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Basic Research in Cardiology

, 112:60 | Cite as

MicroRNA-143 promotes cardiac ischemia-mediated mitochondrial impairment by the inhibition of protein kinase Cepsilon

  • Hong Hong
  • Ting Tao
  • Si Chen
  • Chaoqi Liang
  • Yue Qiu
  • Yuhong Zhou
  • Rong ZhangEmail author
Original Contribution

Abstract

The cardioprotection of protein kinase Cepsilon (PKCε) against myocardial infarction (MI) mediated by its anti-apoptotic property and underlying mechanism of targeted regulation by microRNA (miRNA) are not established. MI-induced injury, PKCε expression, and targeted regulation of miRNA-143 (miR-143) to PKCε have been evaluated using animal MI and cellular hypoxic models conjugated with series of state-of-art molecular techniques. The results demonstrated that PKCε significantly downregulated along with increased infarcted area and apoptotic and necrotic damage in MI model, and the targeted relationship and potential binding profile were established between miR-143 and PKCε. Both in vivo and in vitro ischemic tests showed that miR-143 induced apoptosis and necrosis, which was reversed by antagomiR-143 or AMO-143. The upregulation of miR-143 by transfection of miR-143 in vitro also induced cell loss, and this effect of miR-143 was completely reversed by co-transfection of miR-143 with AMO-143. The identically deleterious action of miR-143 on mitochondrial membrane potential and ATP synthesis was also observed in both animal MI and cellular hypoxic models, as well as miR-143 overexpressed models and converted by either antagomiR or AMO. Importantly, overexpression of miR-143 downregulated PKCε in all tested models and this downregulation was reversed in the presence of antagomiR or AMO. The direct targeted regulation of miR-143 on PKCε was confirmed by luciferase reporter and miRNA-masking tests. In conclusion, MI-mediated upregulation of miR-143 inhibits PKCε expression and consequently interference with the cardioprotection of PKCε to mitochondrial, and leads to mitochondrial membrane potential dissipation and myocardial death eventually.

Keywords

MicroRNA-143 Myocardial infarction PKCε Mitochondria Apoptosis Necrosis 

Abbreviations

PKCε

Protein kinase Cepsilon

I/R

Ischemia/reperfusion

IPC

Preconditioning

MI

Myocardial infarction

TEM

Transmission electron microscopy

NRVCs

Neonatal rat ventricular cardiomyocytes

mitoKATP

Mitochondrial ATP-sensitive K(+) channel

mPTP

Mitochondrial permeability transition pore

ΔΨm

Mitochondrial membrane potential

Notes

Acknowledgements

Financial support was provided by the National Natural Science Foundation of China (81102434, 81470523, and 81673425).

Compliance with ethical standards

Conflict of interest

All the authors declare no competing financial interests.

