miR‑128 is upregulated in epilepsy and promotes apoptosis through the SIRT1 cascade

Chen,De‑Zhe; Wang,Wei‑Wei; Chen,Yan‑Ling; Yang,Xia‑Feng; Zhao,Min; Yang,Yan‑Yan

doi:10.3892/ijmm.2019.4223

miR‑128 is upregulated in epilepsy and promotes apoptosis through the SIRT1 cascade

Authors:
- De‑Zhe Chen
- Wei‑Wei Wang
- Yan‑Ling Chen
- Xia‑Feng Yang
- Min Zhao
- Yan‑Yan Yang
View Affiliations

Affiliations: Department of Neurology, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China, Department of Neurology, Taishan Medical University, Taian, Shandong 271016, P.R. China
Published online on: May 30, 2019 https://doi.org/10.3892/ijmm.2019.4223
Pages: 694-704

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The present study aimed to examine the functional and molecular effects of miR‑128 in epilepsy, in order to investigate its potential protective mechanisms. Firstly, miR‑128 expression in rats with lithium chloride‑induced epilepsy was demonstrated to be increased compared with the control rats. Subsequently, results from an in vitro epilepsy model demonstrated that overexpression of miR‑128 promoted nerve cell apoptosis, increased the protein expression of tumor protein p53, BCL2 associated X (Bax) and Cytochrome c, and enhanced caspase‑3/9 activity, whereas it suppressed the protein expression of sirtuin 1 (SIRT1). In addition, these alterations may be reversed by the downregulation of miR‑128. Furthermore, treatment with CAY10602, a SIRT1 agonist, reduced the effects of miR‑128 on nerve cells in vitro. Treatment with pifithrin‑β hydrobromide, a p53 inhibitor, was additionally able to mitigate the effects of miR‑128 in vitro. In conclusion, the present findings indicated that anti‑miR‑128 may exert neuroprotective effects in epilepsy, through the SIRT1/p53/Bax/Cytochrome c/caspase signaling pathway.

