Artículos de revistas
Protective Effects Of L-carnitine And Piracetam Against Mitochondrial Permeability Transition And Pc3 Cell Necrosis Induced By Simvastatin
Registro en:
European Journal Of Pharmacology. , v. 701, n. 1/Mar, p. 82 - 86, 2013.
142999
10.1016/j.ejphar.2013.01.001
2-s2.0-84873461054
Autor
Costa R.A.P.
Fernandes M.P.
De Souza-Pinto N.C.
Vercesi A.E.
Institución
Resumen
Mitochondrial oxidative stress followed by membrane permeability transition (MPT) has been considered as a possible mechanism for statins cytotoxicity. Statins use has been associated with reduced risk of cancer incidence, especially prostate cancer. Here we investigated the pathways leading to simvastatin-induced prostate cancer cell death as well as the mechanisms of cell death protection by l-carnitine or piracetam. These compounds are known to prevent and/or protect against cell death mediated by oxidative mitochondrial damage induced by a variety of conditions, either in vivo or in vitro. The results provide evidence that simvastatin induced MPT and cell necrosis were sensitive to either l-carnitine or piracetam in a dose-dependent fashion and mediated by additive mechanisms. When combined, l-carnitine and piracetam acted at concentrations significantly lower than they act individually. These results shed new light into both the cytotoxic mechanisms of statins and the mechanisms underlying the protection against MPT and cell death by the compounds l-carnitine and piracetam. © 2013 Elsevier B.V. All rights reserved. 701 1/Mar 82 86 Barazzoni, R., Zanetti, M., Cappellari, G.G., Semolic, A., Boschelle, M., Codarin, E., Pirulli, A., Guarnieri, G., Fatty acids acutely enhance insulin-induced oxidative stress and cause insulin resistance by increasing mitochondrial reactive oxygen species (ROS) generation and nuclear factor-kappaB inhibitor (IkappaB)-nuclear factor-kappaB (NFkappaB) activation in rat muscle, in the absence of mitochondrial dysfunction (2012) Diabetologia, 55, pp. 773-782 Bhuiyan, J., Seccombe, D.W., The effects of 3-hydroxy-3-methylglutaryl-CoA reductase inhibition on tissue levels of carnitine and carnitine acyltransferase activity in the rabbit (1996) Lipids, 31, pp. 867-870 Binienda, Z., Przybyla-Zawislak, B., Virmani, A., Schmued, L., L-Carnitine and neuroprotection in the animal model of mitochondrial dysfunction (2005) Ann. NY Acad. Sci., 1053, pp. 174-182 Binienda, Z.K., Neuroprotective effects of l-carnitine in induced mitochondrial dysfunction (2003) Ann. NY Acad. Sci., 993 (289-295), pp. 289-345. , (discussion) Brill II, L.B., Bennett Jr., J.P., Dependence on electron transport chain function and intracellular signaling of genomic responses in SH-SY5Y cells to the mitochondrial neurotoxin MPP(+) (2003) Exp. Neurol., 181, pp. 25-38 Campos, C.B., Degasperi, G.R., Pacifico, D.S., Alberici, L.C., Carreira, R.S., Guimaraes, F., Castilho, R.F., Vercesi, A.E., Ibuprofen-induced Walker 256 tumor cell death: Cytochrome c release from functional mitochondria and enhancement by calcineurin inhibition (2004) Biochem. Pharmacol., 68, pp. 2197-2206 Castilho, R.F., Kowaltowski, A.J., Meinicke, A.R., Vercesi, A.E., Oxidative damage of mitochondria induced by Fe(II)citrate or t-butyl hydroperoxide in the presence of Ca2+: Effect of coenzyme Q redox state (1995) Free Radical Biol. Med., 18, pp. 55-59 Collins, R., Armitage, J., Parish, S., Sleigh, P., Peto, R., MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: A randomised placebo-controlled trial (2003) Lancet, 361, pp. 2005-2016 Cook, G.A., Khan, B., Heimberg, M., Feeding of lovastatin to rats increases the activity of the hepatic mitochondrial outer carnitine palmitoyltransferase (1988) Biochem. Biophys. Res. Commun., 150, pp. 1077-1082 