Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Carbon Monoxide Ameliorates 6-Hydroxydopamine-Induced Cell Death in C6 Glioma Cells

  • Moon, Hyewon (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University) ;
  • Jang, Jung-Hee (Department of Pharmacology, School of Medicine, Keimyung University) ;
  • Jang, Tae Chang (Department of Emergency Medicine, School of Medicine, Daegu Catholic University) ;
  • Park, Gyu Hwan (College of Pharmacy, Research Institute of Pharmaceutical Sciences, Kyungpook National University)
  • Received : 2018.01.18
  • Accepted : 2018.01.22
  • Published : 2018.03.01
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Abstract

Carbon monoxide (CO) is well-known as toxic gas and intrinsic signaling molecule such as neurotransmitter and blood vessel relaxant. Recently, it has been reported that low concentration of CO exerts therapeutic actions under various pathological conditions including liver failure, heart failure, gastric cancer, and cardiac arrest. However, little has been known about the effect of CO in neurodegenerative diseases like Parkinson's disease (PD). To test whether CO could exert a beneficial action during oxidative cell death in PD, we examined the effects of CO on 6-hydroxydopamine (6-OHDA)-induced cell death in C6 glioma cells. Treatment of CO-releasing molecule-2 (CORM-2) significantly attenuated 6-OHDA-induced apoptotic cell death in a dose-dependent manner. CORM-2 treatment decreased Bax/Bcl2 ratio and caspase-3 activity, which had been increased by 6-OHDA. CORM-2 increased phosphorylation of NF-E2-related factor 2 (Nrf2) which is a transcription factor regulating antioxidant proteins. Subsequently, CORM-2 also increased the expression of heme oxygenase-1 and superoxide dismutases (CuZnSOD and MnSOD), which were antioxidant enzymes regulated by Nrf2. These results suggest that CO released by CORM-2 treatment may have protective effects against oxidative cell death in PD through the potentiation of cellular adaptive survival responses via activation of Nrf2 and upregulation of heme oxygenase-1, leading to increasing antioxidant defense capacity.

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References

  1. Babu, D., Leclercq, G., Goossens, V., Remijsen, Q., Vandenabeele, P., Motterlini, R. and Lefebvre, R. A. (2015) Antioxidant potential of CORM-A1 and resveratrol during TNF-alpha/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells. Toxicol. Appl. Pharmacol. 288, 161-178.
  2. Basuroy, S., Leffler, C. W. and Parfenova, H. (2013) CORM-A1 prevents blood-brain barrier dysfunction caused by ionotropic glutamate receptor-mediated endothelial oxidative stress and apoptosis. Am. J. Physiol. Cell Physiol. 304, C1105-C1115. https://doi.org/10.1152/ajpcell.00023.2013
  3. Blandini, F., Armentero, M. T. and Martignoni, E. (2008) The 6-hydroxydopamine model: news from the past. Parkinsonism Relat. Disord. 14, S124-S129. https://doi.org/10.1016/j.parkreldis.2008.04.015
  4. Caumartin, Y., Stephen, J., Deng, J. P., Lian, D., Lan, Z., Liu, W., Garcia, B., Jevnikar, A. M., Wang, H., Cepinskas, G. and Luke, P. P. (2011) Carbon monoxide-releasing molecules protect against ischemia-reperfusion injury during kidney transplantation. Kidney Int. 79, 1080-1089. https://doi.org/10.1038/ki.2010.542
  5. Chapman, J. T., Otterbein, L. E., Elias, J. A. and Choi, A. M. (2001) Carbon monoxide attenuates aeroallergen-induced inflammation in mice. Am. J. Physiol. Lung Cell Mol. Physiol. 281, L209-L216. https://doi.org/10.1152/ajplung.2001.281.1.L209
  6. Chi, P. L., Lin, C. C., Chen, Y. W., Hsiao, L. D. and Yang, C. M. (2015) CO induces Nrf2-dependent heme oxygenase-1 transcription by cooperating with Sp1 and c-Jun in rat brain astrocytes. Mol. Neurobiol. 52, 277-292. https://doi.org/10.1007/s12035-014-8869-4
  7. Choi, Y. K. (2017) Role of carbon monoxide in neurovascular repair processing. Biomol. Ther. (Seoul) doi: 10.4062/biomolther.2017.144 [Epub ahead of print].
