Table of Contents Author Guidelines Submit a Manuscript
Oxidative Medicine and Cellular Longevity
Volume 2017, Article ID 5736506, 13 pages
https://doi.org/10.1155/2017/5736506
Research Article

Homocysteine Induces Apoptosis of Human Umbilical Vein Endothelial Cells via Mitochondrial Dysfunction and Endoplasmic Reticulum Stress

1Department of Cardiology, Tangdu Hospital of the Fourth Military Medical University, Xi’an, China
2Department of Cardiology, Xian Yang Central Hospital, Xi’an, China
3Department of Cardiology, Shaanxi Provincial Chinese Traditional Medicine Hospital, Xi’an, China
4Department of Pharmacy, Tangdu Hospital of the Fourth Military Medical University, Xi’an, China

Correspondence should be addressed to Lianyou Zhao; moc.361@dtuoynailoahz

Received 12 December 2016; Revised 16 February 2017; Accepted 16 March 2017; Published 28 May 2017

Academic Editor: Igor A. Sobenin

Copyright © 2017 Zhimin Zhang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. M. R. Malinow, A. G. Bostom, and R. M. Krauss, “Homocyst(e)ine, diet, and cardiovascular diseases: a statement for healthcare professionals from the Nutrition Committee, American Heart Association,” Circulation, vol. 99, no. 1, pp. 178–182, 1999. View at Publisher · View at Google Scholar
  2. B. Marasini, M. Massarotti, and M. L. Biondi, “Homocysteine and vascular diseases,” Circulation, vol. 106, no. 7, article e33, 2002. View at Publisher · View at Google Scholar
  3. J. Thambyrajah and J. N. Townend, “Homocysteine and atherothrombosis - mechanisms for injury,” European Heart Journal, vol. 21, no. 12, pp. 967–974, 2000. View at Publisher · View at Google Scholar · View at Scopus
  4. Y. W. Kim, X. Z. West, and T. V. Byzova, “Inflammation and oxidative stress in angiogenesis and vascular disease,” Journal of Molecular Medicine, vol. 91, no. 3, pp. 323–328, 2013. View at Publisher · View at Google Scholar · View at Scopus
  5. Y. W. Kim and T. V. Byzova, “Oxidative stress in angiogenesis and vascular disease,” Blood, vol. 123, no. 5, pp. 625–631, 2014. View at Publisher · View at Google Scholar · View at Scopus
  6. Y. W. Xie and M. S. Wolin, “Role of nitric oxide and its interaction with superoxide in the suppression of cardiac muscle mitochondrial respiration,” Involvement in Response to Hypoxia/Reoxygenation. Circulation, vol. 94, no. 10, pp. 2580–2586, 1996. View at Publisher · View at Google Scholar
  7. D. E. Handy, Y. Zhang, and J. Loscalzo, “Homocysteine downregulates cellular glutathione peroxidase (GPx1) by decreasing translation,” The Journal of Biological Chemistry, vol. 280, no. 16, pp. 15518–15525, 2005. View at Publisher · View at Google Scholar · View at Scopus
  8. X. Wang, L. Cui, J. Joseph et al., “Homocysteine induces cardiomyocyte dysfunction and apoptosis through p38 MAPK-mediated increase in oxidant stress,” Journal of Molecular and Cellular Cardiology, vol. 52, no. 3, pp. 753–760, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. K. Okada, T. Minamino, Y. Tsukamoto et al., “Prolonged endoplasmic reticulum stress in hypertrophic and failing heart after aortic constriction: possible contribution of endoplasmic reticulum stress to cardiac myocyte apoptosis,” Circulation, vol. 110, no. 6, pp. 705–712, 2004. View at Publisher · View at Google Scholar · View at Scopus
  10. E. A. Ivanova and A. N. Orekhov, “The role of endoplasmic reticulum stress and unfolded protein response in atherosclerosis,” International Journal of Molecular Sciences, vol. 17, no. 2, p. 193, 2016. View at Publisher · View at Google Scholar · View at Scopus
  11. H. Wei, R. Zhang, H. Jin, D. Liu, X. Tang, and C. Tang, “Hydrogen sulfide attenuates hyperhomocysteinemia-induced cardiomyocytic endoplasmic reticulum stress in rats,” Antioxidants & Redox Signaling, vol. 12, no. 9, pp. 1079–1091, 2010. View at Publisher · View at Google Scholar · View at Scopus
  12. S. R. Lentz and J. E. Sadler, “Inhibition of thrombomodulin surface expression and protein C activation by the thrombogenic agent homocysteine,” The Journal of Clinical Investigation, vol. 88, no. 6, pp. 1906–1914, 1991. View at Publisher · View at Google Scholar
  13. X. C. Wang, W. T. Sun, C. M. Yu et al., “ER stress mediates homocysteine-induced endothelial dysfunction: modulation of IKCa and SKCa channels,” Atherosclerosis, vol. 242, no. 1, pp. 191–198, 2015. View at Publisher · View at Google Scholar · View at Scopus
