Antioxidant properties of myocardial fuels

Molecular and Cellular Biochemistry - Tập 253 Số 1 - Trang 103-111 - 2003
Mallet, Robert T.1, Sun, Jie1
1Department of Integrative Physiology and Cardiovascular Research Institute, University of North Texas Health Science Center, Fort Worth, USA

Tóm tắt

Oxidative metabolism of blood-borne fuels provides myocardium the energy required to sustain its contractile performance. Recent research has revealed that, in addition to supplying energy, certain fuels are able to detoxify harmful oxidants and bolster the myocardium's endogenous antioxidant defenses. These antioxidant capabilities could potentially protect the myocardium from the ravages of reactive oxygen and nitrogen intermediates generated upon reperfusion of ischemic myocardium. This article reviews experimental evidence that two fuels, pyruvate and acetoacetate, provide such antioxidant protection. Pyruvate's antioxidant properties stem in part from its α-keto carboxylate structure, which enables it to directly, non-enzymatically neutralize peroxides and peroxynitrite. Also, citrate, which accumulates in pyruvate-perfused myocardium following anaplerotic pyruvate carboxylation, supports NADPH production to maintain glutathione:glutathione disulfide (GSH/GSSG) redox potential, the central component of the myocardial antioxidant system. Like pyruvate, acetoacetate restores GSH/GSSG and increases contractile function of post-ischemic stunned myocardium, although some of its antioxidant mechanisms may differ from pyruvate's. Both compounds restore β-adrenergic signaling and inotropism, which are compromised in stunned myocardium. N-acetylcysteine, a pharmacological antioxidant that does not provide energy, duplicated the salutary effects of pyruvate and acetoacetate on post-ischemic β-adrenergic signaling and GSH/GSSG. These findings reveal novel, energy-independent mechanisms for enhancement of post-ischemic cardiac performance by metabolic fuels.

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citation_journal_title=Naunyn-Schmiedeberg's Arch Pharmacol; citation_title=Protective effect of N-acetylcysteine on ischaemia-induced myocardial damage in canine heart; citation_author=A Alberola, L Such, F Gil, EJ Zaragoza, EJ Morcillo; citation_volume=343; citation_publication_date=1991; citation_pages=505-510; citation_id=CR1

citation_journal_title=Br J Pharmacol; citation_title=Beneficial effects of N-acetyleysteine and cysteine in stunned myocardium in perfused rat heart; citation_author=L-D Tang, J-Z Sun, K Wu, C-P Sun, Z-M Tang; citation_volume=102; citation_publication_date=1991; citation_pages=601-606; citation_id=CR2

citation_journal_title=Physiol Rev; citation_title=Molecular and cellular mechanisms of myocardial stunning; citation_author=R Bolli, E Marbán; citation_volume=79; citation_publication_date=1999; citation_pages=609-634; citation_id=CR3

citation_journal_title=Mol Cell Biochem; citation_title=Protein nitration; citation_author=W-N Kuo, JM Kreahling, VP Shanbhag, PP Shanbhag, M Mewar; citation_volume=214; citation_publication_date=2000; citation_pages=121-129; citation_id=CR4

citation_journal_title=Cardiovasc Res; citation_title=Status of myocardial antioxidants in ischemia-reperfusion injury; citation_author=NS Dhalla, AB Elmoselhi, T Hata, N Makino; citation_volume=47; citation_publication_date=2000; citation_pages=446-456; citation_id=CR5

citation_journal_title=Free Radic Biol Med; citation_title=Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple; citation_author=FQ Schafer, GR Buettner; citation_volume=30; citation_publication_date=2001; citation_pages=1191-1212; citation_id=CR6

citation_journal_title=Cardiovasc Res; citation_title=The oxygen free radical system: From equations through membrane-protein interactions to cardiovascular injury and protection; citation_author=RC Kukreja, ML Hess; citation_volume=26; citation_publication_date=1992; citation_pages=641-655; citation_id=CR7

