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Apoptosis

, Volume 20, Issue 3, pp 273–284 | Cite as

Lysophosphatidic acid rescues bone mesenchymal stem cells from hydrogen peroxide-induced apoptosis

  • Xian-Yun Wang
  • Xue-Song Fan
  • Lin Cai
  • Si Liu
  • Xiang-Feng Cong
  • Xi ChenEmail author
Original Paper

Abstract

The increase of reactive oxygen species in infracted heart significantly reduces the survival of donor mesenchymal stem cells, thereby attenuating the therapeutic efficacy for myocardial infarction. In our previous study, we demonstrated that lysophosphatidic acid (LPA) protects bone marrow-derived mesenchymal stem cells (BMSCs) against hypoxia and serum deprivation-induced apoptosis. However, whether LPA protects BMSCs from H2O2-induced apoptosis was not examined. In this study, we report that H2O2 induces rat BMSC apoptosis whereas LPA pre-treatment effectively protects BMSCs from H2O2-induced apoptosis. LPA protection of BMSC from the induced apoptosis is mediated mostly through LPA3 receptor. Furthermore, we found that membrane G protein Gi2 and Gi3 are involved in LPA-elicited anti-apoptotic effects through activation of ERK1/2- and PI3 K-pathways. Additionally, H2O2 increases levels of type II of light chain 3B (LC3B II), an autophagy marker, and H2O2-induced autophagy thus protected BMSCs from apoptosis. LPA further increases the expression of LC3B II in the presence of H2O2. In contrast, autophagy flux inhibitor bafilomycin A1 has no effect on LPA’s protection of BMSC from H2O2-induced apoptosis. Taken together, our data suggest that LPA rescues H2O2-induced apoptosis mainly by interacting with Gi-coupled LPA3, resulting activation of the ERK1/2- and PI3 K/AKT-pathways and inhibition caspase-3 cleavage, and LPA protection of BMSCs against the apoptosis is independent of it induced autophagy.

Keywords

Bone marrow-mesenchymal stem cells (BMSCs) Lysophosphatidic acid (LPA) Hydrogen peroxide (H2O2Apoptosis Autophagy 

Notes

Acknowledgments

The Project was supported by the National Natural Science Foundation of China (30871024 and 81170154). The authors are indebted to Dr. Shi-Yuan Cheng for an extensive edit on the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10495_2014_1074_MOESM1_ESM.pdf (1.6 mb)
Supplementary material 1 (PDF 1611 kb)