  8. Christie, A. E., Fontanilla, T. M., Roncalli, V., Cieslak, M. C. and Lenz, P. H. (2014) Diffusible gas transmitter signaling in the copepod crustacean Calanus finmarchicus: identification of the biosynthetic enzymes of nitric oxide (NO), carbon monoxide (CO) and hydrogen sulfide (H2S) using a de novo assembled transcriptome. Gen. Comp. Endocrinol. 202, 76-86.
  9. Fledderus, J. O. and Goldschmeding, R. (2013) Nrf2 implicated as a novel therapeutic target for renal regeneration after acute kidney injury. Nephrol. Dial. Transplant. 28, 1969-1971. https://doi.org/10.1093/ndt/gft202
  10. Ghattas, M. H., Chuang, L. T., Kappas, A. and Abraham, N. G. (2002) Protective effect of HO-1 against oxidative stress in human hepatoma cell line (HepG2) is independent of telomerase enzyme activity. Int. J. Biochem. Cell Biol. 34, 1619-1628. https://doi.org/10.1016/S1357-2725(02)00097-3
  11. Halliwell, B. (2006) Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658. https://doi.org/10.1111/j.1471-4159.2006.03907.x
  12. Herman, Z. S. (1997) Carbon monoxide: a novel neural messenger or putative neurotransmitter? Pol. J. Pharmacol. 49, 1-4.
  13. Hettiarachchi, N., Dallas, M., Al-Owais, M., Griffiths, H., Hooper, N., Scragg, J., Boyle, J. and Peers, C. (2014) Heme oxygenase-1 protects against Alzheimer's amyloid-beta(1-42)-induced toxicity via carbon monoxide production. Cell Death Dis. 5, e1569. https://doi.org/10.1038/cddis.2014.529
  14. Innamorato, N. G., Rojo, A. I., Garcia-Yague, A. J., Yamamoto, M., de Ceballos, M. L. and Cuadrado, A. (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J. Immunol. 181, 680-689. https://doi.org/10.4049/jimmunol.181.1.680
  15. Jamal Uddin, M., Joe, Y., Kim, S.-K., Jeong, S. O., Ryter, S. W., Pae, H.-O. and Chung, H. T. (2016) IRG1 induced by heme oxygenase-1/carbon monoxide inhibits LPS-mediated sepsis and pro-inflammatory cytokine production. Cell. Mol. Immunol. 13, 170-179. https://doi.org/10.1038/cmi.2015.02
  16. Joshi, G. and Johnson, J. A. (2012) The Nrf2-ARE pathway: a valuable therapeutic target for the treatment of neurodegenerative diseases. Recent Pat. CNS Drug Discov. 7, 218-229.
  17. Kaizaki, A., Tanaka, S., Ishige, K., Numazawa, S. and Yoshida, T. (2006) The neuroprotective effect of heme oxygenase (HO) on oxidative stress in HO-1 siRNA-transfected HT22 cells. Brain Res. 1108, 39-44. https://doi.org/10.1016/j.brainres.2006.06.011
  18. Kalia, L. V. and Lang, A. E. (2016) Parkinson disease in 2015: evolving basic, pathological and clinical concepts in PD. Nat. Rev. Neurol. 12, 65-66. https://doi.org/10.1038/nrneurol.2015.249
  19. Kikuchi, A., Takeda, A., Onodera, H., Kimpara, T., Hisanaga, K., Sato, N., Nunomura, A., Castellani, R. J., Perry, G., Smith, M. A. and Itoyama, Y. (2002) Systemic increase of oxidative nucleic acid damage in Parkinson's disease and multiple system atrophy. Neurobiol. Dis. 9, 244-248. https://doi.org/10.1006/nbdi.2002.0466
  20. Kim, D. S., Chae, S. W., Kim, H. R. and Chae, H. J. (2009) CO and bilirubin inhibit doxorubicin-induced cardiac cell death. Immunopharmacol. Immunotoxicol. 31, 64-70.
