.2020.12.007. View

12.

Delaloy C, Liu L, Lee J, Su H, Shen F, Yang G . MicroRNA-9 coordinates proliferation and migration of human embryonic stem cell-derived neural progenitors. Cell Stem Cell. 2010; 6(4):323-335. PMC: 2851637. DOI: 10.1016/j.stem.2010.02.015. View

13.

Packer A, Xing Y, Harper S, Jones L, Davidson B . The bifunctional microRNA miR-9/miR-9* regulates REST and CoREST and is downregulated in Huntington's disease. J Neurosci. 2009; 28(53):14341-6. PMC: 3124002. DOI: 10.1523/JNEUROSCI.2390-08.2008. View

14.

Chen M, Hong C, Yue T, Li H, Duan R, Hu W . Inhibition of miR-331-3p and miR-9-5p ameliorates Alzheimer's disease by enhancing autophagy. Theranostics. 2021; 11(5):2395-2409. PMC: 7797673. DOI: 10.7150/thno.47408. View

15.

Hu Q, Huang L, Zhao C, Shen Y, Zheng X, Wang Y . Ca-PKCα-ERK1/2 signaling pathway is involved in the suppressive effect of propofol on proliferation of neural stem cells from the neonatal rat hippocampus. Brain Res Bull. 2019; 149:148-155. DOI: 10.1016/j.brainresbull.2019.04.005. View

16.

Liu J, Zhao Y, Yang J, Zhang X, Zhang W, Wang P . Neonatal Repeated Exposure to Isoflurane not Sevoflurane in Mice Reversibly Impaired Spatial Cognition at Juvenile-Age. Neurochem Res. 2016; 42(2):595-605. DOI: 10.1007/s11064-016-2114-7. View

17.

Twaroski D, Yan Y, Olson J, Bosnjak Z, 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. PMC: 4174986. DOI: 10.1097/ALN.0000000000000345. View

18.

Ho S, Ling T, Lin H, Liou J, Liu F, Chen I . SDF-1/CXCR4 Signaling Maintains Stemness Signature in Mouse Neural Stem/Progenitor Cells. Stem Cells Int. 2017; 2017:2493752. PMC: 5376953. DOI: 10.1155/2017/2493752. View

19.

Zhang L, Zhang Y, Hu R, Yan J, Huang Y, Jiang J . Isoflurane Inhibits Embryonic Stem Cell Self-Renewal and Neural Differentiation Through miR-9/E-cadherin Signaling. Stem Cells Dev. 2015; 24(16):1912-22. PMC: 4533067. DOI: 10.1089/scd.2014.0397. View

20.

Dateki M, Imamura O, Arai M, Shimizu H, Takishima K . A novel strategy for selective gene delivery by using the inhibitory effect of blue light on jetPRIME-mediated transfection. Biotechnol Bioeng. 2015; 113(7):1560-7. DOI: 10.1002/bit.25906. View