View Figures

View References

1	Freitas-Lima P, Alexandre V Jr, Pereira LR, Feletti F, Perucca E and Sakamoto AC: Influence of enzyme inducing antiepileptic drugs on the pharmacokinetics of levetiracetam in patients with epilepsy. Epilepsy Res. 94:117–120. 2011. View Article : Google Scholar : PubMed/NCBI
2	Abd El Naby SA and Naguib YM: Sociodemographic, electro-physiological, and biochemical profiles in children with attention deficit hyperactivity disorder and/or epilepsy. Behav Neurol. 2018:89328172018. View Article : Google Scholar
3	Angus-Leppan H: Diagnosing epilepsy in neurology clinics: A prospective study. Seizure. 17:431–436. 2008. View Article : Google Scholar : PubMed/NCBI
4	Phabphal K, Geater A, Limapichat K, Sathirapanya P, Setthawatcharawanich S and Leelawattana R: Effect of switching hepatic enzyme-inducer antiepileptic drug to levetiracetam on bone mineral density, 25 hydroxyvitamin D, and parathyroid hormone in young adult patients with epilepsy. Epilepsia. 54:e94–e98. 2013. View Article : Google Scholar : PubMed/NCBI
5	Ryvlin P, Gilliam FG, Nguyen DK, Colicchio G, Iudice A, Tinuper P, Zamponi N, Aguglia U, Wagner L, Minotti L, et al: The long-term effect of vagus nerve stimulation on quality of life in patients with pharmacoresistant focal epilepsy: The PuLsE (Open Prospective Randomized Long-term Effectiveness) trial. Epilepsia. 55:893–900. 2014. View Article : Google Scholar : PubMed/NCBI
6	Dalal K, Devarajan E, Pandey RM, Subbiah V and Tripathi M: Role of reflexology and antiepileptic drugs in managing intractable epilepsy-a randomized controlled trial. Forsch Komplementmed. 20:104–111. 2013. View Article : Google Scholar
7	Reschke CR and Henshall DC: microRNA and Epilepsy. Adv Exp Med Biol. 888:41–70. 2015. View Article : Google Scholar : PubMed/NCBI
8	Moon J, Lee ST, Choi J, Jung KH, Yang H, Khalid A, Kim JM, Park KI, Shin JW, Ban JJ, et al: Unique behavioral characteristics and microRNA signatures in a drug resistant epilepsy model. PLoS One. 9:e856172014. View Article : Google Scholar : PubMed/NCBI
9	Srivastava A, Dixit AB, Banerjee J, Tripathi M and Sarat Chandra P: Role of inflammation and its miRNA based regulation in epilepsy: Implications for therapy. Clin Chim Acta. 452:1–9. 2015. View Article : Google Scholar : PubMed/NCBI
10	Li MM, Li XM, Zheng XP, Yu JT and Tan L: MicroRNAs dysregulation in epilepsy. Brain Res. 1584:94–104. 2014. View Article : Google Scholar
11	Hall AM, Brennan GP, Nguyen TM, Singh-Taylor A, Mun HS, Sargious MJ and Baram TZ: The Role of Sirt1 in Epileptogenesis. eNeuro. 4:ENEURO.0301–16.2017. 2017. View Article : Google Scholar
12	Wang D, Li Z, Zhang Y, Wang G, Wei M, Hu Y, Ma S, Jiang Y, Che N, Wang X, et al: Targeting of microRNA-199a-5p protects against pilocarpine-induced status epilepticus and seizure damage via SIRT1-p53 cascade. Epilepsia. 57:706–716. 2016. View Article : Google Scholar : PubMed/NCBI
13	Alsharafi W and Xiao B: Dynamic expression of MicroRNAs (183, 135a, 125b, 128, 30c and 27a) in the rat pilocarpine model and temporal lobe epilepsy patients. CNS Neurol Disord Drug Targets. 14:1096–1102. 2015. View Article : Google Scholar : PubMed/NCBI
14	Wang L, Liang L, Yang T, Qiao Y, Xia Y, Liu L, Li C, Lu P and Jiang X: A pilot clinical study of apatinib plus irinotecan in patients with recurrent high-grade glioma: Clinical trial/experimental study. Medicine (Baltimore). 96:e90532017. View Article : Google Scholar
15	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar
16	Chen L, Zheng H and Zhang S: Involvement of upregulation of miR-210 in a rat epilepsy model. Neuropsychiatr Dis Treat. 12:1731–1737. 2016. View Article : Google Scholar : PubMed/NCBI
17	Wang XM, Jia RH, Wei D, Cui WY and Jiang W: MiR-134 blockade prevents status epilepticus like-activity and is neuro-protective in cultured hippocampal neurons. Neurosci Lett. 572:20–25. 2014. View Article : Google Scholar : PubMed/NCBI
18	Wang W, Zhang J, Li Y, Yang X, He Y, Li T, Ren F, Zhang J and Lin R: Divalproex sodium enhances the anti-leukemic effects of imatinib in chronic myeloid leukemia cells partly through SIRT1. Cancer Lett. 356:791–799. 2015. View Article : Google Scholar
19	Qian C, Jin J, Chen J, Li J, Yu X, Mo H and Chen G: SIRT1 activation by resveratrol reduces brain edema and neuronal apoptosis in an experimental rat subarachnoid hemorrhage model. Mol Med Rep. 16:9627–9635. 2017. View Article : Google Scholar : PubMed/NCBI
20	Adlakha YK and Saini N: miR-128 exerts pro-apoptotic effect in a p53 transcription-dependent and -independent manner via PUMA-Bak axis. Cell Death Dis. 4:e5422013. View Article : Google Scholar : PubMed/NCBI
21	Lages E, Guttin A, El Atifi M, Ramus C, Ipas H, Dupré I, Rolland D, Salon C, Godfraind C, deFraipont F, et al: MicroRNA and target protein patterns reveal physiopathological features of glioma subtypes. PLoS One. 6:e206002011. View Article : Google Scholar : PubMed/NCBI
22	Engel T, Murphy BM, Schindler CK and Henshall DC: Elevated p53 and lower MDM2 expression in hippocampus from patients with intractable temporal lobe epilepsy. Epilepsy Res. 77:151–156. 2007. View Article : Google Scholar : PubMed/NCBI
23	Araki T, Shinoda S, Schindler CK, Quan-Lan J, Meller R, Taki W, Simon RP and Henshall DC: Expression, interaction, and proteolysis of death-associated protein kinase and p53 within vulnerable and resistant hippocampal subfields following seizures. Hippocampus. 14:326–336. 2004. View Article : Google Scholar : PubMed/NCBI
24	Zhao H, Lin G, Shi M, Gao J, Wang Y, Wang H, Sun H and Cao Y: The mechanism of neurogenic pulmonary edema in epilepsy. J Physiol Sci. 64:65–72. 2014. View Article : Google Scholar
25	Rabie T, Mühlhofer W, Bruckner T, Schwab A, Bauer AT, Zimmermann M, Bonke D, Marti HH and Schenkel J: Transient protective effect of B-vitamins in experimental epilepsy in the mouse brain. J Mol Neurosci. 41:74–79. 2010. View Article : Google Scholar