  21. Lian, S., Xia, Y., Ung, T. T., Khoi, P. N., Yoon, H. J., Kim, N. H., Kim, K. K. and Jung, Y. D. (2016) Carbon monoxide releasing molecule-2 ameliorates IL-1beta-induced IL-8 in human gastric cancer cells. Toxicology 361-362, 24-38. https://doi.org/10.1016/j.tox.2016.07.003
  22. Magierowski, M., Magierowska, K., Szmyd, J., Surmiak, M., Sliwowski, Z., Kwiecien, S. and Brzozowski, T. (2016) Hydrogen sulfide and carbon monoxide protect gastric mucosa compromised by mild stress against alendronate injury. Dig. Dis. Sci. 61, 3176-3189. https://doi.org/10.1007/s10620-016-4280-5
  23. McCoole, M. D., D'Andrea, B. T., Baer, K. N. and Christie, A. E. (2012) Genomic analyses of gas (nitric oxide and carbon monoxide) and small molecule transmitter (acetylcholine, glutamate and GABA) signaling systems in Daphnia pulex. Comp. Biochem. Physiol. Part D Genomics Proteomics 7, 124-160. https://doi.org/10.1016/j.cbd.2012.01.001
  24. Michiels, C., Raes, M., Toussaint, O. and Remacle, J. (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic. Biol. Med. 17, 235-248. https://doi.org/10.1016/0891-5849(94)90079-5
  25. Mizuguchi, S., Capretta, A., Suehiro, S., Nishiyama, N., Luke, P., Potter, R. F., Fraser, D. D. and Cepinskas, G. (2010) Carbon monoxide-releasing molecule CORM-3 suppresses vascular endothelial cell SOD-1/SOD-2 activity while up-regulating the cell surface levels of SOD-3 in a heparin-dependent manner. Free Radic. Biol. Med. 49, 1534-1541. https://doi.org/10.1016/j.freeradbiomed.2010.08.017
  26. Onyiah, J. C., Sheikh, S. Z., Maharshak, N., Steinbach, E. C., Russo, S. M., Kobayashi, T., Mackey, L. C., Hansen, J. J., Moeser, A. J., Rawls, J. F., Borst, L. B., Otterbein, L. E. and Plevy, S. E. (2013) Carbon monoxide and heme oxygenase-1 prevent intestinal inflammation in mice by promoting bacterial clearance. Gastroenterology 144, 789-798. https://doi.org/10.1053/j.gastro.2012.12.025
  27. Pietrus, M., Paprota, P., Radziszewska, R., Huras, H., Ludwin, A., Wiechec, M., Nocun, A., Ossowski, P., Knafel, A., Kialka, M., Klyszejko-Molska, J., Pitynski, K., Zalustowicz, A. and Banas, T. (2015) Carbon monoxide poisoning in pregnant woman. Przegl Lek 72, 482-484.
  28. Qin, S., Du, R., Yin, S., Liu, X., Xu, G. and Cao, W. (2015) Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation. Inflamm. Res. 64, 537-548.
