Adenosine decreases oxidative stress and protects H2O2‑treated neural stem cells against apoptosis through decreasing Mst1 expression

Gholinejad,Masoumeh; Jafari Anarkooli,Iraj; Taromchi,Amirhossein; Abdanipour,Alireza

doi:10.3892/br.2018.1083

Adenosine decreases oxidative stress and protects H2O2‑treated neural stem cells against apoptosis through decreasing Mst1 expression

Authors:
- Masoumeh Gholinejad
- Iraj Jafari Anarkooli
- Amirhossein Taromchi
- Alireza Abdanipour
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Affiliations: Department of Medical Biotechnology and Nanotechnology, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan 45139‑56184, Iran, Department of Anatomy, Faculty of Medicine, Zanjan University of Medical Sciences, Zanjan 45139‑56184, Iran
Published online on: March 27, 2018 https://doi.org/10.3892/br.2018.1083
Pages: 439-446

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Abstract

Overproduction of free radicals during oxidative stress induces damage to key biomolecules and activates programed cell death pathways. Neuronal cell death in the nervous system leads to a number of neurodegenerative diseases. The aim of the present study was to evaluate the neuroprotective effect of adenosine on inhibition of apoptosis induced by hydrogen peroxide (H2O2) in bone marrow‑derived neural stem cells (B‑dNSCs), with focus on its regulatory effect on the expression of mammalian sterile 20‑like kinase 1 (Mst1), as a novel proapoptotic kinase. B‑dNSCs were exposed to adenosine at different doses (2, 4, 6, 8 and 10 µM) for 48 h followed by 125 µM H2O2 for 30 min. Using MTT, terminal deoxynucleotidyl transferase dUTP nick‑end labeling and real‑time reverse transcription polymerase chain reaction assays, the effects of adenosine on cell survival, apoptosis and Mst1, nuclear factor (erythroid‑derived 2)‑like 2 and B‑cell lymphoma 2 and adenosine A1 receptor expression were evaluated in pretreated B‑dNSCs compared with controls (cells treated with H2O2 only). Firstly, results of the MTT assay indicated 6 µM adenosine to be the most protective dose in terms of promotion of cell viability. Subsequent assays using this dosage indicated that apoptosis rate and Mst1 expression in B‑dNSCs pretreated with 6 µM adenosine were significantly decreased compared with the control group. These findings suggest that adenosine protects B‑dNSCs against oxidative stress‑induced cell death, and therefore, that it may be used to promote the survival rate of B‑dNSCs and as a candidate for the treatment of oxidative stress‑mediated neurological diseases.

