Over-expression of survivin could prevent the oxidative stress and toxicity of rotenone in SH-SY5Y cells

Document Type : Original Article

Authors

1 Department of Molecular Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

2 Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

3 Department of Anatomical Sciences, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

4 Liver and Digestive Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran

5 Department of Pathology, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran

Abstract

Objective(s): It is important to find novel therapeutic molecular targets for curing Parkinson’s disease (PD). Accordingly, this study aimed to evaluate the effect of over-expression of the survivin gene, a gene frequently reported as neuroprotective, on the in vitro model of PD. 
Materials and Methods: Survivin was over-expressed in SH-SY5Y cells. Next, the cells were treated with rotenone (500 nM) for 24 hr. Then, viability and the total antioxidant capacity were assessed. The expression levels of 15 important genes of key cellular processes (oxidative stress, apoptosis, cell cycle, and autophagy) were assessed. The studied genes included survivin, superoxide dismutase, catalase, BAX, bcl2, caspase 3, caspase 8, caspase 9, p53, SMAC, β-catenin, mTOR, AMPK, ATG7, RPS18. The apoptosis level and the frequency of cell cycle stages were assessed by flow cytometry. For analyzing the data, the ANOVA test followed by Tukey’s test was used to evaluate the significant differences between the experimental groups. P<0.05 was considered significant. 
Results: Survivin could significantly decrease the rotenone-induced apoptosis in SH-SY5Y cells. The rotenone treatment led to down-regulation of catalase and up-regulation of bax, bcl2, caspase 3, caspase 8, P53, β-catenin, and ATG7. Survivin could significantly neutralize the effect of rotenone in most the genes. It could also increase the total antioxidant capacity of SH-SY5Y cells. 
Conclusion: Survivin could prevent the toxic effect of rotenone on SH-SY5Y cells during the development of in vitro PD model via regulating the genes of key cellular processes, including anti-oxidation, apoptosis, cell cycle, and autophagy. 

