Abstract
Subarachnoid hemorrhage is a common disease in the neural system, which causes high fatality rate. Therefore, it is necessary to figure out inner mechanisms of factors related to this disease. RT-qPCR was applied for measuring expressions of CDKN1B and miR-502-5p and other factors of apoptosis and inflammation. Cell viabilities were detected through CCK-8. Binding conditions between miR-502-5p and CDKN1B were detected through luciferase report assay. Western blot was used for measuring levels of proteins in PPARγ/NF-κB signaling pathway. Apoptosis and inflammation of HT22 cell line, a kind of nerve cell line, were enhanced and viabilities were suppressed by oxyhemoglobin. CDKN1B expressed lower in induced HT22 cell line and overexpressed CDKN1B could promote viabilities and suppress apoptosis as well as inflammation. MiR-502-5p was the target gene of CDKN1B and enhanced apoptosis and inflammation of cells in HT22 cell line. Furthermore, miR-502-5p reversed functions of CKDN1B in induced cells through regulating proteins in PPARγ/NF-κB signaling pathway. CDKN1B was the gene that could inhibit SAH caused by apoptosis in nerve cells and inflammation by sponging miR-502-5p and regulating factors in PPARγ/NF-κB signaling pathway, suggesting it could be a factor for protecting functions of nerve cells after SAH.
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References
Aupperlee MD, Kariagina A, Zaremba N, Basson MD, Schwartz RC, Haslam SZ (2018) The proliferative response to p27 down-regulation in estrogen plus progestin hormonal therapy is lost in breast tumors. Transl Oncol 11(2):518–527
Bederson JB, Connolly ES Jr, Batjer HH, Dacey RG, Dion JE, Diringer MN et al (2009) Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 40(3):994–1025
Chen LJ, Chuang L, Huang YH, Zhou J, Lim SH, Lee CI, Lin WW, Lin TE, Wang WL, Chen L, Chien S, Chiu JJ (2015) MicroRNA mediation of endothelial inflammatory response to smooth muscle cells and its inhibition by atheroprotective shear stress. Circ Res 116(7):1157–1169
de Rooij NK, Linn FH, van der Plas JA, Algra A, Rinkel GJ (2007) Incidence of subarachnoid haemorrhage: a systematic review with emphasis on region, age, gender and time trends. J Neurol Neurosurg Psychiatry 78(12):1365–1372
Do SI, Kim DH, Yang JH, Pyo JS, Kim K, Lee H, Do IG, Kim DH, Chae SW, Sohn JH (2016) Decreased expression of p27 is associated with malignant transformation and extrathyroidal extension in papillary thyroid carcinoma. Tumor Biol 37(3):3359–3364
Dutta J, Fan Y, Gupta N, Fan G, Gelinas C (2006) Current insights into the regulation of programmed cell death by NF-κ B. Oncogene 25(51):6800–6816
Gladine C, Laurie JC, Giulia C, Dominique B, Corinne C, Nathalie H (2014) Neuroprostanes, produced by free-radical mediated peroxidation of DHA, inhibit the inflammatory response of human macrophages. Free Radic Biol Med 75:S15
Goto T, Mitsuhashi T, Takahashi T (2004) Altered patterns of neuron production in the p27Kip1 knockout mouse. Dev Neurosci 26(2–4):208–217
Graham I, Cooney MT, Bradley D, Dudina A, Reiner Z (2012) Dyslipidemias in the prevention of cardiovascular disease: risks and causality. Curr Cardiol Rep 14(6):709–720
Grey W, Izatt L, Sahraoui W, Ng YM, Ogilvie C, Hulse A, Tse E, Holic R, Yu V. (2013). Deficiency of the cyclin-dependent kinase inhibitor, CDKN 1 B, Results in Overgrowth and
Guan YY, Weir BK, Marton LS, Macdonald RL, Zhang H (1998) Effects of erythrocyte lysate of different incubation times on intracellular free calcium in rat basilar artery smooth-muscle cells. J Neurosurg 89(6):1007–1014
Hasegawa Y, Suzuki H, Sozen T, Altay O, Zhang JH (2011) Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemorrhage. In: Early Brain Injury or Cerebral Vasospasm. Springer, Vienna, pp 43–48
Hotchkiss RS, Strasser A, McDunn JE, Swanson PE (2009) Cell death. N Engl J Med 361(16):1570–1583
Huang LT, Li H, Sun Q, Liu M, Li S, Yu Z, Wei WT, Hang CH (2015) IL-33 expression in the cerebral cortex following experimental subarachnoid hemorrhage in rats. Cell Mol Neurobiol 35(4):493–501
Kiyokawa H, Kineman RD, Manova-Todorova KO, Soares VC, Hoffman ES, Ono M, Khanam D, Hayday AC, Frohman LA, Koff A (1996) Enhanced growth of mice lacking the cyclin-dependent kinase inhibitor function of p27Kip1. Cell 85(5):721–732
Lai NS, Zhang JQ, Qin FY, Sheng B, Fang XG, Li ZB (2017) Serum microRNAs are non-invasive biomarkers for the presence and progression of subarachnoid haemorrhage. Biosci Rep 37(1)
Miller BA, Turan N, Chau M, Pradilla G (2014) Inflammation, vasospasm, and brain injury after subarachnoid hemorrhage. BioMed Res Int 2014:384342
