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Propofol attenuation of hydrogen peroxide-mediated oxidative stress and apoptosis in cultured cardiomyocytes involves haeme oxygenase-1

Published online by Cambridge University Press:  01 May 2008

J.-J. Xu  and
Y.-L. Wang
J.-J. Xu*
Affiliation:
Renmin Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China
Y.-L. Wang
Affiliation:
Zhongnan Hospital of Wuhan University, Department of Anesthesiology, Anesthesiology Research Laboratory, Wuhan, PR China
*
Correspondence to: Jin-Jin Xu, Anesthesiology Research Laboratory, Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China. E-mail: [email protected]; Tel: +86 276 390 3016; Fax: +86 278 805 2260
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Summary

Background and objective

Our aim was to investigate the cytoprotective effect of propofol against hydrogen peroxide (H2O2)-mediated injury and the effects on the haeme oxygenase-1 system, which is a possible new cytoprotective pathway of propofol.

Methods

Primary cultured newborn rat cardiomyocytes were divided into five groups: (1) untreated (Group control); (2) treated with 200 μmol L−1 H2O2 (Group H) and treated with 200 μmol L−1 H2O2 in the presence of propofol (25, 50 and 100 μmol L−1, (3) Group 25P + H, (4) Group 50P + H and (5) Group 100P + H, respectively); added with zinc protoporphyrin IX (ZnPPIX) (10 μmol L−1), a potent inhibitor of haeme oxygenase activity, or SC-3060 (0.2 μL mL−1), a specific synthetic inhibitor of nuclear factor κB. All were incubated for 6 h. The protective effects of propofol were evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide cytotoxicity assay, the concentration of malondialdehyde, superoxide dismutase activity and cell apoptosis by enzyme-linked immunosorbent assay (ELISA). Reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis were used to detect haeme oxygenase-1 expression.

Results

Compared with H2O2, propofol concentrations (ranging from 50 to 100 μmol L−1) significantly increased haeme oxygenase-1 expression and decreased cardiomyocytes apoptosis, accompanied with a decrease in malondialdehyde, but with an increase in superoxide dismutase activity and cell activity (P < 0.05 and P < 0.01, respectively). The protective effects of propofol were mitigated by the addition of ZnPPIX. The addition of SC-3060 reversed propofol-induced haeme oxygenase-1 expression.

Conclusion

Propofol can protect cardiomyocytes against H2O2-mediated cytotoxicity in a dose-dependent manner and increase haeme oxygenase-1 expression, which may partly mediate the cytoprotective effects of propofol.

Keywords

ANAESTHETICS INTRAVENOUSPROPOFOLHYDROGEN PEROXIDEHAEME OXYGENASE-1CARDIAC MYOCYTES
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 5 , May 2008 , pp. 395 - 402
Copyright
Copyright © European Society of Anaesthesiology 2008