References

  1. 1.
    Ai J, Zhang R, Gao X, Niu HF, Wang N, Xu Y, Li Y, Ma N, Sun LH, Pan ZW, Li WM, Yang BF (2012) Overexpression of microRNA-1 impairs cardiac contractile function by damaging sarcomere assembly. Cardiovasc Res 95:385–393. doi: 10.1093/cvr/cvs196 CrossRefPubMedGoogle Scholar
  2. 2.
    Aurora AB, Mahmoud AI, Luo X, Johnson BA, van Rooij E, Matsuzaki S, Humphries KM, Hill JA, Bassel-Duby R, Sadek HA, Olson EN (2012) MicroRNA-214 protects the mouse heart from ischemic injury by controlling Ca(2)(+) overload and cell death. J Clin Investig 122:1222–1232. doi: 10.1172/JCI59327 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Avgeris M, Mavridis K, Tokas T, Stravodimos K, Fragoulis EG, Scorilas A (2015) Uncovering the clinical utility of miR-143, miR-145 and miR-224 for predicting the survival of bladder cancer patients following treatment. Carcinogenesis 36:528–537. doi: 10.1093/carcin/bgv024 CrossRefPubMedGoogle Scholar
  4. 4.
    Baines CP, Song CX, Zheng YT, Wang GW, Zhang J, Wang OL, Guo Y, Bolli R, Cardwell EM, Ping P (2003) Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circ Res 92:873–880. doi: 10.1161/01.RES.0000069215.36389.8D CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P (2017) Heart disease and stroke statistics—2017 update: a report from the American Heart Association. Circulation 135:e146–e603. doi: 10.1161/CIR.0000000000000485 CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Budas GR, Mochly-Rosen D (2007) Mitochondrial protein kinase Cepsilon (PKCepsilon): emerging role in cardiac protection from ischaemic damage. Biochem Soc Trans 35:1052–1054. doi: 10.1042/BST0351052 CrossRefPubMedGoogle Scholar
  7. 7.
    Cabrera-Fuentes HA, Alba-Alba C, Aragones J, Bernhagen J, Boisvert WA, Botker HE, Cesarman-Maus G, Fleming I, Garcia-Dorado D, Lecour S, Liehn E, Marber MS, Marina N, Mayr M, Perez-Mendez O, Miura T, Ruiz-Meana M, Salinas-Estefanon EM, Ong SB, Schnittler HJ, Sanchez-Vega JT, Sumoza-Toledo A, Vogel CW, Yarullina D, Yellon DM, Preissner KT, Hausenloy DJ (2016) Meeting report from the 2nd International Symposium on New Frontiers in Cardiovascular Research. Protecting the cardiovascular system from ischemia: between bench and bedside. Basic Res Cardiol 111:7. doi: 10.1007/s00395-015-0527-0 CrossRefPubMedGoogle Scholar
  8. 8.
    Cabrera-Fuentes HA, Aragones J, Bernhagen J, Boening A, Boisvert WA, Botker HE, Bulluck H, Cook S, Di Lisa F, Engel FB, Engelmann B, Ferrazzi F, Ferdinandy P, Fong A, Fleming I, Gnaiger E, Hernandez-Resendiz S, Kalkhoran SB, Kim MH, Lecour S, Liehn EA, Marber MS, Mayr M, Miura T, Ong SB, Peter K, Sedding D, Singh MK, Suleiman MS, Schnittler HJ, Schulz R, Shim W, Tello D, Vogel CW, Walker M, Li QO, Yellon DM, Hausenloy DJ, Preissner KT (2016) From basic mechanisms to clinical applications in heart protection, new players in cardiovascular diseases and cardiac theranostics: meeting report from the third international symposium on “New frontiers in cardiovascular research”. Basic Res Cardiol 111:69. doi: 10.1007/s00395-016-0586-x CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Cho YS (2014) Perspectives on the therapeutic modulation of an alternative cell death, programmed necrosis (review). Int J Mol Med 33:1401–1406. doi: 10.3892/ijmm.2014.1716 CrossRefPubMedGoogle Scholar
  10. 10.