  14. N. Dionisio, I. Jardín, G. M. Salido, and J. A. Rosado, “Homocysteine, intracellular signaling and thrombotic disorders,” Current Medicinal Chemistry, vol. 17, no. 27, pp. 3109–3119, 2015. View at Publisher · View at Google Scholar · View at Scopus
  15. H. Y. Fu, K. Okada, Y. Liao et al., “Ablation of C/EBP homologous protein attenuates endoplasmic reticulum-mediated apoptosis and cardiac dysfunction induced by pressure overload,” Circulation, vol. 122, no. 4, pp. 361–369, 2010. View at Publisher · View at Google Scholar · View at Scopus
  16. M. Wang and R. J. Kaufman, “Protein misfolding in the endoplasmic reticulum as a conduit to human disease,” Nature, vol. 529, no. 7586, pp. 326–335, 2016. View at Publisher · View at Google Scholar · View at Scopus
  17. Q. A. Quick and M. O. Faison, “CHOP and caspase 3 induction underlie glioblastoma cell death in response to endoplasmic reticulum stress,” Experimental and Therapeutic Medicine, vol. 3, no. 3, pp. 487–492, 2012. View at Publisher · View at Google Scholar · View at Scopus
  18. S. Oyadomari, C. Yun, E. A. Fisher et al., “Cotranslocational degradation protects the stressed endoplasmic reticulum from protein overload,” Cell, vol. 126, no. 4, pp. 727–739, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Q. Liu, Z. Chen, and L. X. Chen, “Endoplasmic reticulum stress: a novel mechanism and therapeutic target for cardiovascular diseases,” Acta Pharmacologica Sinica, vol. 37, no. 4, pp. 425–443, 2016. View at Publisher · View at Google Scholar · View at Scopus
  20. P. V. Luoma, “Elimination of endoplasmic reticulum stress and cardiovascular, type 2 diabetic, and other metabolic diseases,” Annals of Medicine, vol. 45, no. 2, pp. 194–202, 2013. View at Publisher · View at Google Scholar · View at Scopus
  21. S. Han, H. Wu, W. Li, and P. Gao, “Protective effects of genistein in homocysteine-induced endothelial cell inflammatory injury,” Molecular and Cellular Biochemistry, vol. 403, no. 1–2, pp. 43–49, 2015. View at Publisher · View at Google Scholar · View at Scopus
  22. D. Wang, H. Wang, P. Luo et al., “Effects of ghrelin on homocysteine-induced dysfunction and inflammatory response in rat cardiac microvascular endothelial cells,” Cell Biology International, vol. 36, no. 6, pp. 511–517, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. H. Mangge, K. Becker, D. Fuchs, and J. M. Gostner, “Antioxidants, inflammation and cardiovascular disease,” World Journal of Cardiology, vol. 6, no. 6, pp. 462–477, 2014. View at Publisher · View at Google Scholar
  24. N. Dionisio, I. Jardín, G. M. Salido, and J. A. Rosado, “Homocysteine, intracellular signaling and thrombotic disorders,” Current Medicinal Chemistry, vol. 17, no. 27, pp. 3109–3119, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. A. Carluccio, M. A. Ancora, M. Massaro et al., “Homocysteine induces VCAM-1 gene expression through NF-kappaB and NAD(P)H oxidase activation: protective role of Mediterranean diet polyphenolic antioxidants,” American Journal of Physiology. Heart and Circulatory Physiology, vol. 293, no. 4, pp. H2344–H2354, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. K. Shi, D. Wang, X. Cao, and Y. Ge, “Endoplasmic reticulum stress signaling is involved in mitomycin C (MMC)-induced apoptosis in human fibroblasts via PERK pathway,” PloS One, vol. 8, no. 12, e59330, 2013. View at Publisher · View at Google Scholar · View at Scopus
  27. L. He, J. Lee, J. H. Jang et al., “Osteoporosis regulation by salubrinal through eIF2alpha mediated differentiation of osteoclast and osteoblast,” Cellular Signalling, vol. 25, no. 2, pp. 552–560, 2013. View at Publisher · View at Google Scholar · View at Scopus
  28. M. Matsuoka and Y. Komoike, “Experimental evidence shows salubrinal, an eIF2alpha dephosphorylation inhibitor, reduces xenotoxicant-induced cellular damage,” International Journal of Molecular Sciences, vol. 16, no. 7, pp. 16275–16287, 2015. View at Publisher · View at Google Scholar · View at Scopus
  29. M. L. Bertoia, J. K. Pai, J. P. Cooke et al., “Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease,” Atherosclerosis, vol. 235, no. 1, pp. 94–101, 2015. View at Publisher · View at Google Scholar · View at Scopus
  30. H. M. Kwon, Y. S. Lee, H. J. Bae, and D. W. Kang, “Homocysteine as a predictor of early neurological deterioration in acute ischemic stroke,” Stroke, vol. 45, no. 3, pp. 871–873, 2014. View at Publisher · View at Google Scholar · View at Scopus
