Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
권호 표지
DOI QR코드

DOI QR Code

Epoxyeicosatrienoic Acid Inhibits the Apoptosis of Cerebral Microvascular Smooth Muscle Cells by Oxygen Glucose Deprivation via Targeting the JNK/c-Jun and mTOR Signaling Pathways

  • Qu, Youyang (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University) ;
  • Liu, Yu (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University) ;
  • Zhu, Yanmei (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University) ;
  • Chen, Li (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University) ;
  • Sun, Wei (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University) ;
  • Zhu, Yulan (Department of Neurology, the Second Affiliated Hospital of Harbin Medical University)
  • Received : 2017.05.19
  • Accepted : 2017.10.10
  • Published : 2017.11.30
Download PDF
⟨ Previous Next ⟩

Abstract

As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions. RAPA (serine/threonine kinase Mammalian Target of Rapamycin), a specific mTOR inhibitor, could elevate the level of oxygen free radicals in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. However, SP600125, a specific JNK (c-Jun N-terminal protein kinase) pathway inhibitor, could attenuate oxygen free radicals levels in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. These results strongly suggest that EETs exert protective functions during the growth and apoptosis of CSMCs, via the JNK/c-Jun and mTOR signaling pathways in vitro. We are the first to disclose the beneficial roles and underlying mechanism of 14,15-EET in CSMC under OGD conditions.