Elinos-Calderon, D., Robledo-Arratia, Y., Perez-De La Cruz, V., Pedraza-Chaverri, J., Ali, S.F., Santamaria, A., Early nerve ending rescue from oxidative damage and energy failure by L: -carnitine as post-treatment in two neurotoxic models in rat: Recovery of antioxidant and reductive capacities (2009) Exp. Brain Res., 197, pp. 287-296 Endo, A., The discovery and development of HMG-CoA reductase inhibitors (1992) J. Lipid Res., 33, pp. 1569-1582 Fagian, M.M., Pereira-Da-Silva, L., Martins, I.S., Vercesi, A.E., Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants (1990) J. Biol. Chem., 265, pp. 19955-19960 Figueira, T.R., Barros, M.H., Camargo, A.A., Castilho, R.F., Ferreira, J.C., Kowaltowski, A.J., Sluse, F.E., Vercesi, A.E., Mitochondria as a source of reactiveoxygen and nitrogen species: From molecular mechanisms to human health Antioxid. Redox. Signal, , http://dx.doi.org/10.1089/ars.2012.4729, in press Figueira, T.R., Melo, D.R., Vercesi, A.E., Castilho, R.F., Safranine as a fluorescent probe for the evaluation of mitochondrial membrane potential in isolated organelles and permeabilized cells (2012) Methods Mol. Biol., 810, pp. 103-117 Ghavami, S., Yeganeh, B., Stelmack, G.L., Kashani, H.H., Sharma, P., Cunnington, R., Rattan, S., Halayko, A.J., Apoptosis, autophagy and ER stress in mevalonate cascade inhibition-induced cell death of human atrial fibroblasts (2012) Cell Death Dis., 3, p. 330 Ghosh, S., Kewalramani, G., Yuen, G., Pulinilkunnil, T., An, D., Innis, S.M., Allard, M.F., Rodrigues, B., Induction of mitochondrial nitrative damage and cardiac dysfunction by chronic provision of dietary omega-6 polyunsaturated fatty acids (2006) Free Radical Biol. Med., 41, pp. 1413-1424 Grijalba, M.T., Vercesi, A.E., Schreier, S., Ca2+-induced increased lipid packing and domain formation in submitochondrial particles. A possible early step in the mechanism of Ca 2+-stimulated generation of reactive oxygen species by the respiratory chain (1999) Biochemistry, 38, pp. 13279-13287 Gulcin, I., Antioxidant and antiradical activities of l-carnitine (2006) Life Sci., 78, pp. 803-811 Guzman, M., Cortes, J.P., Castro, J., Effects of lovastatin on hepatic fatty acid metabolism (1993) Lipids, 28, pp. 1087-1093 Hsu, M., Muchova, L., Morioka, I., Wong, R.J., Schroder, H., Stevenson, D.K., Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo (2006) Biochem. Biophys. Res. Commun., 343, pp. 738-744 Hunter, D.R., Haworth, R.A., Southard, J.H., Relationship between configuration, function, and permeability in calcium-treated mitochondria (1976) J. Biol. Chem., 251, pp. 5069-5077 Jun, D.W., Cho, W.K., Jun, J.H., Kwon, H.J., Jang, K.S., Kim, H.J., Jeon, H.J., Lee, M.H., Prevention of free fatty acid-induced hepatic lipotoxicity by carnitine via reversal of mitochondrial dysfunction (2011) Liver Int., 31, pp. 1315-1324 Kaufmann, P., Torok, M., Zahno, A., Waldhauser, K.M., Brecht, K., Krahenbuhl, S., Toxicity of statins on rat skeletal muscle mitochondria (2006) Cell Mol. Life Sci., 63, pp. 2415-2425 Keil, U., Scherping, I., Hauptmann, S., Schuessel, K., Eckert, A., Muller, W.E., Piracetam improves mitochondrial dysfunction following oxidative stress (2006) Br. J. Pharmacol., 147, pp. 199-208 Kim, J.S., Wang, J.H., Lemasters, J.J., Mitochondrial permeability transition in rat hepatocytes after anoxia/reoxygenation: Role of Ca2+-dependent mitochondrial formation of reactive oxygen species (2012) Am. J. Physiol. Gastrointest. Liver Physiol., 302, pp. 723-G731 Kowaltowski, A.J., Castilho, R.F., Vercesi, A.E., Mitochondrial permeability transition and oxidative stress (2001) FEBS Lett., 495, pp. 12-15 Kwak, H.B., Thalacker-Mercer, A., Anderson, E.J., Lin, C.T., Kane, D.A., Lee, N.S., Cortright, R.N., Neufer, P.D., Simvastatin impairs