Hostname: page-component-586b7cd67f-rcrh6 Total loading time: 0 Render date: 2024-11-26T22:07:58.907Z Has data issue: false hasContentIssue false
  • English
  • Français

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
Get access

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

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

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