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Oleic acid mitigates TNF-α-induced oxidative stress in rat cardiomyocytes

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Abstract

Some of the effects of tumor necrosis factor alpha (TNF-α) are suggested to be mediated by oxidative stress. It has also been reported that dietary supplements of olive oil result in a reduction in LDL, oxidative stress, and blood pressure and these effects are attributed to oleic acid (OA)—a major component of olive oil. The objective of this study was to examine the beneficial effects of OA against TNF-α-induced oxidative stress and cardiomyocytes injury. Isolated cardiomyocytes from adult rat hearts were treated as follows: (A) control; (B) OA (50 μM); (C) TNF-α (10 ng/ml); and (D) TNF-α + OA. After 4 h of the treatment, cells were assessed for oxidative stress, cellular damage, viability, and apoptosis. Cardiomyocytes treated with TNF-α showed a significant increase (P < 0.05) in reactive oxygen species, decrease in the viability of cells, and increase in creatine kinase release. All these TNF-α-induced changes were prevented by OA. TNF-α also caused a significant increase in the expression of apoptotic proteins Bax, Caspase 3 and PARP cleavage, Bnip3, and TGF-β , whereas OA modulated these changes. It is suggested that TNF-α induced oxidative stress mediates cardiomyocyte cell damage which is prevented by OA.

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References

  1. WHO (2011) The top 10 causes of death. In: WHO. http://www.who.int/mediacentre/factsheets/fs310/en/index.html. Accessed 05 Mar 2012

  2. Pfeffer MA, Pfeffer JM, Lamas GA (1993) Development and prevention of congestive heart failure following myocardial infarction. Circulation 87(IV):120–125

    Google Scholar 

  3. Dewald O, Ren G, Duerr GD, Zoerlein M, Klemm C, Gersch C, Tincey S, Michael LH, Entman ML, Frangogiannis NG (2004) Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol 164:665–677

    Article  PubMed  CAS  Google Scholar 

  4. Nian M, Lee P, Khaper N, Liu P (2004) Inflammatory cytokines and postmyocardial infarction remodeling. Circ Res 94:1543–1553

    Article  PubMed  CAS  Google Scholar 

  5. Kaur K, Sharma AK, Singal PK (2006) Significance of changes in TNF-alpha and IL-10 levels in the progression of heart failure subsequent to myocardial infarction. Am J Physiol Heart Circ Physiol 291:H106–H113

    Article  PubMed  CAS  Google Scholar 

  6. de Lorgeril M, Salen P, Martin JL, Monjaud I, Boucher P, Mamelle N (1998) Mediterranean dietary pattern in a randomized trial: prolonged survival and possible reduced cancer rate. Arch Intern Med 158:1181–1187

    Article  PubMed  Google Scholar 

  7. Owen RW, Giacosa A, Hull WE, Haubner R, Wurtele G, Spiegelhalder B, Bartsch H (2000) Olive-oil consumption and health: the possible role of antioxidants. Lancet Oncol 1:107–112

    Article  PubMed  CAS  Google Scholar 

  8. Lowry RR, Tinsley IJ (1966) Oleic and linoleic acid interaction in polyunsaturated fatty acid metabolism in the rat. J Nutr 88:26–32

    PubMed  CAS  Google Scholar 

  9. Herrera MD, Perez-Guerrero C, Marhuenda E, Ruiz-Gutierrez V (2001) Effects of dietary oleic-rich oils (virgin olive and high-oleic-acid sunflower) on vascular reactivity in Wistar–Kyoto and spontaneously hypertensive rats. Br J Nutr 86:349–357

    Article  PubMed  CAS  Google Scholar 

  10. Maguire LS, O’Sullivan SM, Galvin K, O’Connor TP, O’Brien NM (2004) Fatty acid profile, tocopherol, squalene and phytosterol content of walnuts, almonds, peanuts, hazelnuts and the macadamia nut. Int J Food Sci Nutr 55:171–178

    Article  PubMed  CAS  Google Scholar 

  11. Fung TT, Rexrode KM, Mantzoros CS, Manson JE, Willett WC, Hu FB (2009) Mediterranean diet and incidence of and mortality from coronary heart disease and stroke in women. Circulation 119:1093–1100

    Article  PubMed  Google Scholar 

  12. Listenberger LL, Han X, Lewis SE, Cases S, Farese RV Jr, Ory DS, Schaffer JE (2003) Triglyceride accumulation protects against fatty acid-induced lipotoxicity. Proc Natl Acad Sci USA 100:3077–3082