    Climent M, Quintavalle M, Miragoli M, Chen J, Condorelli G, Elia L (2015) TGFbeta triggers miR-143/145 transfer from smooth muscle cells to endothelial cells, thereby modulating vessel stabilization. Circ Res 116:1753–1764. doi: 10.1161/CIRCRESAHA.116.305178 CrossRefPubMedGoogle Scholar
  11. 11.
    Cordes KR, Sheehy NT, White MP, Berry EC, Morton SU, Muth AN, Lee TH, Miano JM, Ivey KN, Srivastava D (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460:705–710. doi: 10.1038/nature08195 PubMedPubMedCentralGoogle Scholar
  12. 12.
    Costa AD, Garlid KD (2008) Intramitochondrial signaling: interactions among mitoKATP, PKCepsilon, ROS, and MPT. Am J Physiol Heart Circ Physiol 295:H874–H882. doi: 10.1152/ajpheart.01189.2007 CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Costa AD, Jakob R, Costa CL, Andrukhiv K, West IC, Garlid KD (2006) The mechanism by which the mitochondrial ATP-sensitive K+ channel opening and H2O2 inhibit the mitochondrial permeability transition. J Biol Chem 281:20801–20808. doi: 10.1074/jbc.M600959200 CrossRefPubMedGoogle Scholar
  14. 14.
    de Gonzalo-Calvo D, Cenarro A, Civeira F, Llorente-Cortes V (2016) microRNA expression profile in human coronary smooth muscle cell-derived microparticles is a source of biomarkers. Clin Investig Arterioscler 28:167–177. doi: 10.1016/j.arteri.2016.05.005 CrossRefPubMedGoogle Scholar
  15. 15.
    Deacon DC, Nevis KR, Cashman TJ, Zhou Y, Zhao L, Washko D, Guner-Ataman B, Burns CG, Burns CE (2010) The miR-143-adducin3 pathway is essential for cardiac chamber morphogenesis. Development 137:1887–1896. doi: 10.1242/dev.050526 CrossRefPubMedGoogle Scholar
  16. 16.
    Deng L, Blanco FJ, Stevens H, Lu R, Caudrillier A, McBride M, McClure JD, Grant J, Thomas M, Frid M, Stenmark K, White K, Seto AG, Morrell NW, Bradshaw AC, MacLean MR, Baker AH (2015) MicroRNA-143 activation regulates smooth muscle and endothelial cell crosstalk in pulmonary arterial hypertension. Circ Res 117:870–883. doi: 10.1161/CIRCRESAHA.115.306806 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Duquesnes N, Lezoualc’h F, Crozatier B (2011) PKC-delta and PKC-epsilon: foes of the same family or strangers? J Mol Cell Cardiol 51:665–673. doi: 10.1016/j.yjmcc.2011.07.013 CrossRefPubMedGoogle Scholar
  18. 18.
    Eisenhardt SU, Weiss JB, Smolka C, Maxeiner J, Pankratz F, Bemtgen X, Kustermann M, Thiele JR, Schmidt Y, Bjoern Stark G, Moser M, Bode C, Grundmann S (2015) MicroRNA-155 aggravates ischemia–reperfusion injury by modulation of inflammatory cell recruitment and the respiratory oxidative burst. Basic Res Cardiol 110:32. doi: 10.1007/s00395-015-0490-9 CrossRefPubMedGoogle Scholar
  19. 19.
    Gustafsson AB, Gottlieb RA (2008) Heart mitochondria: gates of life and death. Cardiovasc Res 77:334–343. doi: 10.1093/cvr/cvm005 CrossRefPubMedGoogle Scholar
  20. 20.
    Hang P, Sun C, Guo J, Zhao J, Du Z (2016) BDNF-mediates down-regulation of microRNA-195 inhibits ischemic cardiac apoptosis in rats. Int J Biol Sci 12:979–989. doi: 10.7150/ijbs.15071 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Hausenloy DJ, Botker HE, Engstrom T, Erlinge D, Heusch G, Ibanez B, Kloner RA, Ovize M, Yellon DM, Garcia-Dorado D (2017) Targeting reperfusion injury in patients with ST-segment elevation myocardial infarction: trials and tribulations. Eur Heart J 38:935–941. doi: 10.1093/eurheartj/ehw145 PubMedGoogle Scholar
  22. 22.
