Browse > Article
http://dx.doi.org/10.4062/biomolther.2018.009

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)
Publication Information
Biomolecules & Therapeutics / v.26, no.2, 2018 , pp. 175-181 More about this Journal
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.
Keywords
CO; PD; Neuroprotection; Nrf2; HO-1; SOD;
Citations & Related Records
Times Cited By KSCI : 1  (Citation Analysis)
연도 인용수 순위
1 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.   DOI
2 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.   DOI
3 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.   DOI
4 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].   DOI
5 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.
6 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.   DOI
7 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.   DOI
8 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.   DOI
9 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.
10 Blandini, F., Armentero, M. T. and Martignoni, E. (2008) The 6-hydroxydopamine model: news from the past. Parkinsonism Relat. Disord. 14, S124-S129.   DOI
11 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.   DOI
12 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.   DOI
13 Halliwell, B. (2006) Oxidative stress and neurodegeneration: where are we now? J. Neurochem. 97, 1634-1658.   DOI
14 Herman, Z. S. (1997) Carbon monoxide: a novel neural messenger or putative neurotransmitter? Pol. J. Pharmacol. 49, 1-4.
15 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.   DOI
16 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.   DOI
17 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.
18 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.   DOI
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.   DOI
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 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.   DOI
22 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.   DOI
23 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.
24 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.   DOI
25 Schipper, H. M. (1999) Glial HO-1 expression, iron deposition and oxidative stress in neurodegenerative diseases. Neurotox. Res. 1, 57-70.   DOI
26 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.   DOI
27 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.   DOI
28 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.   DOI
29 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.   DOI
30 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.   DOI
31 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.   DOI
32 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.   DOI
33 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.   DOI
34 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.   DOI
35 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.   DOI
36 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.
37 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.   DOI
38 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.
39 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.   DOI
40 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.   DOI
41 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.   DOI
42 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.