    Article  PubMed  CAS  Google Scholar 

  13. Waterman E, Lockwood B (2007) Active components and clinical applications of olive oil. Altern Med Rev 12:331–342

    PubMed  Google Scholar 

  14. Khodadadi I, Griffin B, Thumser A (2008) Differential effects of long-chain fatty acids and clofibrate on gene expression profiles in cardiomyocytes. Arch Iran Med 11:42–49

    PubMed  CAS  Google Scholar 

  15. Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86

    Article  PubMed  CAS  Google Scholar 

  16. Kirshenbaum LA, Thomas TP, Randhawa AK, Singal PK (1992) Time-course of cardiac myocyte injury due to oxidative stress. Mol Cell Biochem 111:25–31

    Article  PubMed  CAS  Google Scholar 

  17. Dhingra S, Sharma AK, Arora RC, Slezak J, Singal PK (2009) IL-10 attenuates TNF-alpha-induced NF kappaB pathway activation and cardiomyocyte apoptosis. Cardiovasc Res 82:59–66

    Article  PubMed  CAS  Google Scholar 

  18. Swift LM, Sarvazyan N (2000) Localization of dichlorofluorescin in cardiac myocytes: implications for assessment of oxidative stress. Am J Physiol Heart Circ Physiol 278:H982–H990

    PubMed  CAS  Google Scholar 

  19. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem 72:248–254

    Article  PubMed  CAS  Google Scholar 

  20. Yubero-Serrano EM, Delgado-Casado N, Delgado-Lista J, Perez-Martinez P, Tasset-Cuevas I, Santos-Gonzalez M, Caballero J, Garcia-Rios A, Marin C, Gutierrez-Mariscal FM, Fuentes F, Villalba JM, Tunez I, Perez-Jimenez F, Lopez-Miranda J (2011) Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women. Age (Dordr) 33:579–590

    Article  CAS  Google Scholar 

  21. Fuentes F, Lopez-Miranda J, Perez-Martinez P, Jimenez Y, Marin C, Gomez P, Fernandez JM, Caballero J, Delgado-Lista J, Perez-Jimenez F (2008) Chronic effects of a high-fat diet enriched with virgin olive oil and a low-fat diet enriched with alpha-linolenic acid on postprandial endothelial function in healthy men. Br J Nutr 100:159–165

    Article  PubMed  CAS  Google Scholar 

  22. Rallidis LS, Lekakis J, Kolomvotsou A, Zampelas A, Vamvakou G, Efstathiou S, Dimitriadis G, Raptis SA, Kremastinos DT (2009) Close adherence to a Mediterranean diet improves endothelial function in subjects with abdominal obesity. Am J Clin Nutr 90:263–268

    Article  PubMed  CAS  Google Scholar 

  23. Marin C, Ramirez R, Delgado-Lista J, Yubero-Serrano EM, Perez-Martinez P, Carracedo J, Garcia-Rios A, Rodriguez F, Gutierrez-Mariscal FM, Gomez P, Perez-Jimenez F, Lopez-Miranda J (2011) Mediterranean diet reduces endothelial damage and improves the regenerative capacity of endothelium. Am J Clin Nutr 93:267–274

    Article  PubMed  CAS  Google Scholar 

  24. Chrysohoou C, Panagiotakos DB, Aggelopoulos P, Kastorini CM, Kehagia I, Pitsavos C, Stefanadis C (2010) The Mediterranean diet contributes to the preservation of left ventricular systolic function and to the long-term favorable prognosis of patients who have had an acute coronary event. Am J Clin Nutr 92:47–54

    Article  PubMed  CAS  Google Scholar 

  25. Aizawa K, Shoemaker JK, Overend TJ, Petrella RJ (2009) Effects of lifestyle modification on central artery stiffness in metabolic syndrome subjects with pre-hypertension and/or pre-diabetes. Diabetes Res Clin Pract 83:249–256

    Article  PubMed  CAS  Google Scholar 

  26. Esposito K, Ciotola M, Giugliano D (2006) Mediterranean diet, endothelial function and vascular inflammatory markers. Public Health Nutr 9:1073–1076

    Article  PubMed  Google Scholar 

  27. Maury CP, Teppo AM (1989) Circulating tumour necrosis factor-alpha (cachectin) in myocardial infarction. J Intern Med 225:333–336