ADP-stimulated respiration and increases mitochondrial oxidative stress in primary human skeletal myotubes (2012) Free Radical Biol. Med., 52, pp. 198-207 Lemasters, J.J., Theruvath, T.P., Zhong, Z., Nieminen, A.L., Mitochondrial calcium and the permeability transition in cell death (2009) Biochim. Biophys. Acta, 1787, pp. 1395-1401 Li, J., Sun, Y.M., Wang, L.F., Li, Z.Q., Pan, W., Cao, H.Y., Comparison of effects of simvastatin versus atorvastatin on oxidative stress in patients with coronary heart disease (2010) Clin. Cardiol., 33, pp. 222-227 Madesh, M., Balasubramanian, K.A., Activation of liver mitochondrial phospholipase A2 by superoxide (1997) Arch. Biochem. Biophys., 346, pp. 187-192 Manfredini, V., Biancini, G.B., Vanzin, C.S., Dal Vesco, A.M., Cipriani, F., Biasi, L., Tremea, R., Vargas, C.R., Simvastatin treatment prevents oxidative damage to DNA in whole blood leukocytes of dyslipidemic type 2diabetic patients (2010) Cell Biochem. Funct., 28, pp. 360-366 Marcella, S.W., David, A., Ohman-Strickland, P.A., Carson, J., Rhoads, G.G., Statin use and fatal prostate cancer: A matched case-control study (2011) Cancer, 118, pp. 4046-4052 Mondul, A.M., Weinstein, S.J., Virtamo, J., Albanes, D., Serum total and HDL cholesterol and risk of prostate cancer (2011) Cancer Causes Control, 22, pp. 1545-1552 Moretti, S., Famularo, G., Marcellini, S., Boschini, A., Santini, G., Trinchieri, V., Lucci, L., De Simone, C., L-Carnitine reduces lymphocyte apoptosis and oxidant stress in HIV-1-infected subjects treated with zidovudine and didanosine (2002) Antioxid. Redox. Signal, 4, pp. 391-403 Nishimura, M., Okimura, Y., Fujita, H., Yano, H., Lee, J., Suzaki, E., Inoue, M., Sasaki, J., Mechanism of 3-nitropropionic acid-induced membrane permeability transition of isolated mitochondria and its suppression by l-carnitine (2008) Cell Biochem. Funct., 26, pp. 881-891 Oliveira, K.A., Zecchin, K.G., Alberici, L.C., Castilho, R.F., Vercesi, A.E., Simvastatin inducing PC3 prostate cancer cell necrosis mediated by calcineurin and mitochondrial dysfunction (2008) J. Bioenerg. Biomembr., 40, pp. 307-314 Panov, A., Dikalov, S., Shalbuyeva, N., Taylor, G., Sherer, T., Greenamyre, J.T., Rotenone model of Parkinson disease: Multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication (2005) J. Biol. Chem., 280, pp. 42026-42035 Payne, C.M., Weber, C., Crowley-Skillicorn, C., Dvorak, K., Bernstein, H., Bernstein, C., Holubec, H., Garewal, H., Deoxycholate induces mitochondrial oxidative stress and activates NF-kappaB through multiple mechanisms in HCT-116 colon epithelial cells (2007) Carcinogenesis, 28, pp. 215-222 Rasola, A., Sciacovelli, M., Pantic, B., Bernardi, P., Signal transduction to the permeability transition pore (2010) FEBS Lett, 584, pp. 1989-1996 Ricchelli, F., Barbato, P., Milani, M., Gobbo, S., Salet, C., Moreno, G., Photodynamic action of porphyrin on Ca2+ influx in endoplasmic reticulum: A comparison with mitochondria (1999) Biochem. J., 338 (PART 1), pp. 221-227 Ruiz-Ramirez, A., Chavez-Salgado, M., Peneda-Flores, J.A., Zapata, E., Masso, F., El-Hafidi, M., High-sucrose diet increases ROS generation, FFA accumulation, UCP2 level, and proton leak in liver mitochondria (2011) Am. J. Physiol. Endocrinol. Metab., 301, pp. 1198-E1207 Sener, G., Paskaloglu, K., Satiroglu, H., Alican, I., Kacmaz, A., Sakarcan, A., L-Carnitine ameliorates oxidative damage due to chronic renal failure in rats (2004) J. Cardiovasc. Pharmacol., 43, pp. 698-705 Shen, W., Liu, K., Tian, C., Yang, L., Li, X., Ren, J., Packer, L., Liu, J., Protective effects of R-alpha-lipoic acid and acetyl-l-carnitine in MIN6 and isolated rat islet cells chronically exposed to oleic acid (2008) J. Cell Biochem., 104, pp. 1232-1243 