Login Register Cart 0
Research Article

高葡萄糖影响培养的人间充质干细胞中雷帕霉素，二甲双胍和过氧化氢的细胞毒性潜力

卷 19, 期 9, 2019

页: [688 - 698] 页: 11

弟呕挨: 10.2174/1566524019666190722115842

价格: $65

摘要

背景：氧化应激和慢性高血糖症是2型糖尿病的两个主要副作用，影响所有类型的细胞，包括间充质干细胞（MSC）。 作为细胞疗法的选择，了解MSC的行为将为有效治疗提供关键信息。 方法：用各种浓度的葡萄糖，二甲双胍，雷帕霉素和过氧化氢处理胎盘间充质干细胞，以监测其活力和细胞周期分布。 通过MTT测定法检查细胞活力。 通过碘化丙锭染色研究细胞周期分布，并使用膜联蛋白V碘化丙锭染色和流式细胞术确定细胞凋亡。 通过蛋白质印迹评估Akt，P70S6K和AMPK的激活，评估潜在信号通路的参与程度。 结果：结果表明，高葡萄糖可增强细胞活力并降低二甲双胍的毒性潜力。 但是，过氧化氢和雷帕霉素的毒性加剧。 结论：我们的研究结果表明，在培养中存在雷帕霉素，二甲双胍和过氧化氢的情况下，高葡萄糖浓度对胎盘间充质干细胞的生存能力有重大影响。

