Prostaglandin E1 protects bone marrow‑derived mesenchymal stem cells against serum deprivation‑induced apoptosis

Zeng,Kuan; Deng,Bao Ping; Jiang,Hui‑Qi; Wang,Meng; Hua,Ping; Zhang,Hong‑Wu; Deng,Yu‑Bin; Yang,Yan‑Qi

doi:10.3892/mmr.2015.4176

Prostaglandin E1 protects bone marrow‑derived mesenchymal stem cells against serum deprivation‑induced apoptosis

Authors:
- Kuan Zeng
- Bao Ping Deng
- Hui‑Qi Jiang
- Meng Wang
- Ping Hua
- Hong‑Wu Zhang
- Yu‑Bin Deng
- Yan‑Qi Yang
View Affiliations

Affiliations: Department of Cardiac Surgery, Sun Yat‑sen Memorial Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China, Research Center of Translational Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China
Published online on: August 5, 2015 https://doi.org/10.3892/mmr.2015.4176
Pages: 5723-5729
Copyright: © Zeng et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mesenchymal stem cells (MSCs) have become a recent focus of experimental and clinical research regarding myocardial regeneration. However, the therapeutic potential of these cells is limited by poor survival. Prostaglandin E1 (PGE1) is known to have anti‑inflammatory and anti‑apoptotic effects on the myocardium. The aim of the present study was to determine whether PGE1 could protect MSCs against serum deprivation (SD)‑induced apoptosis. An SD model was used to induce apoptosis in MSCs in vitro. Apoptotic morphological changes were detected by Hoechst 33258 fluorescent nuclear staining; and Annexin V‑fluorescein isothiocyanate/propidium iodide (PI) double staining and flow cytometry was used to quantify the rate of apoptosis. Western blot analysis was used to detect the expression levels of the apoptosis‑associated proteins Bcl‑2, Bax and caspase‑3. The results of the present study demonstrated that SD induced apoptosis of MSCs, and that treatment with PGE1 attenuated the morphological changes characteristic of apoptosis. Annexin V/PI staining showed that the rate of apoptosis gradually increased with the duration of ischemia. Furthermore, treatment with PGE1 significantly reduced SD‑induced apoptosis, decreased the protein expression levels of Bax and caspase‑3, and increased the expression levels of Bcl‑2. These data suggest that PGE1 is able to influence the survival of MSCs under certain conditions. These results may aid in improving the therapeutic efficacy of MSC transplantation used to treat chronic ischemic heart disease.