  31. B. Naghshtabrizi, F. Shakerian, M. Hajilooi, and F. Emami, “Plasma homocysteine level and its genotypes as a risk factor for coronary artery disease in patients undergoing coronary angiography,” J Cardiovasc Dis Res, vol. 3, no. 4, pp. 276–279, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. Y. Ji, S. Tan, Y. Xu et al., “Vitamin B supplementation, homocysteine levels, and the risk of cerebrovascular disease: a meta-analysis,” Neurology, vol. 81, no. 15, pp. 1298–12307, 2013. View at Publisher · View at Google Scholar · View at Scopus
  33. K. Mehlig, K. Leander, U. de Faire et al., “The association between plasma homocysteine and coronary heart disease is modified by the MTHFR 677C>T polymorphism,” Heart, vol. 99, no. 23, pp. 1761–1765, 2013. View at Publisher · View at Google Scholar · View at Scopus
  34. L. Papatheodorou and N. Weiss, “Vascular oxidant stress and inflammation in hyperhomocysteinemia,” Antioxidants & Redox Signaling, vol. 9, no. 11, pp. 1941–1958, 2007. View at Publisher · View at Google Scholar · View at Scopus
  35. F. Dong, X. Zhang, S. Y. Li, Z. Zhang, Q. Ren, and B. Culver, “Possible involvement of NADPH oxidase and JNK in homocysteine-induced oxidative stress and apoptosis in human umbilical vein endothelial cells,” Cardiovascular Toxicology, vol. 5, no. 1, pp. 9–20, 2005. View at Google Scholar
  36. G. Topal, A. Brunet, E. Millanvoye et al., “Homocysteine induces oxidative stress by uncoupling of NO synthase activity through reduction of tetrahydrobiopterin,” Free Radical Biology & Medicine, vol. 36, no. 12, pp. 1532–1541, 2004. View at Publisher · View at Google Scholar · View at Scopus
  37. S. H. Kim, K. Y. Kim, S. N. Yu et al., “Silibinin induces mitochondrial NOX4-mediated endoplasmic reticulum stress response and its subsequent apoptosis,” BMC Cancer, vol. 16, p. 452, 2016. View at Publisher · View at Google Scholar · View at Scopus
  38. C. Piccoli, R. Ria, R. Scrima et al., “Characterization of mitochondrial and extra-mitochondrial oxygen consuming reactions in human hematopoietic stem cells. Novel evidence of the occurrence of NAD(P)H oxidase activity,” The Journal of Biological Chemistry, vol. 280, no. 28, pp. 26467–22676, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. H. Wang, X. Jiang, F. Yang et al., “Hyperhomocysteinemia accelerates atherosclerosis in cystathionine betasynthase and apolipoprotein E double knock-out mice with and without dietary perturbation,” Blood, vol. 101, no. 10, pp. 3901–3907, 2003. View at Publisher · View at Google Scholar · View at Scopus
  40. M. A. Hofmann, E. Lalla, Y. Lu et al., “Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model,” The Journal of Clinical Investigation, vol. 107, no. 6, pp. 675–683, 2001. View at Publisher · View at Google Scholar
  41. Z. Xu, G. Lu, and F. Wu, “Simvastatin suppresses homocysteine-induced apoptosis in endothelial cells: roles of caspase-3, cIAP-1 and cIAP-2,” Hypertension Research, vol. 32, no. 5, pp. 375–380, 2009. View at Publisher · View at Google Scholar · View at Scopus
  42. M. Ni and A. S. Lee, “ER chaperones in mammalian development and human diseases,” FEBS Letters, vol. 581, no. 19, pp. 3641–3651, 2007. View at Publisher · View at Google Scholar · View at Scopus
  43. P. Andrew Outinen, S. K. Sood, S. I. Pfeifer et al., “Homocysteine-induced endoplasmic reticulum stress and growth arrest leads to specific changes in gene expression in human vascular endothelial cells,” Blood, vol. 94, no. 3, pp. 959–967, 1999. View at Google Scholar
  44. L. Yin, Y. Dai, Z. Cui, X. Jiang, W. Liu, and F. Han, “The regulation of cellular apoptosis by the ROS-triggered PERK/EIF2α/chop pathway plays a vital role in bisphenol A-induced male reproductive toxicity,” Toxicology and Applied Pharmacology, vol. 314, pp. 98–108, 2016. View at Publisher · View at Google Scholar
  45. L. Li, Q. G. Zhang, L. Y. Lai et al., “Neuroprotective effect of ginkgolide B on bupivacaine-induced apoptosis in SH-SY5Y cells,” Oxidative Medicine and Cellular Longevity, vol. 2013, p. 159864, 2016. View at Publisher · View at Google Scholar · View at Scopus
  46. M. Potente, H. Gerhardt, and P. Carmeliet, “Basic and therapeutic aspects of angiogenesis,” Cell, vol. 146, no. 6, pp. 873–887, 2011. View at Publisher · View at Google Scholar · View at Scopus
  47. C. T. Sibley, T. Estwick, A. Zavodni et al., “Assessment of atherosclerosis in chronic granulomatous disease,” Circulation, vol. 130, no. 23, pp. 2031–2039, 2015. View at Publisher · View at Google Scholar · View at Scopus