关键词: 葡萄糖，雷帕霉素，二甲双胍，过氧化氢，间充质干细胞，细胞毒性潜能

« Previous Next »
[1]
Unnikrishnan R, Pradeepa R, Joshi SR, Mohan V. Type 2 Diabetes: Demystifying the Global Epidemic. Diabetes 2017; 66(6): 1432-42.
[http://dx.doi.org/10.2337/db16-0766] [PMID: 28533294]
[2]
Nishikawa T, Edelstein D, Brownlee M. The missing link: a single unifying mechanism for diabetic complications. Kidney Int Suppl 2000; 77: S26-30.
[http://dx.doi.org/10.1046/j.1523-1755.2000.07705.x] [PMID: 10997687]
[3]
Liemburg-Apers DC, Willems PH, Koopman WJ, Grefte S. Interactions between mitochondrial reactive oxygen species and cellular glucose metabolism. Arch Toxicol 2015; 89(8): 1209-26.
[http://dx.doi.org/10.1007/s00204-015-1520-y] [PMID: 26047665]
[4]
Bashan N, Kovsan J, Kachko I, Ovadia H, Rudich A. Positive and negative regulation of insulin signaling by reactive oxygen and nitrogen species. Physiol Rev 2009; 89(1): 27-71.
[http://dx.doi.org/10.1152/physrev.00014.2008] [PMID: 19126754]
[5]
Rehman K, Akash MSH. Mechanism of generation of oxidative stress and pathophysiology of type 2 diabetes mellitus: How are they interlinked? J Cell Biochem 2017; 118(11): 3577-85.
[http://dx.doi.org/10.1002/jcb.26097] [PMID: 28460155]
[6]
Volpe CMO, Villar-Delfino PH, Dos Anjos PMF, Nogueira-Machado JA. Cellular death, reactive oxygen species (ROS) and diabetic complications. Cell Death Dis 2018; 9(2): 119.
[http://dx.doi.org/10.1038/s41419-017-0135-z] [PMID: 29371661]
[7]
Pernicova I, Korbonits M. Metformin--mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol 2014; 10(3): 143-56.
[http://dx.doi.org/10.1038/nrendo.2013.256] [PMID: 24393785]
[8]
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577-85.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[9]
Inoki K, Kim J, Guan KL. AMPK and mTOR in cellular energy homeostasis and drug targets. Annu Rev Pharmacol Toxicol 2012; 52: 381-400.
[http://dx.doi.org/10.1146/annurev-pharmtox-010611-134537] [PMID: 22017684]
[10]
Saxton RA, Sabatini DM. mTOR Signaling in Growth, Metabolism, and Disease. Cell 2017; 168(6): 960-76.
[http://dx.doi.org/10.1016/j.cell.2017.02.004] [PMID: 28283069]
[11]
Eid AA, Ford BM, Bhandary B, et al. Mammalian target of rapamycin regulates Nox4-mediated podocyte depletion in diabetic renal injury. Diabetes 2013; 62(8): 2935-47.
[http://dx.doi.org/10.2337/db12-1504] [PMID: 23557706]
[12]
Farmer RE, Ford D, Forbes HJ, et al. Metformin and cancer in type 2 diabetes: a systematic review and comprehensive bias evaluation. Int J Epidemiol 2017; 46(2): 728-44.
[http://dx.doi.org/10.1093/ije/dyx046] [PMID: 28031313]
[13]
Vallianou NG, Evangelopoulos A, Kazazis C. Metformin and cancer. Rev Diabet Stud 2013; 10(4): 228-35.
[http://dx.doi.org/10.1900/RDS.2013.10.228] [PMID: 24841876]
[14]
Jiang Y, Jahagirdar BN, Reinhardt RL, et al. Pluripotency of mesenchymal stem cells derived from adult marrow. Nature 2002; 418(6893): 41-9.
[http://dx.doi.org/10.1038/nature00870] [PMID: 12077603]
[15]
da Silva Meirelles L, Chagastelles PC, Nardi NB. Mesenchymal stem cells reside in virtually all post-natal organs and tissues. J Cell Sci 2006; 119(Pt 11): 2204-13.
[http://dx.doi.org/10.1242/jcs.02932] [PMID: 16684817]
[16]
Isakson M, de Blacam C, Whelan D, McArdle A, Clover AJ. Mesenchymal Stem Cells and Cutaneous Wound Healing: Current Evidence and Future Potential. Stem Cells Int 2015; 2015831095
[http://dx.doi.org/10.1155/2015/831095] [PMID: 26106431]
[17]
Burova E, Borodkina A, Shatrova A, Nikolsky N. Sublethal oxidative stress induces the premature senescence of human mesenchymal stem cells derived from endometrium. Oxid Med Cell Longev 2013; 2013474931
[http://dx.doi.org/10.1155/2013/474931] [PMID: 24062878]
[18]
Brandl A, Meyer M, Bechmann V, Nerlich M, Angele P. Oxidative stress induces senescence in human mesenchymal stem cells. Exp Cell Res 2011; 317(11): 1541-7.
[http://dx.doi.org/10.1016/j.yexcr.2011.02.015] [PMID: 21376036]
[19]
Krishan A. Rapid flow cytofluorometric analysis of mammalian cell cycle by propidium iodide staining. J Cell Biol 1975; 66(1): 188-93.
[http://dx.doi.org/10.1083/jcb.66.1.188] [PMID: 49354]
[20]
Mir Mohammadrezaei F. Mohseni kouchesfehani H, Montazeri H, Gharghabi M, Ostad SN, Ghahremani MH. Signaling crosstalk of FHIT, CHK2 and p38 in etoposide induced growth inhibition in MCF-7 cells. Cell Signal 2013; 25(1): 126-32.
[http://dx.doi.org/10.1016/j.cellsig.2012.09.019] [PMID: 23000346]
[21]
Welinder C, Ekblad L. Coomassie staining as loading control in Western blot analysis. J Proteome Res 2011; 10(3): 1416-9.
[http://dx.doi.org/10.1021/pr1011476] [PMID: 21186791]
[22]
Jumabay M, Moon JH, Yeerna H, Boström KI. Effect of Diabetes Mellitus on Adipocyte-Derived Stem Cells in Rat. J Cell Physiol 2015; 230(11): 2821-8.
[http://dx.doi.org/10.1002/jcp.25012] [PMID: 25854185]
