Volume 28, Issue 2 (July 2024)                   Physiol Pharmacol 2024, 28(2): 206-218 | Back to browse issues page

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Maleklou M, Abnosi M H. High concentration of nitric oxide impaired proliferation of bone marrow mesenchymal stem cells due to cell cycle arrest at G1 stage. Physiol Pharmacol 2024; 28 (2) : 10
URL: http://ppj.phypha.ir/article-1-2089-en.html
Abstract:   (652 Views)

Introduction: Although exogenous nitric oxide (NO) is used as medicine, in the previous we showed its inhibitory effect on the proliferation ability of rat bone marrow mesenchymal stem cells (BMSCs). In the present investigation, the inhibitory role of exogenous NO on BMSCs cell cycle was studied.
Methods: BMSCs after the third passage were treated for one hour every 48 hours with 100μM of sodium nitroprusside as an NO donor. Then, after 5,10,15, and 20 days of treatment, the viability, proliferation, and cell cycle of the BMSCs was investigated. In addition, the expression of the Raf1, CDK2, CDK4, P53, and GAPDH genes was studied.
Results: Cell treatment caused a significant reduction in viability and proliferation at 5,10,15, and 20 days. Also, the treatment caused cell cycle arrest at G1 after 20 days. In addition, it was found that the CDK2 and CDK4 expression were down-regulated whereas the P53 expression was up-regulated, but the expression of Raf1 as well as GAPDH remained the same.
Conclusion: This study showed that prolonged treatment with a NO donor arrest the BMSCs cell cycle due to overexpression of P53, which inhibits the expression of Cdk2 and Cdk4.