    Article  PubMed  CAS  Google Scholar 

  28. Squadrito F, Altavilla D, Zingarelli B, Ioculano M, Calapai G, Campo GM, Miceli A, Caputi AP (1993) Tumor necrosis factor involvement in myocardial ischaemia-reperfusion injury. Eur J Pharmacol 237:223–230

    Article  PubMed  CAS  Google Scholar 

  29. De Biase L, Pignatelli P, Lenti L, Tocci G, Piccioni F, Riondino S, Pulcinelli FM, Rubattu S, Volpe M, Violi F (2003) Enhanced TNF alpha and oxidative stress in patients with heart failure: effect of TNF alpha on platelet O2-production. Thromb Haemost 90:317–325

    PubMed  Google Scholar 

  30. Tsutamoto T, Wada A, Matsumoto T, Maeda K, Mabuchi N, Hayashi M, Tsutsui T, Ohnishi M, Sawaki M, Fujii M, Matsumoto T, Yamamoto T, Horie H, Sugimoto Y, Kinoshita M (2001) Relationship between tumor necrosis factor-alpha production and oxidative stress in the failing hearts of patients with dilated cardiomyopathy. J Am Coll Cardiol 37:2086–2092

    Article  PubMed  CAS  Google Scholar 

  31. Scheinfeld N (2004) A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatol Treat 15:280–294

    Article  CAS  Google Scholar 

  32. Orrego CM, Nasir N, Oliveira GH, Flores-Arredondo JH, Cordero-Reyes AM, Loebe M, Youker KA, Torre-Amione G (2011) Cellular evidence of reverse cardiac remodeling induced by cardiac resynchronization therapy. Congest Heart Fail 17:140–146

    Article  PubMed  Google Scholar 

  33. Kubota T, McTiernan CF, Frye CS, Slawson SE, Lemster BH, Koretsky AP, Demetris AJ, Feldman AM (1997) Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ Res 81:627–635

    Article  PubMed  CAS  Google Scholar 

  34. Kaur K, Sharma AK, Dhingra S, Singal PK (2006) Interplay of TNF-alpha and IL-10 in regulating oxidative stress in isolated adult cardiac myocytes. J Mol Cell Cardiol 41:1023–1030

    Article  PubMed  CAS  Google Scholar 

  35. Dhingra S, Sharma AK, Singla DK, Singal PK (2007) p38 and ERK1/2 MAPKs mediate the interplay of TNF-alpha and IL-10 in regulating oxidative stress and cardiac myocyte apoptosis. Am J Physiol Heart Circ Physiol 293:H3524–H3531

    Article  PubMed  CAS  Google Scholar 

  36. Woo CH, Eom YW, Yoo MH, You HJ, Han HJ, Song WK, Yoo YJ, Chun JS, Kim JH (2000) Tumor necrosis factor-alpha generates reactive oxygen species via a cytosolic phospholipase A2-linked cascade. J Biol Chem 275:32357–32362

    Article  PubMed  CAS  Google Scholar 

  37. Ghavami S, Eshraghi M, Kadkhoda K, Mutawe MM, Maddika S, Bay GH, Wesselborg S, Halayko AJ, Klonisch T, Los M (2009) Role of BNIP3 in TNF-induced cell death—TNF upregulates BNIP3 expression. Biochim Biophys Acta 1793:546–560

    Article  PubMed  CAS  Google Scholar 

  38. Kim JY, Kim YJ, Lee S, Park JH (2011) BNip3 is a mediator of TNF-induced necrotic cell death. Apoptosis 16:114–126

    Article  PubMed  CAS  Google Scholar 

  39. Gross A, McDonnell JM, Korsmeyer SJ (1999) BCL-2 family members and the mitochondria in apoptosis. Genes Dev 13:1899–1911

    Article  PubMed  CAS  Google Scholar 

  40. Shinoura N, Yoshida Y, Asai A, Kirino T, Hamada H (1999) Relative level of expression of Bax and Bcl-XL determines the cellular fate of apoptosis/necrosis induced by the overexpression of Bax. Oncogene 18:5703–5713

    Article  PubMed  CAS  Google Scholar 

  41. Yuzefovych L, Wilson G, Rachek L (2010) Different effects of oleate vs. palmitate on mitochondrial function, apoptosis, and insulin signaling in L6 skeletal muscle cells: role of oxidative stress. Am J Physiol Endocrinol Metab 299:E1096–E1105