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1	Yeh LK, Liu CY, Chien CL, Converse RL, Kao WW, Chen MS, Hu FR, Hsieh FJ and Wang IJ: Molecular analysis and characterization of zebrafish keratocan (zKera) gene. J Biol Chem. 283:506–517. 2008. View Article : Google Scholar : PubMed/NCBI
2	Chen X, Guo C and Kong J: Oxidative stress in neurodegenerative diseases. Neural Regen Res. 7:376–385. 2012.PubMed/NCBI
3	Uttara B, Singh AV, Zamboni P and Mahajan RT: Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr Neuropharmacol. 7:65–74. 2009. View Article : Google Scholar : PubMed/NCBI
4	Liu Z, Liu Y, Gao R, Li H, Dunn T, Wu P, Smith RG, Sarkar PS and Fang X: Ethanol suppresses PGC-1α expression by interfering with the cAMP-CREB pathway in neuronal cells. PLoS One. 9:e1042472014. View Article : Google Scholar : PubMed/NCBI
5	Cunha RA: Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: Different roles, different sources and different receptors. Neurochem Int. 38:107–125. 2001. View Article : Google Scholar : PubMed/NCBI
6	Xu L, Xu H, Cao Y, Yang P, Feng Y, Tang Y, Yuan S and Ming J: Validation of reference genes for quantitative real-time PCR during bicolor tepal development in asiatic hybrid lilies (Lilium spp.). Front Plant Sci. 8:6692017. View Article : Google Scholar : PubMed/NCBI
7	Gorman AM: Neuronal cell death in neurodegenerative diseases: Recurring themes around protein handling. J Cell Mol Med. 12(6A): 2263–2280. 2008. View Article : Google Scholar : PubMed/NCBI
8	Gibson RM: Does apoptosis have a role in neurodegeneration? BMJ. 322:1539–1540. 2001. View Article : Google Scholar : PubMed/NCBI
9	Mattson MP: Apoptosis in neurodegenerative disorders. Nat Rev Mol Cell Biol. 1:120–129. 2000. View Article : Google Scholar : PubMed/NCBI
10	Abdanipour A, Tiraihi T and Mirnajafi-Zadeh J: Improvement of the pilocarpine epilepsy model in rat using bone marrow stromal cell therapy. Neurol Res. 33:625–632. 2011. View Article : Google Scholar : PubMed/NCBI
11	Racine RJ: Modification of seizure activity by electrical stimulation. II. Motor seizure. Electroencephalogr Clin Neurophysiol. 32:281–294. 1972. View Article : Google Scholar : PubMed/NCBI
12	Collak FK, Yagiz K, Luthringer DJ, Erkaya B and Cinar B: Threonine-120 phosphorylation regulated by phosphoinositide-3-kinase/Akt and mammalian target of rapamycin pathway signaling limits the antitumor activity of mammalian sterile 20-like kinase 1. J Biol Chem. 287:23698–23709. 2012. View Article : Google Scholar : PubMed/NCBI
13	Ardestani A, Paroni F, Azizi Z, Kaur S, Khobragade V, Yuan T, Frogne T, Tao W, Oberholzer J, Pattou F, et al: MST1 is a key regulator of beta cell apoptosis and dysfunction in diabetes. Nat Med. 20:385–397. 2014. View Article : Google Scholar : PubMed/NCBI
14	Ura S, Masuyama N, Graves JD and Gotoh Y: MST1-JNK promotes apoptosis via caspase-dependent and independent pathways. Genes Cells. 6:519–530. 2001. View Article : Google Scholar : PubMed/NCBI
15	Strom J, Xu B, Tian X and Chen QM: Nrf2 protects mitochondrial decay by oxidative stress. FASEB J. 30:66–80. 2016. View Article : Google Scholar : PubMed/NCBI
16	Murata H, Takamatsu H, Liu S, Kataoka K, Huh NH and Sakaguchi M: NRF2 regulates PINK1 expression under oxidative stress conditions. PLoS One. 10:e01424382015. View Article : Google Scholar : PubMed/NCBI
17	Zhong J and Li L: Skin-derived precursors against UVB-induced apoptosis via Bcl-2 and Nrf2 upregulation. Biomed Res Int. 2016:68947432016. View Article : Google Scholar : PubMed/NCBI
18	Maleki M, Ghanbarvand F, Behvarz Reza M, Ejtemaei M and Ghadirkhomi E: Comparison of mesenchymal stem cell markers in multiple human adult stem cells. Int J Stem Cells. 7:118–126. 2014. View Article : Google Scholar : PubMed/NCBI
19	Yang Q, Mu J, Li Q, Li A, Zeng Z, Yang J, Zhang X, Tang J and Xie P: A simple and efficient method for deriving neurospheres from bone marrow stromal cells. Biochem Biophys Res Commun. 372:520–524. 2008. View Article : Google Scholar : PubMed/NCBI
20	Suzuki S, Namiki J, Shibata S, Mastuzaki Y and Okano H: The neural stem/progenitor cell marker nestin is expressed in proliferative endothelial cells, but not in mature vasculature. J Histochem Cytochem. 58:721–730. 2010. View Article : Google Scholar : PubMed/NCBI
21	Albrecht-Küpper BE, Leineweber K and Nell PG: Partial adenosine A1 receptor agonists for cardiovascular therapies. Purinergic Signal. 8 Suppl 1:91–99. 2012. View Article : Google Scholar
22	Abbasnia K, Ghanbari A, Abedian M, Ghanbari A, Sharififar S and Azari H: The effects of repetitive transcranial magnetic stimulation on proliferation and differentiation of neural stem cells. Anat Cell Biol. 48:104–113. 2015. View Article : Google Scholar : PubMed/NCBI
23	Lee JH, Cheon YH, Woo RS, Song DY, Moon C and Baik TK: Evidence of early involvement of apoptosis inducing factor-induced neuronal death in Alzheimer brain. Anat Cell Biol. 45:26–37. 2012. View Article : Google Scholar : PubMed/NCBI