References

  1. 1.
    Price MJ, Chou CC, Frantzen M, Miyamoto T, Kar S, Lee S, Shah PK, Martin BJ, Lill M, Forrester JS, Chen PS, Makkar RR (2006) Intravenous mesenchymal stem cell therapy early after reperfused acute myocardial infarction improves left ventricular function and alters electrophysiologic properties. Int J Cardiol 111(2):231–239. doi: 10.1016/j.ijcard.2005.07.036 CrossRefPubMedGoogle Scholar
  2. 2.
    Valina C, Pinkernell K, Song YH, Bai X, Sadat S, Campeau RJ, Le Jemtel TH, Alt E (2007) Intracoronary administration of autologous adipose tissue-derived stem cells improves left ventricular function, perfusion, and remodelling after acute myocardial infarction. Eur Heart J 28(21):2667–2677. doi: 10.1093/eurheartj/ehm426 CrossRefPubMedGoogle Scholar
  3. 3.
    Geng YJ (2003) Molecular mechanisms for cardiovascular stem cell apoptosis and growth in the hearts with atherosclerotic coronary disease and ischemic heart failure. Ann NY Acad Sci 1010:687–697CrossRefPubMedGoogle Scholar
  4. 4.
    Zhu W, Chen J, Cong X, Hu S, Chen X (2006) Hypoxia and serum deprivation-induced apoptosis in mesenchymal stem cells. Stem Cells 24(2):416–425. doi: 10.1634/stemcells.2005-0121 CrossRefPubMedGoogle Scholar
  5. 5.
    Lu L, Quinn MT, Sun Y (2004) Oxidative stress in the infarcted heart: role of de novo angiotensin II production. Biochem Biophys Res Commun 325(3):943–951. doi: 10.1016/j.bbrc.2004.10.106 CrossRefPubMedGoogle Scholar
  6. 6.
    Vanden Hoek T, Becker LB, Shao ZH, Li CQ, Schumacker PT (2000) Preconditioning in cardiomyocytes protects by attenuating oxidant stress at reperfusion. Circ Res 86(5):541–548CrossRefPubMedGoogle Scholar
  7. 7.
    Wei H, Li Z, Hu S, Chen X, Cong X (2010) Apoptosis of mesenchymal stem cells induced by hydrogen peroxide concerns both endoplasmic reticulum stress and mitochondrial death pathway through regulation of caspases, p38 and JNK. J Cell Biochem 111(4):967–978. doi: 10.1002/jcb.22785 CrossRefPubMedGoogle Scholar
  8. 8.
    Contos JJ, Chun J (2000) Genomic characterization of the lysophosphatidic acid receptor gene, lp(A2)/Edg4, and identification of a frameshift mutation in a previously characterized cDNA. Genomics 64(2):155–169. doi: 10.1006/geno.2000.6122 CrossRefPubMedGoogle Scholar
  9. 9.
    Contos JJ, Ishii I, Chun J (2000) Lysophosphatidic acid receptors. Mol Pharmacol 58(6):1188–1196PubMedGoogle Scholar
  10. 10.
    Kaestner L, Steffen P, Nguyen DB, Wang J, Wagner-Britz L, Jung A, Wagner C, Bernhardt I (2012) Lysophosphatidic acid induced red blood cell aggregation in vitro. Bioelectrochemistry 87:89–95. doi: 10.1016/j.bioelechem.2011.08.004 CrossRefPubMedGoogle Scholar
  11. 11.
    Tang N, Zhao Y, Feng R, Liu Y, Wang S, Wei W, Ding Q, An MS, Wen J, Li L (2013) Lysophosphatidic acid accelerates lung fibrosis by inducing differentiation of mesenchymal stem cells into myofibroblasts. J Cell Mol Med. doi: 10.1111/jcmm.12178 Google Scholar
  12. 12.
    Anliker B, Chun J (2004) Lysophospholipid G protein-coupled receptors. J Biol Chem 279(20):20555–20558. doi: 10.1074/jbc.R400013200 CrossRefPubMedGoogle Scholar
  13. 13.
    Chen X, Yang XY, Wang ND, Ding C, Yang YJ, You ZJ, Su Q, Chen JH (2003) Serum lysophosphatidic acid concentrations measured by dot immunogold filtration assay in patients with acute myocardial infarction. Scand J Clin Lab Invest 63(7–8):497–503CrossRefPubMedGoogle Scholar
  14. 14.