Keywords

References

1. Jankovic J. Parkinson’s disease: clinical features and diagnosis. J Neurol Neurosurg Psychiatry 2008; 79: 368-376. 
2. Vos T, Allen C, Arora M, Barber RM, Bhutta ZA, Brown A, et al. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990–2015: A systematic analysis for the global burden of disease study 2015. The Lancet 2016; 388: 1545-1602. 
3. Thomas B, Beal MF. Molecular insights into parkinson’s disease. F1000 Med Rep 2011; 3: 7-15. 
4. Hassanzadeh K, Rahimmi A. Oxidative stress and neuroinflammation in the story of parkinson’s disease: could targeting these pathways write a good ending? J Cell Physiol 2018; 234: 23-32. 
5. Hu X, Song Q, Li X, Li D, Zhang Q, Meng W, et al. Neuroprotective effects of kukoamine A on neurotoxin-induced parkinson’s model through apoptosis inhibition and autophagy enhancement. Neuropharmacology 2017; 117: 352-363. 
6. Cossu F, Milani M, Mastrangelo E, Lecis D. Targeting the BIR domains of inhibitor of apoptosis (IAP) proteins in cancer treatment. Comput Struct Biotechnol J 2019; 17: 142-150. 
7. Baratchi S, Kanwar RK, Kanwar JR. Survivin: a target from brain cancer to neurodegenerative disease. Crit Rev Biochem Mol Biol 2010; 45: 535-554. 
8. Chen X, Duan N, Zhang C, Zhang W. Survivin and tumorigenesis: molecular mechanisms and therapeutic strategies. J Cancer 2016; 7: 314-323. 
9. Jia L, Piña-Crespo J, Li Y. Restoring Wnt/β-catenin signaling is a promising therapeutic strategy for alzheimer’s disease. Mol Brain 2019; 12: 1-11. 
10. Tolosa L, Mir M, Asensio VJ, Olmos G, Lladó J. Vascular endothelial growth factor protects spinal cord motoneurons against glutamate‐induced excitotoxicity via phosphatidylinositol 3‐kinase. J Neurochem 2008; 105: 1080-1090. 
11. Zhang Q-G, Wang R, Khan M, Mahesh V, Brann DW. Role of dickkopf-1, an antagonist of the Wnt/β-catenin signaling pathway, in estrogen-induced neuroprotection and attenuation of tau phosphorylation. J Neurosci 2008; 28: 8430-8441. 
12. Chu S-F, Zhang Z, Zhang W, Zhang M-J, Gao Y, Han N, et al. Upregulating the expression of survivin-HBXIP complex contributes to the protective role of IMM-H004 in transient global cerebral ischemia/reperfusion. Mol Neurobiol 2017; 54: 524-540. 
13. Sehara Y, Sawicka K, Hwang J-Y, Latuszek-Barrantes A, Etgen AM, Zukin RSJJoN. Survivin is a transcriptional target of STAT3 critical to estradiol neuroprotection in global ischemia. J Neurosci 2013; 33: 12364-12374. 
14. Baratchi S, Kanwar RK, Kanwar JR. Survivin mutant protects differentiated dopaminergic SK-N-SH cells against oxidative stress. PLoS One 2011; 6: 15865-15873. 
15. Syahrani RA, Yunita E, Wanandi SI. Suppression of rotenone-treated human breast cancer stem cell survival using survivin inhibitor YM155 is associated to oxidative stress modulation. Asian Pac J Cancer Prev 2020; 21: 2631-2637. 
16. Roca H, Varsos ZS, Mizutani K, Pienta KJ. CCL2, survivin and autophagy: new links with implications in human cancer. Autophagy 2008; 4: 969-971. 
17. Kwee JK, Luque DG, dos Santos Ferreira AC, da Cunha Vasconcelos F, Silva KL, Klumb CE, et al. Modulation of reactive oxygen species by anti-oxidants in chronic myeloid leukemia cells enhances imatinib sensitivity through survivin downregulation. Anticancer Drugs 2008; 19: 975-981.
18. Tang C, Lu Y-H, Xie J-H, Wang F, Zou J-N, Yang J-S, et al. Downregulation of survivin and activation of caspase-3 through the PI3K/Akt pathway in ursolic acid-induced HepG2 cell apoptosis. Anticancer Drugs 2009; 20: 249-258. 
19. Eslami F, Mahdavi M, Babaei E, Hussen BM, Mostafavi H, Shahbazi A, et al. Down-regulation of survivin and Bcl-2 concomitant with the activation of caspase-3 as a mechanism of apoptotic death in KG1a and K562 cells upon exposure to a derivative from ciprofloxacin family. Toxicol Appl Pharmacol 2020; 409: 115331-115343. 
20. Wang M-J, Huang H-Y, Chiu T-L, Chang H-F, Wu H-R. Peroxiredoxin 5 silencing sensitizes dopaminergic neuronal cells to rotenone via DNA damage-triggered ATM/p53/PUMA signaling-mediated apoptosis. Cells 2020; 9: 22-47. 
21.Raimundo LSG. Drugging p53 in cancer: From yeast to human cells. 2014. 
22. Lukin DJ. Cell cycle regulation by the tumor suppressor p53: Mount Sinai School of Medicine of New York University; 2006. 
23. Hafner A, Bulyk ML, Jambhekar A, Lahav G. The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol 2019; 20: 199-210. 
24. Marchetti B. Wnt/β-catenin signaling pathway governs a full program for dopaminergic neuron survival, neurorescue and regeneration in the MPTP mouse model of parkinson’s disease. Int J Mol Sci 2018; 19: 3743-3771. 
25. Ou D-L, Lee B-S, Lin L-I, Liou J-Y, Liao S-C, Hsu C, et al. Vertical blockade of the IGFR- PI3K/Akt/mTOR pathway for the treatment of hepatocellular carcinoma: The role of survivin. Mol Cancer 2014; 13:2-13. 
26. Vaira V, Lee CW, Goel HL, Bosari S, Languino LR, Altieri DC. Regulation of survivin expression by IGF-1/mTOR signaling. Oncogene 2007; 26: 2678-2684. 
27. Lin TY, Chan HH, Chen SH, Sarvagalla S, Chen PS, Coumar MS, et al. BIRC5/Survivin is a novel ATG12–ATG5 conjugate interactor and an autophagy-induced DNA damage suppressor in human cancer and mouse embryonic fibroblast cells. Autophagy 2020; 16: 1296-1313.
Iranian Journal of Basic Medical Sciences
Volume 25, Issue 7
July 2022
Pages 842-849

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