Volume 26, Issue 1 (March 2022)                   Physiol Pharmacol 2022, 26(1): 79-87 | Back to browse issues page

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Abdanipour A, Amalavar M, Alipour M, Feizi H. Selegiline induces adipose tissue-derived stem cells into neuron-like cells through MAPK signaling pathway. Physiol Pharmacol. 2022; 26 (1) :79-87
URL: http://ppj.phypha.ir/article-1-1710-en.html
Abstract:   (693 Views)
Introduction: Adipose-derived stem cells (ADSCs) are one of the most well-known and accessible sources of stem cells that can be used for the treatment of neurodegenerative diseases. On the other hand, previous studies have suggested that selegiline, as an irreversible inhibitor of monoamine oxidase, affects stem cells’ differentiation into neurons. This study was conducted to investigate the involvement in phosphatidylinositol-bisphosphate 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways in ADSCs differentiation to neuron-like cells using selegiline as inducer. Methods: ADSCs were isolated from male rats, cultured in DMEM and then treated with selegiline (10-7 M) for 24h. Real-time PCR for nestin and neurofilament-68 (NF-68) was performed from the negative control (ADSCs at the 3rd passage), positive control (ADSCs were treated with 10-7 M selegeline for 24h, PI3AKT inhibitor (ADSCs were pretreated with treated with 10µM LY294002 for 3h, then10-7 M selegeline for the next 24h, and MAPK inhibitor (ADSCs were pretreated with treated with 10µM PD98059 for 3h, then10-7 M selegeline for the next 24h). Results: Nestin and NF-68 genes have been over-expressed in the selegiline-treated ADSCs. The PD98059 and LY294002 significantly down-regulated the selegiline-induced over-expression of nestin and NF-68; however, PI3K inhibition did not return the genes expression to control level. ADSCs were immunoreactivefor nestin and NF-68 about 98% and 95% respectively. Conclusion: According to the results, selegilinecan induce the gene expression of neural stem cell biomarkers in ADSCs through MAPK pathway activating and so differentiating them into neuron-like cells.
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1. Abdanipour A, Jafari Anarkooli I, Shokri S, Ghorbanlou M, Bayati V, Nejatbakhsh R. Neuroprotective effects of selegiline on rat neural stem cells treated with hydrogen peroxide. Biomed Rep 2018; 8: 41-6. [DOI:10.3892/br.2017.1023]
2. Abdanipour A, Tiraihi T, Delshad A. Trans-differentiation of the adipose tissue-derived stem cells into neuron-like cells expressing neurotrophins by selegiline. Iran Biomed J 2011; 15: 113.
3. Abdanipour A, Tiraihi T. Induction of adipose-derived stem cell into motoneuron-like cells using selegiline as preinducer. Brain Res 2012; 1440: 23-33. [DOI:10.1016/j.brainres.2011.12.051]
4. Alhadlaq A, Mao JJ. Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev 2004; 13: 436-48. [DOI:10.1089/scd.2004.13.436]
5. Am OB, Amit T, Youdim M B. Contrasting neuroprotective and neurotoxic actions of respective metabolites of anti-Parkinson drugs rasagiline and selegiline. Neurosci Lett 2004; 355: 169-72. [DOI:10.1016/j.neulet.2003.10.067]
6. Amura CR, Marek L, Winn RA, Heasley LE. Inhibited neurogenesis in JNK1-deficient embryonic stem cells. Mol Cell Biol 2005; 25: 10791-802. [DOI:10.1128/MCB.25.24.10791-10802.2005]