    He Z, Yi J, Liu X, Chen J, Han S, Jin L, Chen L, Song H (2016) MiR-143-3p functions as a tumor suppressor by regulating cell proliferation, invasion and epithelial-mesenchymal transition by targeting QKI-5 in esophageal squamous cell carcinoma. Mol Cancer 15:51. doi: 10.1186/s12943-016-0533-3 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Hergenreider E, Heydt S, Treguer K, Boettger T, Horrevoets AJ, Zeiher AM, Scheffer MP, Frangakis AS, Yin X, Mayr M, Braun T, Urbich C, Boon RA, Dimmeler S (2012) Atheroprotective communication between endothelial cells and smooth muscle cells through miRNAs. Nat Cell Biol 14:249–256. doi: 10.1038/ncb2441 CrossRefPubMedGoogle Scholar
  24. 24.
    Heusch G (2015) Molecular basis of cardioprotection: signal transduction in ischemic pre-, post-, and remote conditioning. Circ Res 116:674–699. doi: 10.1161/CIRCRESAHA.116.305348 CrossRefPubMedGoogle Scholar
  25. 25.
    Heusch G, Gersh BJ (2017) The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J 38:774–784. doi: 10.1093/eurheartj/ehw224 PubMedGoogle Scholar
  26. 26.
    Hinkel R, Penzkofer D, Zuhlke S, Fischer A, Husada W, Xu QF, Baloch E, van Rooij E, Zeiher AM, Kupatt C, Dimmeler S (2013) Inhibition of microRNA-92a protects against ischemia/reperfusion injury in a large-animal model. Circulation 128:1066–1075. doi: 10.1161/CIRCULATIONAHA.113.001904 CrossRefPubMedGoogle Scholar
  27. 27.
    Huang FT, Peng JF, Cheng WJ, Zhuang YY, Wang LY, Li CQ, Tang J, Chen WY, Li YH, Zhang SN (2017) MiR-143 targeting TAK1 attenuates pancreatic ductal adenocarcinoma progression via MAPK and NF-kappaB pathway in vitro. Dig Dis Sci 62:944–957. doi: 10.1007/s10620-017-4472-7 CrossRefPubMedGoogle Scholar
  28. 28.
    Hund TJ, Lerner DL, Yamada KA, Schuessler RB, Saffitz JE (2007) Protein kinase Cepsilon mediates salutary effects on electrical coupling induced by ischemic preconditioning. Heart Rhythm 4:1183–1193. doi: 10.1016/j.hrthm.2007.05.030 CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Kabir AM, Clark JE, Tanno M, Cao X, Hothersall JS, Dashnyam S, Gorog DA, Bellahcene M, Shattock MJ, Marber MS (2006) Cardioprotection initiated by reactive oxygen species is dependent on activation of PKCepsilon. Am J Physiol Heart Circ Physiol 291:H1893–H1899. doi: 10.1152/ajpheart.00798.2005 CrossRefPubMedGoogle Scholar
  30. 30.
    Ke ZP, Xu P, Shi Y, Gao AM (2016) MicroRNA-93 inhibits ischemia–reperfusion induced cardiomyocyte apoptosis by targeting PTEN. Oncotarget 7:28796–28805. doi: 10.18632/oncotarget.8941 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Kent OA, McCall MN, Cornish TC, Halushka MK (2014) Lessons from miR-143/145: the importance of cell-type localization of miRNAs. Nucleic Acids Res 42:7528–7538. doi: 10.1093/nar/gku461 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kroemer G, Galluzzi L, Brenner C (2007) Mitochondrial membrane permeabilization in cell death. Physiol Rev 87:99–163. doi: 10.1152/physrev.00013.2006 CrossRefPubMedGoogle Scholar
  33. 33.
    Kung G, Konstantinidis K, Kitsis RN (2011) Programmed necrosis, not apoptosis, in the heart. Circ Res 108:1017–1036. doi: 10.1161/CIRCRESAHA.110.225730 CrossRefPubMedGoogle Scholar
  34. 34.
    Li D, Wang J, Hou J, Fu J, Liu J, Lin R (2016) Salvianolic acid B induced upregulation of miR-30a protects cardiac myocytes from ischemia/reperfusion injury. BMC Complement Altern Med 16:336. doi: 10.1186/s12906-016-1275-x CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Li WH, Wu HJ, Li YX, Pan HG, Meng T, Wang X (2016) MicroRNA-143 promotes apoptosis of osteosarcoma cells by caspase-3 activation via targeting Bcl-2. Biomed Pharmacother 80:8–15. doi: 10.1016/j.biopha.2016.03.001 CrossRefPubMedGoogle Scholar