View Figures

View References

1	Yu Q, Fan W and Cao F: Mechanistic molecular imaging of cardiac cell therapy for ischemic heart disease. Am J Physiol Heart Circ Physiol. 305:H947–H959. 2013. View Article : Google Scholar : PubMed/NCBI
2	Toyoda Y, Guy TS and Kashem A: Present status and future perspectives of heart transplantation. Circ J. 77:1097–1110. 2013. View Article : Google Scholar : PubMed/NCBI
3	Burchill LJ and Ross HJ: Heart transplantation in adults with end-stage congenital heart disease. Future Cardiol. 8:329–342. 2012. View Article : Google Scholar : PubMed/NCBI
4	Schächinger V, Erbs S, Elsässer A, et al: Improved clinical outcome after intracoronary administration of bone-marrow-derived progenitor cells in acute myocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 27:2775–2783. 2006. View Article : Google Scholar : PubMed/NCBI
5	Tse HF, Thambar S, Kwong YL, et al: Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). Eur Heart J. 28:2998–3005. 2007. View Article : Google Scholar : PubMed/NCBI
6	Strauer BE and Steinhoff G: 10 years of intracoronary and intra-myocardial bone marrow stem cell therapy of the heart: from the methodological origin to clinical practice. J Am Coll Cardiol. 58:1095–1104. 2011. View Article : Google Scholar : PubMed/NCBI
7	Tang YL, Tang Y, Zhang YC, Qian K, Shen L and Phillips MI: Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol. 46:1339–1350. 2005. View Article : Google Scholar : PubMed/NCBI
8	Menasché P: Current status and future prospects for cell transplantation to prevent congestive heart failure. Semin Thorac Cardiovasc Surg. 20:131–137. 2008. View Article : Google Scholar : PubMed/NCBI
9	Zhao XS, Pan W, Bekeredjian R and Shohet RV: Endogenous endothelin-1 is required for cardiomyocyte survival in vivo. Circulation. 114:830–837. 2006. View Article : Google Scholar : PubMed/NCBI
10	Fang WT, Li HJ and Zhou LS: Protective effects of prostaglandin E1 on human umbilical vein endothelial cell injury induced by hydrogen peroxide. Acta Pharmacol Sin. 31:485–492. 2010. View Article : Google Scholar : PubMed/NCBI
11	Takikawa M, Sumi Y, Tanaka Y, et al: Protective effect of pros-taglandin E₁ on radiation-induced proliferative inhibition and apoptosis in keratinocytes and healing of radiation-induced skin injury in rats. J Radiat Res. 53:385–394. 2012. View Article : Google Scholar
12	Li JH, Yang P, Li AL, Wang Y, Ke YN and Li XL: Cardioprotective effect of liposomal prostaglandin E1 on a porcine model of myocardial infarction reperfusion no-reflow. J Zhejiang Univ Sci B. 12:638–643. 2011. View Article : Google Scholar : PubMed/NCBI
13	Jia C, Dai C, Bu X, et al: Co-administration of prostaglandin E1 with somatostatin attenuates acute liver damage after massive hepatectomy in rats via inhibition of inflammatory responses, apoptosis and endoplasmic reticulum stress. Int J Mol Med. 31:416–422. 2013.
14	Zeng X, Yu SP, Taylor T, Ogle M and Wei L: Protective effect of apelin on cultured rat bone marrow mesenchymal stem cells against apoptosis. Stem Cell Res. 8:357–367. 2012. View Article : Google Scholar : PubMed/NCBI
15	Chauvier D, Lecoeur H, Langonné A, et al: Upstream control of apoptosis by caspase-2 in serum-deprived primary neurons. Apoptosis. 10:1243–1259. 2005. View Article : Google Scholar : PubMed/NCBI
16	Chalah A and Khosravi-Far R: The mitochondrial death pathway. Adv Exp Med Biol. 615:25–45. 2008. View Article : Google Scholar : PubMed/NCBI
17	Suen DF, Norris KL and Youle RJ: Mitochondrial dynamics and apoptosis. Genes Dev. 22:1577–1590. 2008. View Article : Google Scholar : PubMed/NCBI
18	Martinou JC and Youle RJ: Mitochondria in apoptosis: Bcl-2 family members and mitochondrial dynamics. Dev Cell. 21:92–101. 2011. View Article : Google Scholar : PubMed/NCBI
19	Gross A, McDonnell JM and Korsmeyer SJ: BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13:1899–1911. 1999. View Article : Google Scholar : PubMed/NCBI
20	Zhang X, Wang Y, Gao Y, et al: Maintenance of high proliferation and multipotent potential of human hair follicle-derived mesenchymal stem cells by growth factors. Int J Mol Med. 31:913–921. 2013.PubMed/NCBI
21	Ding DC, Shyu WC and Lin SZ: Mesenchymal stem cells. Cell Transplant. 20:5–14. 2011. View Article : Google Scholar : PubMed/NCBI
22	Hale SL, Dai W, Dow JS and Kloner RA: Mesenchymal stem cell administration at coronary artery reperfusion in the rat by two delivery routes: a quantitative assessment. Life Sci. 83:511–515. 2008. View Article : Google Scholar : PubMed/NCBI
23	Hodgetts SI, Beilharz MW, Scalzo AA and Grounds MD: Why do cultured transplanted myoblasts die in vivo? DNA quantification shows enhanced survival of donor male myoblasts in host mice depleted of CD4+ and CD8+ cells or Nk1.1+ cells. Cell Transplant. 9:489–502. 2000.PubMed/NCBI
24	Tang YL, Tang Y, Zhang YC, Qian K, Shen L and Phillips MI: Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol. 46:1339–1350. 2005. View Article : Google Scholar : PubMed/NCBI
25	Mingliang R, Bo Z and Zhengguo W: Stem cells for cardiac repair: status, mechanisms and new strategies. Stem Cells Int. 2011:3109282011. View Article : Google Scholar