Keywords

References

  1. Abbott, N.J., Ronnback, L., and Hansson, E. (2006). Astrocyteendothelial interactions at the blood-brain barrier. Nat. Rev. Neurosci. 7, 41-53. https://doi.org/10.1038/nrn1824
  2. Benoit, M., Dormond-Meuwly, A., Demartines, N., and Dormond, O. (2011). Targeting the JNK signaling pathway potentiates the antiproliferative efficacy of rapamycin in LS174T colon cancer cells. J. Surg. Res. 167, e193-198. https://doi.org/10.1016/j.jss.2011.01.015
  3. Brakemeier, S., Kersten, A., Eichler, I., Grgic, I., Zakrzewicz, A., Hopp, H., Kohler, R., and Hoyer, J. (2003). Shear stress-induced up-regulation of the intermediate-conductance Ca(2+)-activated K(+) channel in human endothelium. Cardiov. Res. 60, 488-496. https://doi.org/10.1016/j.cardiores.2003.09.010
  4. Briones, A.M., and Touyz, R.M. (2010). Oxidative stress and hypertension: current concepts. Curr. Hypertension Rep. 12, 135-142. https://doi.org/10.1007/s11906-010-0100-z
  5. Brooks, C., and Dong, Z. (2007). Regulation of mitochondrial morphological dynamics during apoptosis by Bcl-2 family proteins: a key in Bak? Cell Cycle 6, 3043-3047. https://doi.org/10.4161/cc.6.24.5115
  6. Charriaut-Marlangue, C. (2004). Apoptosis: a target for neuroprotection. Therapie 59, 185-190. https://doi.org/10.2515/therapie:2004035
  7. Chen, L., Liu, L., Luo, Y., and Huang, S. (2008). MAPK and mTOR pathways are involved in cadmium-induced neuronal apoptosis. J. Neurochem. 105, 251-261. https://doi.org/10.1111/j.1471-4159.2007.05133.x
  8. Chung, J.J., Cho, S., Kwon, Y.K., Kim, D.H., and Kim, K. (2000). Activation of retinoic acid receptor gamma induces proliferation of immortalized hippocampal progenitor cells. Brain Res. Mol. Brain Res. 83, 52-62. https://doi.org/10.1016/S0169-328X(00)00196-0
  9. del Zoppo, G.J., and Mabuchi, T. (2003). Cerebral microvessel responses to focal ischemia. J. Cerebral Blood Flow Metabol. 23, 879-894. https://doi.org/10.1097/01.WCB.0000078322.96027.78
  10. Dirnagl, U. (2012). Pathobiology of injury after stroke: the neurovascular unit and beyond. Ann. N Y Acad Sci. 1268, 21-25. https://doi.org/10.1111/j.1749-6632.2012.06691.x
  11. Drobny, M., and Kurca, E. (2000). Possible extrapyramidal system degradation in Parkinson's disease. Brain Res. Bull. 53, 425-430. https://doi.org/10.1016/S0361-9230(00)00367-1
  12. Fang, X., Chen, P., and Moore, S.A. (2002). The oxygen radical scavenger pyrrolidine dithiocarbamate enhances interleukin-1betainduced cyclooxygenase-2 expression in cerebral microvascular smooth muscle cells. Microvasc. Res. 64, 405-413. https://doi.org/10.1006/mvre.2002.2431
  13. Fujishita, T., Aoki, M., and Taketo, M.M. (2011). JNK signaling promotes intestinal tumorigenesis through activation of mTOR complex 1 in Apc(Delta716) mice. Gastroenterology 140, 1556-1563 e1556. https://doi.org/10.1053/j.gastro.2011.02.007
  14. Gebremedhin, D., Ma, Y.H., Falck, J.R., Roman, R.J., VanRollins, M., and Harder, D.R. (1992). Mechanism of action of cerebral epoxyeicosatrienoic acids on cerebral arterial smooth muscle. Am. J. Physiol. 263, H519-525.
  15. Granger, D.N., and Kvietys, P.R. (2015). Reperfusion injury and reactive oxygen species: The evolution of a concept. Redox Biol. 6, 524-551. https://doi.org/10.1016/j.redox.2015.08.020
  16. Heil, M., and Schaper, W. (2004). Influence of mechanical, cellular, and molecular factors on collateral artery growth (arteriogenesis). Circ. Res. 95, 449-458. https://doi.org/10.1161/01.RES.0000141145.78900.44
  17. Huang, H., Zhong, R., Xia, Z., Song, J., and Feng, L. (2014). Neuroprotective effects of rhynchophylline against ischemic brain injury via regulation of the Akt/mTOR and TLRs signaling pathways. Molecules 19, 11196-11210. https://doi.org/10.3390/molecules190811196
  18. Iadecola, C. (2004). Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat. Rev. Neurosci. 5, 347-360. https://doi.org/10.1038/nrn1387
  19. Imig, J.D. (2010). Targeting epoxides for organ damage in hypertension. J. Cardiovasc. Pharmacol. 56, 329-335. https://doi.org/10.1097/FJC.0b013e3181e96e0c
  20. Iyer, A. and Brown, L. (2009). Is mycophenolate more than just an immunosuppressant?--An overview. Indian J. Biochem. Biophy. 46, 25-30.
  21. Koehler, R.C., Roman, R.J. and Harder, D.R. (2009). Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 32, 160-169. https://doi.org/10.1016/j.tins.2008.11.005
  22. Kumar, S., Kain, V. and Sitasawad, S.L. (2012). High glucose-induced $Ca^{2+}$ overload and oxidative stress contribute to apoptosis of cardiac cells through mitochondrial dependent and independent pathways. Biochim. Biophys. Acta 1820, 907-920. https://doi.org/10.1016/j.bbagen.2012.02.010
  23. Lakshmi, S.V., Padmaja, G., Kuppusamy, P., and Kutala, V.K. (2009). Oxidative stress in cardiovascular disease. Indian J. Biochem. Biophy. 46, 421-440.
  24. Lee, R.M. (1995). Morphology of cerebral arteries. Pharmacol. Therapeutics 66, 149-173. https://doi.org/10.1016/0163-7258(94)00071-A