24	Mori M, Nishizaki T and Okada Y: Protective effect of adenosine on the anoxic damage of hippocampal slice. Neuroscience. 46:301–307. 1992. View Article : Google Scholar : PubMed/NCBI
25	Cunha RA: Neuroprotection by adenosine in the brain: From A(1) receptor activation to A (2A) receptor blockade. Purinergic Signal. 1:111–134. 2005. View Article : Google Scholar : PubMed/NCBI
26	Migita H, Kominami K, Higashida M, Maruyama R, Tuchida N, McDonald F, Shimada F and Sakurada K: Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways. J Neurosci Res. 86:2820–2828. 2008. View Article : Google Scholar : PubMed/NCBI
27	Elmore S: Apoptosis: A review of programmed cell death. Toxicol Pathol. 35:495–516. 2007. View Article : Google Scholar : PubMed/NCBI
28	Huang NK: Adenosine A2A receptors regulate oxidative stress formation in rat pheochromocytoma PC12 cells during serum deprivation. Neurosci Lett. 350:127–131. 2003. View Article : Google Scholar : PubMed/NCBI
29	Ramkumar V, Hallam DM and Nie Z: Adenosine, oxidative stress and cytoprotection. Jpn J Pharmacol. 86:265–274. 2001. View Article : Google Scholar : PubMed/NCBI
30	Vitolo OV, Ciotti MT, Galli C, Borsello T and Calissano P: Adenosine and ADP prevent apoptosis in cultured rat cerebellar granule cells. Brain Res. 809:297–301. 1998. View Article : Google Scholar : PubMed/NCBI
31	DeMaagd G and Philip A: Parkinson's disease and its management: Part 1: Disease entity, risk factors, pathophysiology, clinical presentation, and diagnosis. P T. 40:504–532. 2015.PubMed/NCBI
32	Zhai W, Chen D, Shen H, Chen Z, Li H, Yu Z and Chen G: A1 adenosine receptor attenuates intracerebral hemorrhage-induced secondary brain injury in rats by activating the P38-MAPKAP2-Hsp27 pathway. Mol Brain. 9:662016. View Article : Google Scholar : PubMed/NCBI
33	Meng Z, Moroishi T and Guan KL: Mechanisms of Hippo pathway regulation. Genes Dev. 30:1–17. 2016. View Article : Google Scholar : PubMed/NCBI
34	Wrann CD, White JP, Salogiannnis J, Laznik-Bogoslavski D, Wu J, Ma D, Lin JD, Greenberg ME and Spiegelman BM: Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab. 18:649–659. 2013. View Article : Google Scholar : PubMed/NCBI
35	Youdim MB: The path from anti Parkinson drug selegiline and rasagiline to multifunctional neuroprotective anti Alzheimer drugs ladostigil and m30. Curr Alzheimer Res. 3:541–550. 2006. View Article : Google Scholar : PubMed/NCBI
36	Alexander GE: Biology of Parkinson's disease: Pathogenesis and pathophysiology of a multisystem neurodegenerative disorder. Dialogues Clin Neurosci. 6:259–280. 2004.PubMed/NCBI
37	Sarkar S, Raymick J and Imam S: Neuroprotective and therapeutic strategies against Parkinson's disease: Recent Perspectives. Int J Mol Sci. 17:172016. View Article : Google Scholar
38	Pingle SC, Jajoo S, Mukherjea D, Sniderhan LF, Jhaveri KA, Marcuzzi A, Rybak LP, Maggirwar SB and Ramkumar V: Activation of the adenosine A1 receptor inhibits HIV-1 tat-induced apoptosis by reducing nuclear factor-kappaB activation and inducible nitric-oxide synthase. Mol Pharmacol. 72:856–867. 2007. View Article : Google Scholar : PubMed/NCBI
39	Han J, Talorete TP, Yamada P and Isoda H: Anti-proliferative and apoptotic effects of oleuropein and hydroxytyrosol on human breast cancer MCF-7 cells. Cytotechnology. 59:45–53. 2009. View Article : Google Scholar : PubMed/NCBI
40	Zhang Z, Zhou S, Jiang X, Wang YH, Li F, Wang YG, Zheng Y and Cai L: The role of the Nrf2/Keap1 pathway in obesity and metabolic syndrome. Rev Endocr Metab Disord. 16:35–45. 2015. View Article : Google Scholar : PubMed/NCBI
41	Ishikawa T: Genetic polymorphism in the NRF2 gene as a prognosis marker for cancer chemotherapy. Front Genet. 5:3832014. View Article : Google Scholar : PubMed/NCBI
42	Nuydens R, Dispersyn G, Van Den Keiboom G, de Jong M, Connors R, Ramaekers F, Borgers M and Geerts H: Bcl-2 protects against apoptosis-related microtubule alterations in neuronal cells. Apoptosis. 5:43–51. 2000. View Article : Google Scholar : PubMed/NCBI
43	Anedda A, López-Bernardo E, Acosta-Iborra B, Suleiman Saadeh M, Landázuri MO and Cadenas S: The transcription factor Nrf2 promotes survival by enhancing the expression of uncoupling protein 3 under conditions of oxidative stress. Free Radic Biol Med. 61:395–407. 2013. View Article : Google Scholar : PubMed/NCBI
44	Jeong YH, Park JS, Kim DH and Kim HS: Lonchocarpine increases Nrf2/ARE-mediated antioxidant enzyme expression by modulating AMPK and MAPK signaling in brain astrocytes. Biomol Ther (Seoul). 24:581–588. 2016. View Article : Google Scholar : PubMed/NCBI
45	Birben E, Sahiner UM, Sackesen C, Erzurum S and Kalayci O: Oxidative stress and antioxidant defense. World Allergy Organ J. 5:9–19. 2012. View Article : Google Scholar : PubMed/NCBI