  36. 36.
    Li X, Zeng Z, Li Q, Xu Q, Xie J, Hao H, Luo G, Liao W, Bin J, Huang X, Liao Y (2015) Inhibition of microRNA-497 ameliorates anoxia/reoxygenation injury in cardiomyocytes by suppressing cell apoptosis and enhancing autophagy. Oncotarget 6:18829–18844. doi: 10.18632/oncotarget.4774 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Linkermann A, Brasen JH, Darding M, Jin MK, Sanz AB, Heller JO, De Zen F, Weinlich R, Ortiz A, Walczak H, Weinberg JM, Green DR, Kunzendorf U, Krautwald S (2013) Two independent pathways of regulated necrosis mediate ischemia–reperfusion injury. Proc Natl Acad Sci USA 110:12024–12029. doi: 10.1073/pnas.1305538110 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Liu L, Zhang G, Liang Z, Liu X, Li T, Fan J, Bai J, Wang Y (2014) MicroRNA-15b enhances hypoxia/reoxygenation-induced apoptosis of cardiomyocytes via a mitochondrial apoptotic pathway. Apoptosis 19:19–29. doi: 10.1007/s10495-013-0899-2 CrossRefPubMedGoogle Scholar
  39. 39.
    Liu Q, Du GQ, Zhu ZT, Zhang C, Sun XW, Liu JJ, Li X, Wang YS, Du WJ (2015) Identification of apoptosis-related microRNAs and their target genes in myocardial infarction post-transplantation with skeletal myoblasts. J Transl Med 13:270. doi: 10.1186/s12967-015-0603-0 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Luedde M, Lutz M, Carter N, Sosna J, Jacoby C, Vucur M, Gautheron J, Roderburg C, Borg N, Reisinger F, Hippe HJ, Linkermann A, Wolf MJ, Rose-John S, Lullmann-Rauch R, Adam D, Flogel U, Heikenwalder M, Luedde T, Frey N (2014) RIP3, a kinase promoting necroptotic cell death, mediates adverse remodelling after myocardial infarction. Cardiovasc Res 103:206–216. doi: 10.1093/cvr/cvu146 CrossRefPubMedGoogle Scholar
  41. 41.
    Miao Y, Zhang LF, Guo R, Liang S, Zhang M, Shi S, Shang-Guan CF, Liu MF, Li B (2016) (18)F-FDG PET/CT for monitoring the response of breast cancer to miR-143-based therapeutics by targeting tumor glycolysis. Mol Ther Nucleic Acids 5:e357. doi: 10.1038/mtna.2016.72 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Miyasaka KY, Kida YS, Banjo T, Ueki Y, Nagayama K, Matsumoto T, Sato M, Ogura T (2011) Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143. Mech Dev 128:18–28. doi: 10.1016/j.mod.2010.09.002 CrossRefPubMedGoogle Scholar
  43. 43.
    Oerlemans MI, Liu J, Arslan F, den Ouden K, van Middelaar BJ, Doevendans PA, Sluijter JP (2012) Inhibition of RIP1-dependent necrosis prevents adverse cardiac remodeling after myocardial ischemia–reperfusion in vivo. Basic Res Cardiol 107:270. doi: 10.1007/s00395-012-0270-8 CrossRefPubMedGoogle Scholar
  44. 44.
    Pan Z, Sun X, Ren J, Li X, Gao X, Lu C, Zhang Y, Sun H, Wang Y, Wang H, Wang J, Xie L, Lu Y, Yang B (2012) miR-1 exacerbates cardiac ischemia–reperfusion injury in mouse models. PLoS One 7:e50515. doi: 10.1371/journal.pone.0050515 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Piubelli C, Meraviglia V, Pompilio G, D’Alessandra Y, Colombo GI, Rossini A (2014) microRNAs and cardiac cell fate. Cells 3:802–823. doi: 10.3390/cells3030802 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Plasterk RH (2006) Micro RNAs in animal development. Cell 124:877–881. doi: 10.1016/j.cell.2006.02.030 CrossRefPubMedGoogle Scholar
  47. 47.