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References

1.Droge, W. Free radicals in the physiological control of cell function. Physiol Rev 2002; 82: 47–95.CrossRefGoogle ScholarPubMed
2.Nohl, H, Stolze, K, Napetschnig, S, Ishikawa, T. Is oxidative stress primarily involved in reperfusion injury of the ischemic heart? Free Radic Biol Med 1991; 11: 581–588.CrossRefGoogle ScholarPubMed
3.Josephson, RA, Silverman, HS, Lakatta, EG, Stern, MD, Zweier, JL. Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes. J Biol Chem 1991; 266: 2354–2361.CrossRefGoogle ScholarPubMed
4.Aruoma, OI, Halliwell, B. Superoxide-dependent and ascorbate-dependent formation of hydroxyl radicals from hydrogen peroxide in the presence of iron. Biochem J 1987; 241: 273–278.CrossRefGoogle Scholar
5.Sayin, MM, Ozatamer, O, Taşöz, R et al. Propofol attenuates myocardial lipid peroxidation during coronary artery bypass grafting surgery. Br J Anaesth 2002; 89: 242–246.CrossRefGoogle ScholarPubMed
6.JrCillo, JE, Finn, R. Hemodynamics in elderly coronary artery disease patients undergoing propofol sedation. J Oral Maxillofac Surg 2006; 64: 1338–1342.CrossRefGoogle ScholarPubMed
7.Stratford, N, Murphy, P. Antioxidant activity of propofol in blood from anaesthetized patients. Eur J Anaesthesiol 1998; 15: 158–160.CrossRefGoogle ScholarPubMed
8.Gülçin, I, Alici, HA, Cesur, M. Determination of in vitro antioxidant and radical scavenging activities of propofol. Chem Pharm Bull 2005; 53: 281–285.CrossRefGoogle ScholarPubMed
9.Kokita, N, Hara, A. Propofol attenuates hydrogen-peroxide induced mechanical and metabolic derangements in the isolated rat heart. Anesthesiology 1996; 84: 117–127.CrossRefGoogle ScholarPubMed
10.McDermott, BJ, McWilliams, S, Smyth, K et al. Protection of cardiomyocyte function by propofol during simulated ischemia is associated with a direct action to reduce pro-oxidant activity. J Mol Cell Cardiol 2007; 42: 600–608.CrossRefGoogle ScholarPubMed
11.Li, YC, Ridefelt, P, Wiklund, L, Bjerneroth, G. Propofol induces a lowering of free cytosolic calcium in myocardial cells. Acta Anaesth Scand 1997; 41: 633–638.Google ScholarPubMed
12.Chen, SM, Li, YG, Wang, DM. Study on changes of heme oxygenase-1 expression in patients with coronary heart disease. Clin Cardiol 2005; 28: 197–201.CrossRefGoogle Scholar
13.Aggeli, I-KS, Gaitanaki, C, Beis, I. Involvement of JNKs and p38-MAPK/MSK1 pathways in H2O2-induced upregulation of heme oxygenase-1 mRNA in H9c2. Cell Signal 2006; 18: 1801–1812.CrossRefGoogle ScholarPubMed
14.Sharma, S, Dewald, O, Adrogue, J et al. Induction of antioxidant gene expression in a mouse model of ischemic cardiomyopathy is dependent on reactive oxygen species. Free Radic Biol Med 2006; 40: 2223–2231.CrossRefGoogle Scholar
15.Acquaviva, R, Campisi, A, Murabito, P et al. Propofol attenuates peroxynitrite-mediated DNA damage and apoptosis in cultured astrocytes: an alternative protective mechanism. Anesthesiology 2004; 101: 1363–1371.CrossRefGoogle ScholarPubMed
16.Maines, MD. The heme oxygenase system:a regulator of second messenger gases. Annu Rev Pharmacol Toxicol 1997; 37: 517–554.CrossRefGoogle ScholarPubMed
17.Otterbein, LO, Choi, AMK. Heme oxygenase: colors of defense against cellular stress. Am J Physiol 2000; 279: 1029–1037.Google ScholarPubMed
18.Gong, P, Hu, B, Stewart, D et al. Cobalt induces heme oxygenase-1 expression by a hypoxia-inducible factor-independent mechanism in Chinese hamster ovary cells. J Biol Chem 2001; 276: 27018–27025.CrossRefGoogle ScholarPubMed
19.Simpson, PC, Savion, S. Differentiation of rat myocytes in single cell culture with and without proliferating non myocardial myocytes: cross striation, ultrastructure, and chronotropic response to catecholamines. Circ Res 1982; 50: 101–116.CrossRefGoogle Scholar
20.Bein, B, Renner, J, Caliebe, D et al. Sevoflurane but not propofol preserves myocardial function during minimally invasive direct coronary artery bypass surgery. Anesth Analg 2005; 100: 610–616.CrossRefGoogle Scholar
21.Corcoran, TB, Englel, A, Sakamoto, H et al. The effects of propofol on lipid peroxidation and inflammatory response in elective coronary artery bypass grafting. J Cardiothorac Vasc Anesth 2004; 18: 592–604.CrossRefGoogle ScholarPubMed
22.Xia, Z, Godin, DV, Ansley, DM. Application of high-dose propofol during ischemia improves postischemic function of rat hearts: effects on tissue antioxidant capacity. Can J Physiol Pharmacol 2004; 82: 919–926.CrossRefGoogle ScholarPubMed
23.Kumar, D, Jugdutt, BI. Apoptosis and oxidants in the heart. J Lab Clin Med 2003; 142: 288–297.CrossRefGoogle ScholarPubMed
24.Burlacu, A, Jinga, V, Gafencu, AV, Simionescu, M. Severity of oxidative stress generates different mechanisms of endothelial cell death. Cell Tissue Res 2001; 306: 409–416.CrossRefGoogle ScholarPubMed
25.Rushworth, SA, Chen, XL, Mackman, N, Ogborne, RM, O’Connell, MA. Lipopolysaccharide-induced heme oxygenase-1 expression in human monocytic cells is mediated via Nrf2 and protein kinase C. J Immunol 2005; 175: 4408–4415.CrossRefGoogle ScholarPubMed
26.Terry, CM, Clikeman, JA, Hoidal, JR, Callahan, KS. TNF-α and IL-1α induce heme oxygenase-1 via protein kinase C, Ca2+, and phospholipase A2 in endothelial cells. Am J Physiol 1999; 276: 1493–1501.Google ScholarPubMed
27.Numazawa, S, Ishikawa, M, Yoshida, A, Tanaka, S, Yoshida, T. A typical protein kinase C mediates activation of NF-E2-related factor 2 in response to oxidative stress. Am J Physiol 2003; 285: C334–C342.CrossRefGoogle Scholar
28.Wickley, PJ, Shiga, T, Murray, PA, Damron, DS. Propofol decreases myofilament Ca2+ sensitivity via a protein kinase C-, nitric oxide synthase-dependent pathway in diabetic cardiomyocytes. Anesthesiology 2006; 104: 978–987.CrossRefGoogle Scholar
29.Wickley, PJ, Ding, X, Murray, PA, Damron, DS. Propofol-induced activation of protein kinase C isoforms in adult rat ventricular myocytes. Anesthesiology 2006; 104: 970–977.CrossRefGoogle ScholarPubMed
30.Kanaya, N, Gable, B, Murray, PA, Damron, DS. Propofol increases phosphorylation of troponin I and myosin light chain 2 via protein kinase C activation in cardiomyocytes. Anesthesiology 2003; 98: 1363–1371.CrossRefGoogle ScholarPubMed