    Chen J, Baydoun AR, Xu R, Deng L, Liu X, Zhu W, Shi L, Cong X, Hu S, Chen X (2008) Lysophosphatidic acid protects mesenchymal stem cells against hypoxia and serum deprivation-induced apoptosis. Stem Cells 26(1):135–145. doi: 10.1634/stemcells.2007-0098 CrossRefPubMedGoogle Scholar
  15. 15.
    Li Z, Wei H, Liu X, Hu S, Cong X, Chen X (2010) LPA rescues ER stress-associated apoptosis in hypoxia and serum deprivation-stimulated mesenchymal stem cells. J Cell Biochem 111(4):811–820. doi: 10.1002/jcb.22731 CrossRefPubMedGoogle Scholar
  16. 16.
    Swarthout JT, Walling HW (2000) Lysophosphatidic acid: receptors, signaling and survival. Cell Mol Life Sci 57(13–14):1978–1985CrossRefPubMedGoogle Scholar
  17. 17.
    Ye X, Ishii I, Kingsbury MA, Chun J (2002) Lysophosphatidic acid as a novel cell survival/apoptotic factor. Biochim Biophys Acta 1585(2–3):108–113CrossRefPubMedGoogle Scholar
  18. 18.
    Guan JL, Simon AK, Prescott M, Menendez JA, Liu F, Wang F, Wang C, Wolvetang E, Vazquez-Martin A, Zhang J (2013) Autophagy in stem cells. Autophagy 9(6):830–849. doi: 10.4161/auto.24132 CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    Hamacher-Brady A, Brady NR, Gottlieb RA, Gustafsson AB (2006) Autophagy as a protective response to Bnip3-mediated apoptotic signaling in the heart. Autophagy 2(4):307–309CrossRefPubMedGoogle Scholar
  20. 20.
    Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211(2):134–143. doi: 10.1002/path.2094 CrossRefPubMedGoogle Scholar
  21. 21.
    Takagi H, Matsui Y, Sadoshima J (2007) The role of autophagy in mediating cell survival and death during ischemia and reperfusion in the heart. Antioxid Redox Signal 9(9):1373–1381. doi: 10.1089/ars.2007.1689 CrossRefPubMedGoogle Scholar
  22. 22.
    Baehrecke EH (2005) Autophagy: dual roles in life and death? Nat Rev Mol Cell Biol 6(6):505–510. doi: 10.1038/nrm1666 CrossRefPubMedGoogle Scholar
  23. 23.
    Codogno P, Meijer AJ (2005) Autophagy and signaling: their role in cell survival and cell death. Cell Death Differ 12(Suppl 2):1509–1518. doi: 10.1038/sj.cdd.4401751 CrossRefPubMedGoogle Scholar
  24. 24.
    Zhang Q, Yang YJ, Wang H, Dong QT, Wang TJ, Qian HY, Xu H (2012) Autophagy activation: a novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase/mammalian target of rapamycin pathway. Stem cell dev 21(8):1321–1332. doi: 10.1089/scd.2011.0684 CrossRefGoogle Scholar
  25. 25.
    Resnic FS, Wainstein M, Lee MK, Behrendt D, Wainstein RV, Ohno-Machado L, Kirshenbaum JM, Rogers CD, Popma JJ, Piana R (2003) No-reflow is an independent predictor of death and myocardial infarction after percutaneous coronary intervention. Am Heart J 145(1):42–46. doi: 10.1067/mhj.2003.36 CrossRefPubMedGoogle Scholar
  26. 26.
    Tanaka A, Kawarabayashi T, Nishibori Y, Sano T, Nishida Y, Fukuda D, Shimada K, Yoshikawa J (2002) No-reflow phenomenon and lesion morphology in patients with acute myocardial infarction. Circulation 105(18):2148–2152CrossRefPubMedGoogle Scholar
  27. 27.
    Hariharan N, Zhai P, Sadoshima J (2011) Oxidative stress stimulates autophagic flux during ischemia/reperfusion. Antioxid Redox Signal 14(11):2179–2190. doi: 10.1089/ars.2010.3488 CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Eisenberg-Lerner A, Bialik S, Simon HU, Kimchi A (2009) Life and death partners: apoptosis, autophagy and the cross-talk between them. Cell Death Differ 16(7):966–975. doi: 10.1038/cdd.2009.33 CrossRefPubMedGoogle Scholar