    Qin D, Wang X, Li Y, Yang L, Wang R, Peng J, Essandoh K, Mu X, Peng T, Han Q, Yu KJ, Fan GC (2016) MicroRNA-223-5p and -3p cooperatively suppress necroptosis in ischemic/reperfused hearts. J Biol Chem 291:20247–20259. doi: 10.1074/jbc.M116.732735 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Scruggs SB, Wang D, Ping P (2016) PRKCE gene encoding protein kinase C-epsilon-Dual roles at sarcomeres and mitochondria in cardiomyocytes. Gene 590:90–96. doi: 10.1016/j.gene.2016.06.016 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Shen JZ, Zhang YY, Fu HY, Wu DS, Zhou HR (2014) Overexpression of microRNA-143 inhibits growth and induces apoptosis in human leukemia cells. Oncol Rep 31:2035–2042. doi: 10.3892/or.2014.3078 CrossRefPubMedGoogle Scholar
  50. 50.
    Shen Y, Shen Z, Miao L, Xin X, Lin S, Zhu Y, Guo W, Zhu YZ (2015) miRNA-30 family inhibition protects against cardiac ischemic injury by regulating cystathionine-gamma-lyase expression. Antioxid Redox Signal 22:224–240. doi: 10.1089/ars.2014.5909 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Sivaraman V, Hausenloy DJ, Kolvekar S, Hayward M, Yap J, Lawrence D, Di Salvo C, Yellon DM (2009) The divergent roles of protein kinase C epsilon and delta in simulated ischaemia–reperfusion injury in human myocardium. J Mol Cell Cardiol 46:758–764. doi: 10.1016/j.yjmcc.2009.02.013 CrossRefPubMedGoogle Scholar
  52. 52.
    Sun X, Zhang L (2017) MicroRNA-143 suppresses oral squamous cell carcinoma (OSCC) cell growth, invasion and glucose metabolism through targeting Hexokinase2. Biosci Rep. doi: 10.1042/BSR20160404 Google Scholar
  53. 53.
    Tang Y, Wang Y, Park KM, Hu Q, Teoh JP, Broskova Z, Ranganathan P, Jayakumar C, Li J, Su H, Ramesh G, Kim IM (2015) MicroRNA-150 protects the mouse heart from ischaemic injury by regulating cell death. Cardiovasc Res 106:387–397. doi: 10.1093/cvr/cvv121 CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Tian S, Zhao W, Yang D, Yu Y, Zou J, Liu Z, Du Z (2016) Atorvastatin inhibits miR-143 expression: a protective mechanism against oxidative stress in cardiomyocytes. Int J Cardiol 211:115–118. doi: 10.1016/j.ijcard.2016.02.141 CrossRefPubMedGoogle Scholar
  55. 55.
    Tsai KL, Liang HJ, Yang ZD, Lue SI, Yang SL, Hsu C (2014) Early inactivation of PKCepsilon associates with late mitochondrial translocation of Bad and apoptosis in ventricle of septic rat. J Surg Res 186:278–286. doi: 10.1016/j.jss.2013.08.010 CrossRefPubMedGoogle Scholar
  56. 56.
    Vahlhaus C, Schulz R, Post H, Onallah R, Heusch G (1996) No prevention of ischemic preconditioning by the protein kinase C inhibitor staurosporine in swine. Circ Res 79:407–414CrossRefPubMedGoogle Scholar
  57. 57.
    Wang JX, Zhang XJ, Li Q, Wang K, Wang Y, Jiao JQ, Feng C, Teng S, Zhou LY, Gong Y, Zhou ZX, Liu J, Wang JL, Li PF (2015) MicroRNA-103/107 regulate programmed necrosis and myocardial ischemia/reperfusion injury through targeting FADD. Circ Res 117:352–363. doi: 10.1161/CIRCRESAHA.117.305781 CrossRefPubMedGoogle Scholar
  58. 58.
    Wang K, An T, Zhou LY, Liu CY, Zhang XJ, Feng C, Li PF (2015) E2F1-regulated miR-30b suppresses Cyclophilin D and protects heart from ischemia/reperfusion injury and necrotic cell death. Cell Death Differ 22:743–754. doi: 10.1038/cdd.2014.165 CrossRefPubMedGoogle Scholar
  59. 59.