7. Andoh T, Chock PB, Murphy DL, Chiueh C. Role of the redox protein thioredoxin in cytoprotective mechanism evoked by (-)-deprenyl. Mol Pharmacol 2005; 68: 1408-14. [DOI:10.1124/mol.105.012302]
8. Bai WF, Zhang Y, Xu W, Li W, Li M, Yuan F, et al. Isolation and characterization of neural progenitor cells from bone marrow in cell replacement therapy of brain injury. Front Cell Neurosci 2020; 14: 49. [DOI:10.3389/fncel.2020.00049]
9. Boulland JL, Mastrangelopoulou M, Boquest AC, Jakobsen R, Noer A, Glover JC, et al. Epigenetic regulation of nestin expression during neurogenic differentiation of adipose tissue stem cells. Stem Cells Dev 2013; 22: 1042-52. [DOI:10.1089/scd.2012.0560]
10. Cardozo AJ, Gomez DE, Argibay PF. Neurogenic differentiation of human adipose-derived stem cells: relevance of different signaling molecules, transcription factors, and key marker genes. Gene 2012; 511: 427-36. [DOI:10.1016/j.gene.2012.09.038]
11. Creson TK, Yuan P, Manji HK, Chen G. Evidence for involvement of ERK, PI3K, and RSK in induction of Bcl-2 by valproate. J Mol Neurosci 2009; 37: 123-34. [DOI:10.1007/s12031-008-9122-2]
12. Debnath T, Chelluri LK. Standardization and quality assessment for clinical grade mesenchymal stem cells from human adipose tissue. Hematol Transfus Cell Ther 2019; 41: 7-16. [DOI:10.1016/j.htct.2018.05.001]
13. Dinsmore CJ, Soriano P. MAPK and PI3K signaling: At the crossroads of neural crest development. Dev Biol 2018; 444: S79-97. [DOI:10.1016/j.ydbio.2018.02.003]
14. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy 2006; 8: 315-7. [DOI:10.1080/14653240600855905]
15. Esmaeili F, Tiraihi T, Movahedin M, Mowla SJ. Selegiline induces neuronal phenotype and neurotrophins expression in embryonic stem cells. Rejuvenation Res 2006; 9: 475-84. [DOI:10.1089/rej.2006.9.475]
16. Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci 2020; 77: 2771-94. [DOI:10.1007/s00018-020-03454-6]
17. Fraser JK, Wulur I, Alfonso Z, Hedrick MH. Fat tissue: an underappreciated source of stem cells for biotechnology. Trends Biotechnol 2006; 24: 150-4. [DOI:10.1016/j.tibtech.2006.01.010]
18. Hong L, Peptan IA, Colpan A, Daw JL. Adipose tissue engineering by human adipose-derived stromal cells. Cells Tissues Organs 2006; 183: 133-40. [DOI:10.1159/000095987]
19. Huang T, He D, Kleiner G, Kuluz J. Neuron-like differentiation of adipose-derived stem cells from infant piglets in vitro. J Spinal Cord Med 2007; 30: S35-40. [DOI:10.1080/10790268.2007.11753967]
20. Huang W, Zhao Y, Zhu X, Cai Z, Wang S, Yao S, et al. Fluoxetine upregulates phosphorylatedAKT and phosphorylated-ERK1/2 proteins in neural stem cells: evidence for a crosstalk between AKT and ERK1/2 pathways. J Mol Neurosci 2013; 49: 244-9. [DOI:10.1007/s12031-012-9822- 5]
21. Isele NB, Lee HS, Landshamer S, Straube A, Padovan CS, Plesnila N, et al. Bone marrow stromal cells mediate protection through stimulation of PI3-K/Akt and MAPK signaling in neurons. Neurochem Int 2007; 50: 243-50. [DOI:10.1016/j.neuint.2006.08.007]
22. Kingham PJ, Kalbermatten DF, Mahay D, Armstrong SJ, Wiberg M, Terenghi G. Adiposederived stem cells differentiate into a Schwann cell phenotype and promote neurite outgrowth in vitro. Exp Neurol 2007; 207: 267-74. [DOI:10.1016/j.expneurol.2007.06.029]
23. Magyar K, Szende B. (-)-Deprenyl, a selective MAO-B inhibitor, with apoptotic and antiapoptotic properties. Neurotoxicology 2004; 25: 233-42. [DOI:10.1016/S0161-813X(03)00102-5]