    Article  PubMed  CAS  Google Scholar 

  42. Amin RH, Mathews ST, Alli A, Leff T (2010) Endogenously produced adiponectin protects cardiomyocytes from hypertrophy by a PPARgamma-dependent autocrine mechanism. Am J Physiol Heart Circ Physiol 299:H690–H698

    Article  PubMed  CAS  Google Scholar 

  43. Massaro M, De Caterina R (2002) Vasculoprotective effects of oleic acid: epidemiological background and direct vascular antiatherogenic properties. Nutr Metab Cardiovasc Dis 12:42–51

    PubMed  CAS  Google Scholar 

  44. Krieglstein J, Kewitz T, Kirchhefer U, Hofnagel O, Weissen-Plenz G, Reinbold M, Klumpp S (2010) Damage of guinea pig heart and arteries by a trioleate-enriched diet and of cultured cardiomyocytes by oleic acid. PLoS ONE 5:e9561

    Article  PubMed  Google Scholar 

  45. Duval C, Auge N, Frisach MF, Casteilla L, Salvayre R, Negre-Salvayre A (2002) Mitochondrial oxidative stress is modulated by oleic acid via an epidermal growth factor receptor-dependent activation of glutathione peroxidase. Biochem J 367:889–894

    Article  PubMed  CAS  Google Scholar 

  46. Harvey KA, Walker CL, Xu Z, Whitley P, Pavlina TM, Hise M, Zaloga GP, Siddiqui RA (2010) Oleic acid inhibits stearic acid-induced inhibition of cell growth and pro-inflammatory responses in human aortic endothelial cells. J Lipid Res 51:3470–3480

    Article  PubMed  CAS  Google Scholar 

  47. de Vries JE, Vork MM, Roemen TH, de Jong YF, Cleutjens JP, van der Vusse GJ, van Bilsen M (1997) Saturated but not mono-unsaturated fatty acids induce apoptotic cell death in neonatal rat ventricular myocytes. J Lipid Res 38:1384–1394

    PubMed  Google Scholar 

  48. Dyntar D, Eppenberger-Eberhardt M, Maedler K, Pruschy M, Eppenberger HM, Spinas GA, Donath MY (2001) Glucose and palmitic acid induce degeneration of myofibrils and modulate apoptosis in rat adult cardiomyocytes. Diabetes 50:2105–2113

    Article  PubMed  CAS  Google Scholar 

  49. Yamasaki M, Tachibana H, Yamada A, Ochi Y, Madhyastha H, Nishiyama K, Yamada K (2008) Oleic acid prevents apoptotic cell death induced by trans10, cis12 isomer of conjugated linoleic acid via p38 MAP kinase dependent pathway. In Vitro Cell Dev Biol Animal 44:290–294

    Article  CAS  Google Scholar 

  50. Katsuma S, Hatae N, Yano T, Ruike Y, Kimura M, Hirasawa A, Tsujimoto G (2005) Free fatty acids inhibit serum deprivation-induced apoptosis through GPR120 in a murine enteroendocrine cell line STC-1. J Biol Chem 280:19507–19515

    Article  PubMed  CAS  Google Scholar 

  51. Dhingra S, Bagchi AK, Ludke AL, Sharma AK, Singal PK (2011) Akt regulates IL-10 mediated suppression of TNFalpha-induced cardiomyocyte apoptosis by upregulating Stat3 phosphorylation. PLoS ONE 6:e25009

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

The study was supported by an operating Grant from the Canadian Institutes of Health Research. P. K. Singal is the holder of the Naranjan S. Dhalla Chair in Cardiovascular Research supported by the St. Boniface Hospital and Research Foundation. Abd Al-Rahman Al-Shudiefat is supported by University of Manitoba Graduate Fellowship/Manitoba Health Research Council Studentship Award.

Conflict of interest

A. Al-Shudiefat, A. Sharma, A. Bagchi, S. Dhingra, and P. Singal have no conflicts of interest.

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Correspondence to Pawan K. Singal.

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Al-Shudiefat, A.A., Sharma, A.K., Bagchi, A.K. et al. Oleic acid mitigates TNF-α-induced oxidative stress in rat cardiomyocytes. Mol Cell Biochem 372, 75–82 (2013). https://doi.org/10.1007/s11010-012-1447-z

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  • DOI: https://doi.org/10.1007/s11010-012-1447-z

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