  29. 29.
    Urao N, McKinney RD, Fukai T, Ushio-Fukai M (2012) NADPH oxidase 2 regulates bone marrow microenvironment following hindlimb ischemia: role in reparative mobilization of progenitor cells. Stem Cell 30(5):923–934. doi: 10.1002/stem.1048 CrossRefGoogle Scholar
  30. 30.
    Nathan C, Ding A (2010) Snapshot: reactive oxygen intermediates (ROI). cell 140(6):951–951 e952. doi: 10.1016/j.cell.2010.03.008 CrossRefPubMedGoogle Scholar
  31. 31.
    Naka K, Muraguchi T, Hoshii T, Hirao A (2008) Regulation of reactive oxygen species and genomic stability in hematopoietic stem cells. Antioxid Redox Signal 10(11):1883–1894. doi: 10.1089/ars.2008.2114 CrossRefPubMedGoogle Scholar
  32. 32.
    Fang Y, Moore BJ, Bai Q, Cook KM, Herrick EJ, Nicholl MB (2013) Hydrogen peroxide enhances radiation-induced apoptosis and inhibition of melanoma cell proliferation. Anticancer Res 33(5):1799–1807PubMedGoogle Scholar
  33. 33.
    Pan H, Cheng L, Yang H, Zou W, Cheng R, Hu T (2014) Lysophosphatidic acid rescues human dental pulp cells from ischemia-induced apoptosis. J Endod 40(2):217–222. doi: 10.1016/j.joen.2013.07.015 CrossRefPubMedGoogle Scholar
  34. 34.
    Deng W, Wang DA, Gosmanova E, Johnson LR, Tigyi G (2003) LPA protects intestinal epithelial cells from apoptosis by inhibiting the mitochondrial pathway. Am J Physiol Gastrointest Liver Physiol 284(5):G821–G829. doi: 10.1152/ajpgi.00406.2002 PubMedGoogle Scholar
  35. 35.
    Sun Y, Kim NH, Ji L, Kim SH, Lee J, Rhee HJ (2013) Lysophosphatidic acid activates betacatenin/T cell factor signaling, which contributes to the suppression of apoptosis in H197 cells. Mol Med Rep 8(6):1729–1733. doi: 10.3892/mmr.2013.1743 PubMedGoogle Scholar
  36. 36.
    Binder BY, Genetos DC, Leach JK (2014) Lysophosphatidic acid protects human mesenchymal stromal cells from differentiation-dependent vulnerability to apoptosis. Tissue Eng Part A. doi: 10.1089/ten.TEA.2013.0487 PubMedGoogle Scholar
  37. 37.
    Chen J, Han Y, Zhu W, Ma R, Han B, Cong X, Hu S, Chen X (2006) Specific receptor subtype mediation of LPA-induced dual effects in cardiac fibroblasts. FEBS Lett 580(19):4737–4745. doi: 10.1016/j.febslet.2006.07.061 CrossRefPubMedGoogle Scholar
  38. 38.
    Kato K, Yoshikawa K, Tanabe E, Kitayoshi M, Fukui R, Fukushima N, Tsujiuchi T (2012) Opposite roles of LPA1 and LPA3 on cell motile and invasive activities of pancreatic cancer cells. Tumour Biol 33(5):1739–1744. doi: 10.1007/s13277-012-0433-0 CrossRefPubMedGoogle Scholar
  39. 39.
    Chen RJ, Chen SU, Chou CH, Lin MC (2012) Lysophosphatidic acid receptor 2/3-mediated IL-8-dependent angiogenesis in cervical cancer cells. Int J Cancer J Int Du Cancer 131(4):789–802. doi: 10.1002/ijc.26476 CrossRefGoogle Scholar
  40. 40.
    Taghavi P, Verhoeven E, Jacobs JJ, Lambooij JP, Stortelers C, Tanger E, Moolenaar WH, van Lohuizen M (2008) In vitro genetic screen identifies a cooperative role for LPA signaling and c-Myc in cell transformation. Oncogene 27(54):6806–6816. doi: 10.1038/onc.2008.294 CrossRefPubMedGoogle Scholar
  41. 41.
    Okabe K, Hayashi M, Kato K, Okumura M, Fukui R, Honoki K, Fukushima N, Tsujiuchi T (2013) Lysophosphatidic acid receptor-3 increases tumorigenicity and aggressiveness of rat hepatoma RH7777 cells. Mol Carcinog 52(4):247–254. doi: 10.1002/mc.21851 CrossRefPubMedGoogle Scholar
  42. 42.