Shepherd, J., Cobbe, S.M., Ford, I., Isles, C.G., Lorimer, A.R., Macfarlane, P.W., McKillop, J.H., Packard, C.J., Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group (1995) N. Engl. J. Med., 333, pp. 1301-1307 Silva-Adaya, D., Perez-De La Cruz, V., Herrera-Mundo, M.N., Mendoza-Macedo, K., Villeda-Hernandez, J., Binienda, Z., Ali, S.F., Santamaria, A., Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: Antioxidant and neuroprotective effects of l-carnitine (2008) J. Neurochem., 105, pp. 677-689 Sirvent, P., Mercier, J., Vassort, G., Lacampagne, A., Simvastatin triggers mitochondria-induced Ca2+ signaling alteration in skeletal muscle (2005) Biochem. Biophys. Res. Commun., 329, pp. 1067-1075 Solesio, M.E., Saez-Atienzar, S., Jordan, J., Galindo, M.F., Nitropropionioc acid induces autophagy by mitochondrial permeability transition pore formation rather than activation of the mitochondrial fission pathway (2012) Br. J. Pharmacol. Toman, J., Fiskum, G., Influence of aging on membrane permeability transition in brain mitochondria (2011) J. Bioenerg. Biomembr., 43, pp. 3-10 Tonin, A.M., Grings, M., Busanello, E.N., Moura, A.P., Ferreira, G.C., Viegas, C.M., Fernandes, C.G., Wajner, M., Long-chain 3-hydroxy fatty acids accumulating in LCHAD and MTP deficiencies induce oxidative stress in rat brain (2010) Neurochem. Int., 56, pp. 930-936 Vamos, E., Voros, K., Vecsei, L., Klivenyi, P., Neuroprotective effects of l-carnitine in a transgenic animal model of Huntington's disease (2010) Biomed. Pharmacother., 64, pp. 282-286 Vaseva, A.V., Marchenko, N.D., Ji, K., Tsirka, S.E., Holzmann, S., Moll, U.M., P53 opens the mitochondrial permeability transition pore to trigger Necrosis (2012) Cell, 149, pp. 1536-1548 Vercesi, A.E., Dissociation of NAD(P)+-stimulated mitochondrial Ca2+ efflux from swelling and membrane damage (1984) Arch. Biochem. Biophys., 232, pp. 86-91 Virmani, A., Gaetani, F., Binienda, Z., Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: Metabolic inhibitors, MPTP, and methamphetamine (2005) Ann. NY Acad. Sci., 1053, pp. 183-191 Virmani, A., Gaetani, F., Binienda, Z., Xu, A., Duhart, H., Ali, S.F., Role of mitochondrial dysfunction in neurotoxicity of MPP+: Partial protection of PC12 cells by acetyl-l-carnitine (2004) Ann. NY Acad. Sci., 1025, pp. 267-273 Virmani, A., Gaetani, F., Imam, S., Binienda, Z., Ali, S., The protective role of l-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction (2002) Ann. NY Acad. Sci., 965, pp. 225-232 Virmani, A., Gaetani, F., Imam, S., Binienda, Z., Ali, S., Possible mechanism for the neuroprotective effects of l-carnitine on methamphetamine-evoked neurotoxicity (2003) Ann. NY Acad. Sci., 993 (197-207), pp. 198-287. , (Discussion) Yao, D., Shi, W., Gou, Y., Zhou, X., Yee, T., Zhou, Y., Liu, Z., Fatty acid-mediated intracellular iron translocation: A synergistic mechanism of oxidative injury (2005) Free Radical Biol. Med., 39, pp. 1385-1398 Yapar, K., Kart, A., Karapehlivan, M., Atakisi, O., Tunca, R., Erginsoy, S., Citil, M., Hepatoprotective effect of l-carnitine against acute acetaminophen toxicity in mice (2007) Exp. Toxicol. Pathol., 59, pp. 121-128 Ye, J., Li, J., Yu, Y., Wei, Q., Deng, W., Yu, L., L-Carnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway (2010) Regul. Pept., 161, pp. 58-66 Zhang, H., Jia, H., Liu, J., Ao, N., Yan, B., Shen, W., Wang, X., Luo, C., Combined R-alpha-lipoic acid and acetyl-l-carnitine exerts efficient preventative effects in a cellular model of Parkinson's disease (2010) J. Cell Mol. Med., 14, pp. 215-225 Zhou, H., Liu, X., Liu, L., Yang, Z., Zhang, S., Tang, M., Tang, Y., Hu, R., Oxidative stress and apoptosis of human brain microvascular endothelial cells induced by free fatty acids (2009) J. Int. Med. Res., 37, pp. 1897-1903