26	Huang J, Zhang Z, Guo J, et al: Genetic modification of mesenchymal stem cells overexpressing CCR1 increases cell viability, migration, engraftment, and capillary density in the injured myocardium. Circ Res. 106:1753–1762. 2010. View Article : Google Scholar : PubMed/NCBI
27	Huang F, Zhu X, Hu XQ, et al: Mesenchymal stem cells modified with miR-126 release angiogenic factors and activate Notch ligand Delta-like-4, enhancing ischemic angiogenesis and cell survival. Int J Mol Med. 31:484–492. 2013.
28	Liu XB, Chen H, Chen HQ, et al: Angiopoietin-1 preconditioning enhances survival and functional recovery of mesenchymal stem cell transplantation. J Zhejiang Univ Sci B. 13:616–623. 2012. View Article : Google Scholar : PubMed/NCBI
29	Zhang Z, Li S, Cui M, et al: Rosuvastatin enhances the therapeutic efficacy of adipose-derived mesenchymal stem cells for myocardial infarction via PI3K/Akt and MEK/ERK pathways. Basic Res Cardiol. 108:3332013. View Article : Google Scholar : PubMed/NCBI
30	Dong Q, Yang Y, Song L, Qian H and Xu Z: Atorvastatin prevents mesenchymal stem cells from hypoxia and serum-free injury through activating AMP-activated protein kinase. Int J Cardiol. 153:311–316. 2011. View Article : Google Scholar
31	Huang CL, Wu YW, Wang SS, et al: Continuous intravenous infusion of prostaglandin E1 improves myocardial perfusion reserve in patients with ischemic heart disease assessed by positron emission tomography: a pilot study. Ann Nucl Med. 25:462–468. 2011. View Article : Google Scholar : PubMed/NCBI
32	Hara Y, Akamatsu Y, Maida K, et al: A new liver graft preparation method for uncontrolled non-heart-beating donors, combining short oxygenated warm perfusion and prostaglandin E1. J Surg Res. 184:1134–1142. 2013. View Article : Google Scholar : PubMed/NCBI
33	Ma XQ, Fu RF, Feng GQ, Wang ZJ, Ma SG and Weng SA: Hypoxia-reoxygenation-induced apoptosis in cultured neonatal rat cardiomyocyets and the protective effect of prostaglandin E. Clin Exp Pharmacol Physiol. 32:1124–1130. 2005. View Article : Google Scholar
34	Dietrich JB: Apoptosis and anti-apoptosis genes in the Bcl-2 family. Arch Physiol Biochem. 105:125–135. 1997.In French. View Article : Google Scholar : PubMed/NCBI
35	Renault TT, Teijido O, Antonsson B, Dejean LM and Manon S: Regulation of Bax mitochondrial localization by Bcl-2 and Bcl-x(L): keep your friends close but your enemies closer. Int J Biochem Cell Biol. 45:64–67. 2013. View Article : Google Scholar
36	Degli EM and Dive C: Mitochondrial membrane permeabilisation by Bax/Bak. Biochem Biophys Res Commun. 304:455–461. 2003. View Article : Google Scholar
37	Nemec KN and Khaled AR: Therapeutic modulation of apoptosis: targeting the BCL-2 family at the interface of the mitochondrial membrane. Yonsei Med J. 49:689–697. 2008. View Article : Google Scholar : PubMed/NCBI
38	Autret A and Martin SJ: Emerging role for members of the Bcl-2 family in mitochondrial morphogenesis. Mol Cell. 36:355–363. 2009. View Article : Google Scholar : PubMed/NCBI
39	Garcia-Saez AJ, Fuertes G, Suckale J and Salgado J: Permeabilization of the outer mitochondrial membrane by Bcl-2 proteins. Adv Exp Med Biol. 677:91–105. 2010. View Article : Google Scholar : PubMed/NCBI
40	Hockenbery D, Nuñez G, Milliman C, Schreiber RD and Korsmeyer SJ: Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death. Nature. 348:334–336. 1990. View Article : Google Scholar : PubMed/NCBI
41	Haeberlein SL: Mitochondrial function in apoptotic neuronal cell death. Neurochem Res. 29:521–530. 2004. View Article : Google Scholar : PubMed/NCBI
42	Mukhopadhyay A, Shishodia S, Suttles J, et al: Ectopic expression of protein-tyrosine kinase Bcr-Abl suppresses tumor necrosis factor (TNF)-induced NF-kappa B activation and IkappaBalpha phosphorylation. Relationship with down-regulation of TNF receptors. J Biol Chem. 277:30622–30628. 2002. View Article : Google Scholar : PubMed/NCBI
43	Tan KO, Fu NY, Sukumaran SK, et al: MAP-1 is a mitochondrial effector of Bax. Proc Natl Acad Sci USA. 102:14623–14628. 2005. View Article : Google Scholar : PubMed/NCBI
44	Oltvai ZN, Milliman CL and Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:609–619. 1993. View Article : Google Scholar : PubMed/NCBI
45	Heon Seo K, Ko HM, Kim HA, et al: Platelet-activating factor induces up-regulation of antiapoptotic factors in a melanoma cell line through nuclear factor-kappaB activation. Cancer Res. 66:4681–4686. 2006. View Article : Google Scholar : PubMed/NCBI
46	Lakhani SA, Masud A, Kuida K, et al: Caspases 3 and 7: key mediators of mitochondrial events of apoptosis. Science. 311:847–851. 2006. View Article : Google Scholar : PubMed/NCBI
47	Zhu W, Chen J, Cong X, Hu S and Chen X: Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Stem Cells. 24:416–425. 2006. View Article : Google Scholar
48	Liu HJ, Ma JW, Qiao ZY and Xu B: Study of molecular mechanism of Prostaglandin E1 in inhibiting coronary heart disease. Mol Biol Rep. 40:6701–6708. 2013. View Article : Google Scholar : PubMed/NCBI