  25. Ma, J., Zhang, L., Han, W., Shen, T., Ma, C., Liu, Y., Nie, X., Liu, M., Ran, Y., and Zhu, D. (2012). Activation of JNK/c-Jun is required for the proliferation, survival, and angiogenesis induced by EET in pulmonary artery endothelial cells. J. Lipid Res. 53, 1093-1105. https://doi.org/10.1194/jlr.M024398
  26. Mabuchi, T., Lucero, J., Feng, A., Koziol, J.A., and del Zoppo, G.J. (2005). Focal cerebral ischemia preferentially affects neurons distant from their neighboring microvessels. J. Cerebral Blood Flow Metabol. 25, 257-266. https://doi.org/10.1038/sj.jcbfm.9600027
  27. Medhora, M., Narayanan, J., and Harder, D. (2001). Dual regulation of the cerebral microvasculature by epoxyeicosatrienoic acids. Trends Cardiovasc. Med. 11, 38-42. https://doi.org/10.1016/S1050-1738(01)00082-2
  28. Meng, L., and Yu, B. (2011). Oxygen- and glucose-deprived culture promotes cell proliferation and invasion of vascular smooth muscle cells. Int. J. Mol. Med. 28, 777-783.
  29. Okuno, S., Saito, A., Hayashi, T., and Chan, P.H. (2004). The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. J. Neurosci. 24, 7879-7887. https://doi.org/10.1523/JNEUROSCI.1745-04.2004
  30. Palomares, S.M., and Cipolla, M.J. (2011). Vascular protection following cerebral ischemia and reperfusion. J. Neurol. Neurophysiol. 2011.
  31. Qu, Y.Y., Yuan, M.Y., Liu, Y., Xiao, X.J., and Zhu, Y.L. (2015). The protective effect of epoxyeicosatrienoic acids on cerebral ischemia/reperfusion injury is associated with PI3K/Akt pathway and ATP-sensitive potassium channels. Neurochem. Res. 40, 1-14. https://doi.org/10.1007/s11064-014-1456-2
  32. Robertson, G.S., Crocker, S.J., Nicholson, D.W., and Schulz, J.B. (2000). Neuroprotection by the inhibition of apoptosis. Brain pathol. 10, 283-292. https://doi.org/10.1111/j.1750-3639.2000.tb00262.x
  33. Sawada, M., Nakashima, S., Banno, Y., Yamakawa, H., Takenaka, K., Shinoda, J., Nishimura, Y., Sakai, N., and Nozawa, Y. (2000). Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells. Oncogene 19, 3508-3520. https://doi.org/10.1038/sj.onc.1203699
  34. Schmidt-Kastner, R., Truettner, J., Zhao, W., Belayev, L., Krieger, C., Busto, R., and Ginsberg, M.D. (2000). Differential changes of bax, caspase-3 and p21 mRNA expression after transient focal brain ischemia in the rat. Brain Res. Mol. Brain Res. 79, 88-101. https://doi.org/10.1016/S0169-328X(00)00104-2
  35. Scholz, D., Ito, W., Fleming, I., Deindl, E., Sauer, A., Wiesnet, M., Busse, R., Schaper, J., and Schaper, W. (2000). Ultrastructure and molecular histology of rabbit hind-limb collateral artery growth (arteriogenesis). Virchows Archiv. 436, 257-270. https://doi.org/10.1007/s004280050039
  36. Selimi, F., Campana, A., Weitzman, J., Vogel, M.W., and Mariani, J. (2000). Bax and p53 are differentially involved in the regulation of caspase-3 expression and activation during neurodegeneration in Lurcher mice. C R Acad. Sci. III. 323, 967-973. https://doi.org/10.1016/S0764-4469(00)01243-9
  37. Sudhahar, V., Shaw, S., and Imig, J.D. (2010). Epoxyeicosatrienoic acid analogs and vascular function. Curr. Medicinal Chem. 17, 1181-1190. https://doi.org/10.2174/092986710790827843
  38. Takuma, K., Baba, A., and Matsuda, T. (2004). Astrocyte apoptosis: implications for neuroprotection. Prog. Neurobiol. 72, 111-127. https://doi.org/10.1016/j.pneurobio.2004.02.001
  39. Tatton, N.A. (2000). Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson's disease. Exper. Neurol. 166, 29-43. https://doi.org/10.1006/exnr.2000.7489
  40. Tong, H., Chen, W., Steenbergen, C., and Murphy, E. (2000). Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ. Res. 87, 309-315. https://doi.org/10.1161/01.RES.87.4.309
  41. von Leden, R.E., Yauger, Y.J., Khayrullina, G., and Byrnes, K. (2016). Review: CNS ijury and NADPH oxidase: oxidative stress and therapeutic targets. J. Neurotrauma. 34, 755-764.
  42. Wang, H., Lin, L., Jiang, J., Wang, Y., Lu, Z.Y., Bradbury, J.A., Lih, F.B., Wang, D.W., and Zeldin, D.C. (2003). Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways. J. Pharmacol. Exper. Ther. 307, 753-764. https://doi.org/10.1124/jpet.103.052787
  43. Zhang, J., Xia, Y., Xu, Z., and Deng, X. (2016). Propofol suppressed hypoxia/reoxygenation-induced apoptosis in HBVSMC by regulation of the expression of Bcl-2, Bax, Caspase3, Kir6.1, and p-JNK. Oxid. Med. Cell. Longev. 2016, 1518738.

Cited by

  1. Soluble Epoxide Hydrolase Inhibition Attenuates Excitotoxicity Involving 14,15-Epoxyeicosatrienoic Acid-Mediated Astrocytic Survival and Plasticity to Preserve Glutamate Homeostasis vol.56, pp.12, 2017, https://doi.org/10.1007/s12035-019-01669-8
  2. Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke vol.21, pp.10, 2017, https://doi.org/10.3390/ijms21103618
  3. Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration vol.12, pp.11, 2020, https://doi.org/10.3390/nu12113523