Nakagomi T, Kassell NF, Sasaki T, Lehman RM, Torner JC, Hongo K, Lee JH (1988) Effect of removal of the endothelium on vasocontraction in canine and rabbit basilar arteries. J Neurosurg 68(5):757–766
Pasquinelli AE, Reinhart BJ, Slack F, Martindale MQ, Kuroda MI, Maller B, Hayward DC, Ball EE, Degnan B, Müller P, Spring J (2000) Conservation of the sequence and temporal expression of let-7 heterochronic regulatory RNA. Nature 408(6808):86–89
Perry JJ, Stiell IG, Sivilotti ML, Bullard MJ, Lee JS, Eisenhauer M et al (2010) High risk clinical characteristics for subarachnoid haemorrhage in patients with acute headache: prospective cohort study. Bmj 341:c5204
Petridis AK, Kamp MA, Cornelius JF, Beez T, Beseoglu K, Turowski B, Steiger HJ (2017) Aneurysmal subarachnoid hemorrhage: diagnosis and treatment. Dtsch Arztebl Int 114(13):226–236
Pluta RM, Afshar JK, Boock RJ, Oldfield EH (1998) Temporal changes in perivascular concentrations of oxyhemoglobin, deoxyhemoglobin, and methemoglobin after subarachnoid hemorrhage. J Neurosurg 88(3):557–561
Reis De Almeida M, Pérez-Sayáns M, Suárez-Peñaranda JM, Somoza-Martín JM, García-García A (2015) p27Kip1 expression as a prognostic marker for squamous cell carcinoma of the head and neck. Oncol Lett 10(5):2675–2682
Selvamani A, Williams MH, Miranda RC, Sohrabji F (2014) Circulating miRNA profiles provide a biomarker for severity of stroke outcomes associated with age and sex in a rat model. Clin Sci 127(2):77–89
Song JP, Mao Y, Song DL, Leng B, Gu YX (2009) Relationship between characteristic geometry and risk of rupture in cerebral saccular aneurysm. Zhonghua Yi Xue Za Zhi 89(11):732–735
Van Gijn J, Kerr RS, Rinkel GJ (2007) Subarachnoid haemorrhage. Lancet 369(9558):306–318
Vlak MH, Algra A, Brandenburg R, Rinkel GJ (2011) Prevalence of unruptured intracranial aneurysms, with emphasis on sex, age, comorbidity, country, and time period: a systematic review and meta-analysis. The Lancet Neurology 10(7):626–636
Von Zychlinski A, Kleffmann T, Williams MJ, McCormick SP (2011) Proteomics of lipoprotein (a) identifies a protein complement associated with response to wounding. J Proteome 74(12):2881–2891
Wang WX, Visavadiya NP, Pandya JD, Nelson PT, Sullivan PG, Springer JE et al (2015) Mitochondria-associated microRNAs in rat hippocampus following traumatic brain injury. Exp Neurol 265:84–93
Wermer MJ, van der Schaaf IC, Algra A, Rinkel GJ (2007) Risk of rupture of unruptured intracranial aneurysms in relation to patient and aneurysm characteristics: an updated meta-analysis. Stroke 38(4):1404–1410
Zhu Q, Enkhjargal B, Huang L, Zhang T, Sun C, Xie Z, Wu P, Mo J, Tang J, Xie Z, Zhang JH (2018) Aggf1 attenuates neuroinflammation and BBB disruption via PI3K/Akt/NF-κB pathway after subarachnoid hemorrhage in rats. J Neuroinflammation 15(1):178
Zhong S, Li YG, Ji DF, Lin TB, Lv ZQ (2016) Protocatechualdehyde induces S-phase arrest and apoptosis by stimulating the p27(KIP1)-Cyclin A/D1-CDK2 and mitochondrial apoptotic pathways in HT-29 cells. Molecules 21(7):934
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Dong Chen—concepts, design, data analysis, statistical analysis, manuscript preparation, manuscript review, guarantor.
Xianwei Wang—concepts, design, data analysis, statistical analysis, manuscript preparation, manuscript review, guarantor.
Jiaming Huang—concepts, design, data analysis, statistical analysis, manuscript preparation, manuscript review, guarantor.
Sifu Cui—definition of intellectual content, literature search, experimental studies, data acquisition, manuscript editing.
Liqiang Zhang—definition of intellectual content, literature search, experimental studies, data acquisition, manuscript editing.
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Ethical approval was obtained from IEC of Dalian Municipal Central Hospital Affiliated of Dalian Medical University, Dalian, Liaoning Province, China.
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Data sharing is not applicable to this article as no new data were created or analyzed in this study. All the generated data are available in this article itself. The raw data that support the findings of this study are available from the corresponding author upon reasonable request.
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Chen, D., Wang, X., Huang, J. et al. CDKN1B Mediates Apoptosis of Neuronal Cells and Inflammation Induced by Oxyhemoglobin via miR-502-5p After Subarachnoid Hemorrhage. J Mol Neurosci 70, 1073–1080 (2020). https://doi.org/10.1007/s12031-020-01512-z
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DOI: https://doi.org/10.1007/s12031-020-01512-z