[23]
Deorosan B, Nauman EA. The role of glucose, serum, and three-dimensional cell culture on the metabolism of bone marrow-derived mesenchymal stem cells. Stem Cells Int 2011; 2011429187
[http://dx.doi.org/10.4061/2011/429187] [PMID: 21603146]
[24]
Weil BR, Abarbanell AM, Herrmann JL, Wang Y, Meldrum DR. High glucose concentration in cell culture medium does not acutely affect human mesenchymal stem cell growth factor production or proliferation. Am J Physiol Regul Integr Comp Physiol 2009; 296(6): R1735-43.
[http://dx.doi.org/10.1152/ajpregu.90876.2008] [PMID: 19386985]
[25]
Ryu JM, Lee MY, Yun SP, Han HJ. High glucose regulates cyclin D1/E of human mesenchymal stem cells through TGF-beta1 expression via Ca2+/PKC/MAPKs and PI3K/Akt/mTOR signal pathways. J Cell Physiol 2010; 224(1): 59-70.
[PMID: 20232305]
[26]
Cong LN, Chen H, Li Y, et al. Physiological role of Akt in insulin-stimulated translocation of GLUT4 in transfected rat adipose cells. Mol Endocrinol 1997; 11(13): 1881-90.
[http://dx.doi.org/10.1210/mend.11.13.0027] [PMID: 9415393]
[27]
Hers I, Vincent EE, Tavaré JM. Akt signalling in health and disease. Cell Signal 2011; 23(10): 1515-27.
[http://dx.doi.org/10.1016/j.cellsig.2011.05.004] [PMID: 21620960]
[28]
Grabiec K, Gajewska M, Milewska M, Błaszczyk M, Grzelkowska-Kowalczyk K. The influence of high glucose and high insulin on mechanisms controlling cell cycle progression and arrest in mouse C2C12 myoblasts: the comparison with IGF-I effect. J Endocrinol Invest 2014; 37(3): 233-45.
[http://dx.doi.org/10.1007/s40618-013-0007-z] [PMID: 24615360]
[29]
Wei ML, Duan P, Wang ZM, Ding M, Tu P. High glucose and high insulin conditions promote MCF7 cell proliferation and invasion by upregulating IRS1 and activating the Ras/Raf/ERK pathway. Mol Med Rep 2017; 16(5): 6690-6.
[http://dx.doi.org/10.3892/mmr.2017.7420] [PMID: 28901503]
[30]
Kuruganti PA, Wurster RD, Lucchesi PA. Mitogen activated protein kinase activation and oxidant signaling in astrocytoma cells. J Neurooncol 2002; 56(2): 109-17.
[http://dx.doi.org/10.1023/A:1014530309082] [PMID: 11995811]
[31]
Guo YL, Chakraborty S, Rajan SS, Wang R, Huang F. Effects of oxidative stress on mouse embryonic stem cell proliferation, apoptosis, senescence, and self-renewal. Stem Cells Dev 2010; 19(9): 1321-31.
[http://dx.doi.org/10.1089/scd.2009.0313] [PMID: 20092403]
[32]
Robertson RP. Chronic oxidative stress as a central mechanism for glucose toxicity in pancreatic islet beta cells in diabetes. J Biol Chem 2004; 279(41): 42351-4.
[http://dx.doi.org/10.1074/jbc.R400019200] [PMID: 15258147]
[33]
Hruda J, Sramek V, Leverve X. High glucose increases susceptibility to oxidative-stress-induced apoptosis and DNA damage in K-562 cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 2010; 154(4): 315-20.
[http://dx.doi.org/10.5507/bp.2010.047] [PMID: 21293542]
[34]
Soares HP, Ni Y, Kisfalvi K, Sinnett-Smith J, Rozengurt E. Different patterns of Akt and ERK feedback activation in response to rapamycin, active-site mTOR inhibitors and metformin in pancreatic cancer cells. PLoS One 2013; 8(2)e57289
[http://dx.doi.org/10.1371/journal.pone.0057289] [PMID: 23437362]
[35]
Morita M, Prudent J, Basu K, Goyon V, Katsumura S, Hulea L, et al. mTOR Controls Mitochondrial Dynamics and Cell Survival via MTFP1. Mol Cell 2017; 67(6): 922-35.e5.
[36]
Keats E, Khan ZA. Unique responses of stem cell-derived vascular endothelial and mesenchymal cells to high levels of glucose. PLoS One 2012; 7(6)e38752
[http://dx.doi.org/10.1371/journal.pone.0038752] [PMID: 22701703]
[37]
Silvestri A, Palumbo F, Rasi I, et al. Metformin induces apoptosis and downregulates pyruvate kinase M2 in breast cancer cells only when grown in nutrient-poor conditions. PLoS One 2015; 10(8)e0136250
[http://dx.doi.org/10.1371/journal.pone.0136250] [PMID: 26291325]
[38]
Habib SL, Kasinath BS, Arya RR, Vexler S, Velagapudi C. Novel mechanism of reducing tumourigenesis: upregulation of the DNA repair enzyme OGG1 by rapamycin-mediated AMPK activation and mTOR inhibition. Eur J Cancer 2010; 46(15): 2806-20.
[http://dx.doi.org/10.1016/j.ejca.2010.06.117] [PMID: 20656472]
[39]
Mukhopadhyay S, Saqcena M, Chatterjee A, Garcia A, Frias MA, Foster DA. Reciprocal regulation of AMP-activated protein kinase and phospholipase D. J Biol Chem 2015; 290(11): 6986-93.
[http://dx.doi.org/10.1074/jbc.M114.622571] [PMID: 25632961]
[40]
Fraenkel M, Ketzinel-Gilad M, Ariav Y, et al. mTOR inhibition by rapamycin prevents beta-cell adaptation to hyperglycemia and exacerbates the metabolic state in type 2 diabetes. Diabetes 2008; 57(4): 945-57.
[http://dx.doi.org/10.2337/db07-0922] [PMID: 18174523]

Rights & Permissions Print Cite
Article Metrics
31
4
1
1
© 2024 Bentham Science Publishers | Privacy Policy