  29. Ruvolo, P. P., Deng, X., Carr, B. K. and May, W. S. (1998) A functional role for mitochondrial protein kinase Calpha in Bcl2 phosphorylation and suppression of apoptosis. J. Biol. Chem. 273, 25436-25442. https://doi.org/10.1074/jbc.273.39.25436
  30. Schipper, H. M. (1999) Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases. Neurotox. Res. 1, 57-70. https://doi.org/10.1007/BF03033339
  31. Schipper, H. M., Liberman, A. and Stopa, E. G. (1998) Neural heme oxygenase-1 expression in idiopathic Parkinson's disease. Exp. Neurol. 150, 60-68. https://doi.org/10.1006/exnr.1997.6752
  32. Shiraga, H., Pfeiffer, R. F. and Ebadi, M. (1993) The effects of 6-hydroxydopamine and oxidative stress on the level of brain metallothionein. Neurochem. Int. 23, 561-566. https://doi.org/10.1016/0197-0186(93)90104-D
  33. Soni, H., Pandya, G., Patel, P., Acharya, A., Jain, M. and Mehta, A. A. (2011) Beneficial effects of carbon monoxide-releasing molecule-2 (CORM-2) on acute doxorubicin cardiotoxicity in mice: role of oxidative stress and apoptosis. Toxicol. Appl. Pharmacol. 253, 70-80. https://doi.org/10.1016/j.taap.2011.03.013
  34. Suliman, H. B., Carraway, M. S., Ali, A. S., Reynolds, C. M., Welty-Wolf, K. E. and Piantadosi, C. A. (2007) The CO/HO system reverses inhibition of mitochondrial biogenesis and prevents murine doxorubicin cardiomyopathy. J. Clin. Invest. 117, 3730-3741.
  35. Tenhunen, R., Marver, H. S. and Schmid, R. (1968) The enzymatic conversion of heme to bilirubin by microsomal heme oxygenase. Proc. Natl. Acad. Sci. U.S.A. 61, 748-755. https://doi.org/10.1073/pnas.61.2.748
  36. Verma, A., Hirsch, D. J., Glatt, C. E., Ronnett, G. V. and Snyder, S. H. (1993) Carbon monoxide: a putative neural messenger. Science 259, 381-384.
  37. Wegiel, B., Gallo, D., Csizmadia, E., Harris, C., Belcher, J., Vercellotti, G. M., Penacho, N., Seth, P., Sukhatme, V., Ahmed, A., Pandolfi, P. P., Helczynski, L., Bjartell, A., Persson, J. L. and Otterbein, L. E. (2013) Carbon monoxide expedites metabolic exhaustion to inhibit tumor growth. Cancer Res. 73, 7009-7021. https://doi.org/10.1158/0008-5472.CAN-13-1075
  38. Wei, Y., Chen, P., de Bruyn, M., Zhang, W., Bremer, E. and Helfrich, W. (2010) Carbon monoxide-releasing molecule-2 (CORM-2) attenuates acute hepatic ischemia reperfusion injury in rats. BMC Gastroenterol. 10, 42. https://doi.org/10.1186/1471-230X-10-42
  39. Xie, Z., Han, P., Cui, Z., Wang, B., Zhong, Z., Sun, Y., Yang, G., Sun, Q. and Bian, L. (2016) Pretreatment of mouse neural stem cells with carbon monoxide-releasing molecule-2 interferes with NF-${\kappa}B$ p65 signaling and suppresses iron overload-induced apoptosis. Cell. Mol. Neurobiol. 36, 1343-1351. https://doi.org/10.1007/s10571-016-0333-8
  40. Yang, Y. C., Huang, Y. T., Hsieh, C. W., Yang, P. M. and Wung, B. S. (2014) Carbon monoxide induces heme oxygenase-1 to modulate STAT3 activation in endothelial cells via S-glutathionylation. PLoS ONE 9, e100677. https://doi.org/10.1371/journal.pone.0100677
  41. Yao, L., Wang, P., Chen, M., Liu, Y., Zhou, L., Fang, X. and Huang, Z. (2015) Carbon monoxide-releasing molecules attenuate postresuscitation myocardial injury and protect cardiac mitochondrial function by reducing the production of mitochondrial reactive oxygen species in a rat model of cardiac arrest. J. Cardiovasc. Pharmacol. Ther. 20, 330-341. https://doi.org/10.1177/1074248414559837
  42. Zhou, S., Ye, W., Shao, Q., Zhang, M. and Liang, J. (2013) Nrf2 is a potential therapeutic target in radioresistance in human cancer. Crit. Rev. Oncol. Hematol. 88, 706-715. https://doi.org/10.1016/j.critrevonc.2013.09.001

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