24. Mizuno H. Adipose-derived stem cells for tissue repair and regeneration: ten years of research and a literature review. J Nippon Med Sch 2009; 76: 56-66. [DOI:10.1272/jnms.76.56]
25. Mizuta I, Ohta M, Ohta K, Nishimura M, Mizuta E, Hayashi K, et al. Selegiline and desmethylselegiline stimulate NGF, BDNF, and GDNF synthesis in cultured mouse astrocytes. Biochem Biophys Res Commun 2000; 279: 751-5. [DOI:10.1006/bbrc.2000.4037]
26. Modrak M, Talukder M A H, Gurgenashvili K, Noble M, Elfar J C. Peripheral nerve injury and myelination: Potential therapeutic strategies. J Neurosci Res 2020; 98: 780-95. [DOI:10.1002/jnr.24538]
27. Moelling K, Schad K, Bosse M, Zimmermann S, Schweneker M. Regulation of Raf-Akt Crosstalk. J Biol Chem 2002; 277: 31099-106. [DOI:10.1074/jbc.M111974200]
28. Nakaso K, Nakamura C, Sato H, Imamura K, Takeshima T, Nakashima K. Novel cytoprotective mechanism of anti-parkinsonian drug deprenyl: PI3K and Nrf2-derived induction of antioxidative proteins. Biochem Biophys Res Commun 2006; 339: 915-22. [DOI:10.1016/j.bbrc.2005.11.095]
29. Naoi M, Maruyama W, Shamoto-Nagai M J J o N T. Rasagiline and selegiline modulate mitochondrial homeostasis, intervene apoptosis system and mitigate α-synuclein cytotoxicity in disease-modifying therapy for Parkinson's disease. J Neural Transm (Vienna). 2020; 127: 131- 47. [DOI:10.1007/s00702-020-02150-w]
30. Pearson G, Robinson F, Beers Gibson T, Xu B E, Karandikar M, Berman K, et al. Mitogenactivated protein (MAP) kinase pathways: regulation and physiological functions. Endocr Rev 2001; 22: 153-83. [DOI:10.1210/edrv.22.2.0428]
31. Shan Z Y, Shen J L, Li Q M, Wang Y, Huang X Y, Guo T Y, et al. pCREB is involved in neural induction of mouse embryonic stem cells by RA. Anat Rec (Hoboken) 2008; 291: 519-26. [DOI:10.1002/ar.20686]
32. Sylvester K G, Longaker M T. Stem cells: review and update. Arch Surg 2004; 139: 93-9. [DOI:10.1001/archsurg.139.1.93]
33. Taheri F, Kashani M, Ghorbanian M, Hosseinpour L. Inductive effect of Deprenyl and Dimethyl sulfoxide on proliferation and survival of the mesenchymal stem cells. J Gorgan Univ Med Sci. 2012; 14: 10-18.
34. Wang J, Chen Y, Yang Y, Xiao X, Chen S, Zhang C, et al. Endothelial progenitor cells and neural progenitor cells synergistically protect cerebral endothelial cells from Hypoxia/reoxygenation-induced injury via activating the PI3K/Akt pathway. Mol Brain 2016; 9: 12. [DOI:10.1186/s13041-016-0193-7]
35. Wang X. Stem cells in tissues, organoids, and cancers. Cell Mol Life Sci 2019; 76: 4043-70. [DOI:10.1007/s00018-019-03199-x]
36. Wei L, Wei Z Z, Jiang M Q, Mohamad O, Yu S P. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke. Prog Neurobiol 2017; 157: 49-78. [DOI:10.1016/j.pneurobio.2017.03.003]
37. Weinreb O, Amit T, Bar-Am O, Sagi Y, Mandel S, Youdim M. Involvement of multiple survival signal transduction pathways in the neuroprotective, neurorescue and APP processing activity of rasagiline and its propargyl moiety. in, Parkinson's Disease and Related Disorders (Springer). 2006; 70: 457-65 [DOI:10.1007/978-3-211-45295- 0_69]
38. Yuan J, Huang G, Xiao Z, Lin L, Han T J M, biochemistry c. Overexpression of β-NGF promotes differentiation of bone marrow mesenchymal stem cells into neurons through regulation of AKT and MAPK pathway. Mol Cell Biochem 2013; 383: 201-11. [DOI:10.1007/s11010-013-1768-6]

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