    Sautin YY, Crawford JM, Svetlov SI (2001) Enhancement of survival by LPA via Erk1/Erk2 and PI 3-kinase/Akt pathways in a murine hepatocyte cell line. Am J Physiol Cell Physiol 281(6):C2010–C2019CrossRefPubMedGoogle Scholar
  43. 43.
    Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R, Yokoyama M, Mishima K, Saito I, Okano H, Mizushima N (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441(7095):885–889. doi: 10.1038/nature04724 CrossRefPubMedGoogle Scholar
  44. 44.
    Matsui Y, Takagi H, Qu X, Abdellatif M, Sakoda H, Asano T, Levine B, Sadoshima J (2007) Distinct roles of autophagy in the heart during ischemia and reperfusion: roles of AMP-activated protein kinase and Beclin 1 in mediating autophagy. Circ Res 100(6):914–922. doi: 10.1161/01.RES.0000261924.76669.36 CrossRefPubMedGoogle Scholar
  45. 45.
    Nishida K, Kyoi S, Yamaguchi O, Sadoshima J, Otsu K (2009) The role of autophagy in the heart. Cell Death Differ 16(1):31–38. doi: 10.1038/cdd.2008.163 CrossRefPubMedGoogle Scholar
  46. 46.
    Wang ZV, Rothermel BA, Hill JA (2010) Autophagy in hypertensive heart disease. J Biol Chem 285(12):8509–8514. doi: 10.1074/jbc.R109.025023 CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Yan L, Vatner DE, Kim SJ, Ge H, Masurekar M, Massover WH, Yang G, Matsui Y, Sadoshima J, Vatner SF (2005) Autophagy in chronically ischemic myocardium. Proc Natl Acad Sci USA 102(39):13807–13812. doi: 10.1073/pnas.0506843102 CrossRefPubMedCentralPubMedGoogle Scholar
  48. 48.
    Deng X, Zhang F, Rui W, Long F, Wang L, Feng Z, Chen D, Ding W (2013) PM2.5-induced oxidative stress triggers autophagy in human lung epithelial A549 cells. Toxicol In Vitro 27(6):1762–1770. doi: 10.1016/j.tiv.2013.05.004 CrossRefPubMedGoogle Scholar
  49. 49.
    Morales CR, Pedrozo Z, Lavandero S, Hill JA (2013) Oxidative stress and autophagy in cardiovascular homeostasis. Antioxid Redox Signal. doi: 10.1089/ars.2013.5359 PubMedGoogle Scholar
  50. 50.
    Luo Y, Zou P, Zou J, Wang J, Zhou D, Liu L (2011) Autophagy regulates ROS-induced cellular senescence via p21 in a p38 MAPKalpha dependent manner. Exp Gerontol 46(11):860–867. doi: 10.1016/j.exger.2011.07.005 CrossRefPubMedCentralPubMedGoogle Scholar
  51. 51.
    Chang CL, Ho MC, Lee PH, Hsu CY, Huang WP, Lee H (2009) S1P(5) is required for sphingosine 1-phosphate-induced autophagy in human prostate cancer PC-3 cells. Am J Physiol Cell Physiol 297(2):C451–C458. doi: 10.1152/ajpcell.00586.2008 CrossRefPubMedGoogle Scholar
  52. 52.
    Lavieu G, Scarlatti F, Sala G, Carpentier S, Levade T, Ghidoni R, Botti J, Codogno P (2006) Regulation of autophagy by sphingosine kinase 1 and its role in cell survival during nutrient starvation. J Biol Chem 281(13):8518–8527. doi: 10.1074/jbc.M506182200 CrossRefPubMedGoogle Scholar
  53. 53.
    Daido S, Kanzawa T, Yamamoto A, Takeuchi H, Kondo Y, Kondo S (2004) Pivotal role of the cell death factor BNIP3 in ceramide-induced autophagic cell death in malignant glioma cells. Cancer Res 64(12):4286–4293. doi: 10.1158/0008-5472.CAN-03-3084 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Xian-Yun Wang
    • 1
  • Xue-Song Fan
    • 1
  • Lin Cai
    • 1
  • Si Liu
    • 1
  • Xiang-Feng Cong
    • 1
  • Xi Chen
    • 1
    Email author
  1. 1.State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Centre for Cardiovascular DiseasesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina

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