Article number: 10
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1. Abnosi M H, Masoomi S. Para-nonylphenol toxicity induces oxidative stress and arrests the cell cycle in mesenchymal stem cells of bone marrow. Iranian Journal of Toxicology 2019;13 (3): 1-8. [DOI:10.32598/IJT.13.3.496.2]
2. Abnosi M H, Masoomi S. p-Nonylphenol impairment of osteogenic differentiation of mesenchymal stem cells was found to be due to oxidative stress and down-regulation of RUNX2 and BMP. Endocrine, Metabolic & Immune Disorders - Drug Targets. 2020; 20: 1336-1346. [DOI:10.2174/1871530320666200505114058]
3. Abnosi M H, Pari S. Exogenous nitric oxide induced early mineralization in rat bone marrow mesenchymal stem cells via activation of alkaline phosphatase. Iranian Biomedical Journal. 2019; 23 (2): 142-152. [DOI:10.29252/.23.2.142]
4. Abnosi M H, Sargolzaei I D J, Maleklou M. Exogenous nitric oxide up-regulates the runx2 via bmp7 overexpression to increase the osteoblast matrix production in vitro. Avicenna Journal of Medical Biochemistry 2022; 10(1): 58-64.
5. Abnosi M H, Yari S. The toxic effect of gallic acid on biochemical factors, viability and proliferation of rat bone marrow mesenchymal stem cells was compensated. by boric acid. Journal of Trace Elements in Medicine and Biology. 2018; 48: 246-253. [DOI:10.1016/j.jtemb.2018.04.016]
6. Fok H, Jiang B, Clapp B, Chowienczyk P. Regulation of vascular tone and pulse wave velocity in human muscular conduit arteries: selective effects of nitric oxide donors to dilate muscular arteries relative to resistance vessels. Hypertension. 2012; 60(5): 1220-5. [DOI:10.1161/hypertensionaha.112.198788]
7. Chu L, Jiang Y, Hao H, Xia Y, Xu J, Liu Z, et al. Nitric oxide enhances Oct-4 expression in bone marrow stem cells and promotes endothelial differentiation. European Journal of Pharmacology 2008; 591(1-3): 59-65. [DOI:10.1016/j.ejphar.2008.06.066]
8. Coller H A, Sang L, Roberts J M. A new description of cellular quiescence. PLOS Biology 2006; 4: e83. [DOI:10.1371/journal.pbio.0040083]
9. Darzynkiewicz Z, Juan G. DNA content measurement for DNA ploidy and cell cycle analysis. Current Protocols in Cytometry 1997; 00(1): 7.5.1–7.5.24. [DOI:10.1002/0471142956.cy0705s00]
10. Ding L, Cao G, Lin W, Chen H, Xiong X, Ao H, Yu M, Lin J, Cui. The roles of cyclin-dependent kinases in cell-cycle progression and therapeutic strategies in human breast cancer. International Molecular Science. 2020; 21(6): 1960. [DOI:10.3390/ijms21061960]
11. Dong P, Maddali M V, Srimani J K, Thelt F, Nevins J R, Mathey-Prevot B, You L. Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control. Nature Communications 2014; 5:4750. [DOI:10.1038/ncomms5750]
12. Engeland K. Cell cycle regulation: p53-p21-RB signaling. Cell Death & Differentiation 2022; 29: 946–960. [DOI:10.1038/s41418-022-00988-z]
13. García-Aranda M I, Gonzalez-Padilla J E, Gómez-Castro C Z, Gómez-Gómez Y M, Rosales- Hernández M C, et al. Anti-inflammatory effect and inhibition of nitric oxide production by targeting COXs and iNOS enzymes with the 1,2-diphenylbenzimidazole pharmacophore. Bioorganic & Medicinal Chemistry. 2020; 28(9): 115427. [DOI:10.1016/j.bmc.2020.115427]
14. Hill BG, Dranka BP, Bailey S M, Lancaster J R Jr, Darley-Usmar V M. What part of NO don’t you understand? Some answers to the cardinal questions in nitric oxide biology. Journal of Biological Chemistry 2010; 285(26): 19699-19704. [DOI:10.1074/jbc.r110.101618]
15. Hinrichsen R Hansen, A H, Haunsø S, Busk P K. Phosphorylation of pRb by cyclin D kinase is necessary for development of cardiac hypertrophy. Cell Proliferation 2008; 41(5): 813-829. [DOI:10.1111/j.1365-2184.2008.00549.x]
16. Hottinger D G, Beebe D S, Kozhimannil T, Prielipp R C, Belani K G. Sodium nitroprusside in 2014: A clinical concepts review. Journal of Anaesthesiology Clinical Pharmacology 2014; 30(4): 462-71. [DOI:10.4103/0970-9185.142799]
17. Hume S, Dianov GL, Ramadan K. A unified model for the G1/S cell cycle transition. Nucleic Acids Research 2020; 48(22): 12483–12501. [DOI:10.1093/nar/gkaa1002]
18. Mohammadi A, Abnosi M H, Pakyari R. Low concentration of sodium nitroprusside promotes mesenchymal stem cell viability and proliferation through elevation of metabolic activity. Avicenna Journal of Medical Biochemistry. 2017;5(1):9-16. [DOI:10.15171/ajmb.2017.02]
19. Oleson B J, Corbett J A. Dual role of nitric oxide in regulating the response of β cells to DNA damage. Antioxidants & Redox Signaling 2018; 29(14):1432-1445. [DOI:10.1089/ars.2017.7351]
20. Pack L R, Daigh L H, Chung M, Meyer T. Clinical CDK4/6 inhibitors induce selective and immediate dissociation of p21 from cyclin D-CDK4 to inhibit CDK2. Nature Communications 2021; 12: 3356. [DOI:10.1038/s41467-021-23612-z]
21. Pari S, Abnosi M H, Pakyari R. Sodium nitroprusside changed the metabolism of mesenchymal stem cells to an anaerobic state while viability and proliferation remained intact. Cell Journal (Yakhteh). 2017; 19(1): 146-158. [DOI:10.22074/cellj.2016.4875]
22. Ren G, Zhang L, Zhao X, Xu G, Zhang Y, Roberts A I, Zhao R C, Shi Y. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell 2008; 7;2(2):141-50. [DOI:10.1016/j.stem.2007.11.014.]
23. Takagi K, Isobe Y, Yasukawa K, Okouchi E, Suketa Y. Nitric oxide blocks the cell cycle of mouse macrophage-like cells in the early G2+ M phase. FEBS Letters 1994; 340(3): 159-162. [DOI:10.1016/0014-5793(94)80128-2]
24. Thomas D D, Ridnour L A, Isenberg J S, et al. The chemical biology of nitric oxide: implications in cellular signaling. Free Radical Biology and Medicine 2008; 45:18-31. [DOI:10.1016/j.freeradbiomed.2008.03.020]
25. Vermeulen K, Van Bockstaele D R, Berneman ZN. The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Proliferation 2003; 36(3):131-149. [DOI:10.1046/j.1365-2184.2003.00266.x]
26. Villalobo A. Nitric oxide and cell proliferation. The FEBS Journal 2006; 273(11): 2329-2344. [DOI:10.1111/j.1742-4658.2006.05250.x]
27. Wimalawansa S J. Nitric oxide: novel therapy for osteoporosis. Expert Opinion on Pharmacotherapy 2008; 9(17): 3025-3044. [DOI:10.1517/14656560802197162]
28. Wood J, Garthwaite J. Models of the diffusional spread of nitric oxide: implications for neural nitric oxide signaling and its pharmacological properties. Neuropharmacology 1994; 33(11): 1235-1244. [DOI:10.1016/0028-3908(94)90022-1]
29. Zhou Z, Hossain M S, Liu D. Involvement of the long noncoding RNA H19 in osteogenic differentiation and bone regeneration. Stem Cell Research & Therapy 2021; 12(1):74. [DOI:10.1186/s13287-021-02149-4]

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