    Wang K, Liu CY, Zhang XJ, Feng C, Zhou LY, Zhao Y, Li PF (2015) miR-361-regulated prohibitin inhibits mitochondrial fission and apoptosis and protects heart from ischemia injury. Cell Death Differ 22:1058–1068. doi: 10.1038/cdd.2014.200 CrossRefPubMedGoogle Scholar
  60. 60.
    Wang L, He J, Xu H, Xu L, Li N (2016) MiR-143 targets CTGF and exerts tumor-suppressing functions in epithelial ovarian cancer. Am J Transl Res 8:2716–2726PubMedPubMedCentralGoogle Scholar
  61. 61.
    Wang S, Zhang F, Zhao G, Cheng Y, Wu T, Wu B, Zhang YE (2017) Mitochondrial PKC-epsilon deficiency promotes I/R-mediated myocardial injury via GSK3beta-dependent mitochondrial permeability transition pore opening. J Cell Mol Med 21:2009–2021. doi: 10.1111/jcmm.13121 CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Wang X, Ha T, Zou J, Ren D, Liu L, Zhang X, Kalbfleisch J, Gao X, Williams D, Li C (2014) MicroRNA-125b protects against myocardial ischaemia/reperfusion injury via targeting p53-mediated apoptotic signalling and TRAF6. Cardiovasc Res 102:385–395. doi: 10.1093/cvr/cvu044 CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Wang Y, Men M, Yang W, Zheng H, Xue S (2015) MiR-31 downregulation protects against cardiac ischemia/reperfusion injury by targeting protein kinase C epsilon (PKCepsilon) directly. Cell Physiol Biochem 36:179–190. doi: 10.1159/000374062 CrossRefPubMedGoogle Scholar
  64. 64.
    Xu H, Jin L, Chen Y, Li J (2016) Downregulation of microRNA-429 protects cardiomyocytes against hypoxia-induced apoptosis by increasing Notch1 expression. Int J Mol Med 37:1677–1685. doi: 10.3892/ijmm.2016.2558 CrossRefPubMedGoogle Scholar
  65. 65.
    Xu RH, Liu B, Wu JD, Yan YY, Wang JN (2016) miR-143 is involved in endothelial cell dysfunction through suppression of glycolysis and correlated with atherosclerotic plaques formation. Eur Rev Med Pharmacol Sci 20:4063–4071PubMedGoogle Scholar
  66. 66.
    Ytrehus K, Liu Y, Downey JM (1994) Preconditioning protects ischemic rabbit heart by protein kinase C activation. Am J Physiol 266:H1145–H1152PubMedGoogle Scholar
  67. 67.
    Yu H, Yang Z, Pan S, Yang Y, Tian J, Wang L, Sun W (2015) Hypoxic preconditioning promotes the translocation of protein kinase C epsilon binding with caveolin-3 at cell membrane not mitochondrial in rat heart. Cell Cycle 14:3557–3565. doi: 10.1080/15384101.2015.1084446 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Yuan F, Sun R, Li L, Jin B, Wang Y, Liang Y, Che G, Gao L, Zhang L (2016) A functional variant rs353292 in the flanking region of miR-143/145 contributes to the risk of colorectal cancer. Sci Rep 6:30195. doi: 10.1038/srep30195 CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Zhang N, Su Y, Xu L (2013) Targeting PKCepsilon by miR-143 regulates cell apoptosis in lung cancer. FEBS Lett 587:3661–3667. doi: 10.1016/j.febslet.2013.09.018 CrossRefPubMedGoogle Scholar
  70. 70.
    Zhao W, Wang P, Ma J, Liu YH, Li Z, Li ZQ, Wang ZH, Chen LY, Xue YX (2015) MiR-34a regulates blood-tumor barrier function by targeting protein kinase Cepsilon. Mol Biol Cell 26:1786–1796. doi: 10.1091/mbc.E14-10-1474 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Zhao W, Zhao SP, Zhao YH (2015) MicroRNA-143/-145 in cardiovascular diseases. Biomed Res Int 2015:531740. doi: 10.1155/2015/531740 PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  1. 1.Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education), College of PharmacyHarbin Medical UniversityHarbinChina

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