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Evidence for a pathogenetic role of xanthine oxidase in the 'stunned' myocardium; citation_author=ML Charlat, PG O'Neill, JM Egan, DR Abernethy, LH Michael, ML Myers, R Roberts, R Bolli; citation_volume=252; citation_publication_date=1987; citation_pages=H566-H577; citation_id=CR8

citation_journal_title=Physiol Rev; citation_title=Cellular defenses against damage from reactive oxygen species; citation_author=BP Yu; citation_volume=74; citation_publication_date=1994; citation_pages=139-162; citation_id=CR9

citation_journal_title=Am J Physiol Cell Physiol; citation_title=Nitric oxide, superoxide, and peroxynitrite: The good, the bad, and the ugly; citation_author=JS Beckman, WH Koppenol; citation_volume=271; citation_publication_date=1996; citation_pages=C1424-C1437; citation_id=CR10

citation_journal_title=J Biol Chem; citation_title=Crystal structure of the antioxidant enzyme glutathione reductase inactivated by peroxynitrite; citation_author=SN Savvides, M Scheiwein, CC Böhme, GE Arteel, PA Karplus, K Becker, RH Schirmer; citation_volume=277; citation_publication_date=2002; citation_pages=2779-2784; citation_id=CR11

citation_journal_title=Arch Biochem Biophys; citation_title=Peroxynitrite-induced membrane lipid peroxidation: The cytotoxic potential of superoxide and nitric oxide; citation_author=R Radi, JS Beckman, KM Bush, BA Freeman; citation_volume=288; citation_publication_date=1991; citation_pages=481-487; citation_id=CR12

citation_journal_title=J Mol Cell Cardiol; citation_title=Glutathione protects against myocardial ischemia-reperfusion injury by detoxifying peroxynitrite; citation_author=P-Y Cheung, W Wang, R Schulz; citation_volume=32; citation_publication_date=2000; citation_pages=1669-1678; citation_id=CR13

citation_journal_title=Neurochem Int; citation_title=Impairment of brain mitochondrial function by reactive nitrogen species: The role of glutathione in dictating susceptibility; citation_author=SJR Heales, JP Bolaños; citation_volume=40; citation_publication_date=2002; citation_pages=469-474; citation_id=CR14

citation_journal_title=Cardiovasc Res; citation_title=Generation of peroxynitrite contributes to ischemia-reperfusion injury in isolated rat hearts; citation_author=W Yasmin, KD Strynadka, R Schulz; citation_volume=33; citation_publication_date=1997; citation_pages=422-432; citation_id=CR15

citation_title=Postischemic myocardial 'stunning': Pathogenesis, pathophysiology, and clinical relevance; citation_inbook_title=Myocardial Protection: The Pathophysiology of Reperfusion and Reperfusion Injury; citation_publication_date=1992; citation_pages=105-149; citation_id=CR16; citation_author=R Bolli; citation_publisher=Raven Press

citation_journal_title=Circ Res; citation_title=Marked reduction of free radical generation and contractile dysfunction by antioxidant therapy begun at the time of reperfusion; citation_author=R Bolli, MO Jeroudi, BS Patel, OI Aruoma, B Halliwell, EK Lai, PB McCay; citation_volume=65; citation_publication_date=1989; citation_pages=607-622; citation_id=CR17

citation_journal_title=Circulation; citation_title=Myocardial free-radical injury after cardioplegia; citation_author=RD Weisel, DAG Mickle, CD Finkle, LC Tumiati, MM Madonik, J Ivanov, GW Burton, KU Ingold; citation_volume=80; citation_issue=supplIII; citation_publication_date=1989; citation_pages=III14-III18; citation_id=CR18

citation_journal_title=J Cell Physiol; citation_title=Hydrogen peroxide-induced oxidative stress to the mammalian heart-muscle cell (cardiomyocyte): Lethal peroxidative membrane injury; citation_author=DR Janero, D Hreniuk, HM Sharif; citation_volume=149; citation_publication_date=1991; citation_pages=347-364; citation_id=CR19

citation_journal_title=Free Radic Res Commun; citation_title=Effects of free radicals on the fluidity of myocardial membranes; citation_author=M Bagchi, MR Prasad, RM Engleman, DK Das; citation_volume=7; citation_publication_date=1989; citation_pages=375-380; citation_id=CR20

citation_journal_title=J Mol Cell Cardiol; citation_title=The effect of primary products of lipid peroxidation on the transmembrane transport of calcium ions; citation_author=AV Lebedev, DO Levitsky, VA Loginov, VN Smirnov; citation_volume=14; citation_issue=suppl3; citation_publication_date=1982; citation_pages=99-103; citation_id=CR21

citation_journal_title=Cardiovasc Res; citation_title=Lipid hydroperoxide modification of proteins during myocardial ischemia; citation_author=P Eaton, DJ Hearse, MJ Shattock; citation_volume=51; citation_publication_date=2001; citation_pages=294-303; citation_id=CR22

citation_journal_title=Eur J Biochem; citation_title=The metabolic consequences of hydroperoxide perfusion on the isolated rat heart; citation_author=JC Chatham, HF Gilbert, GK Radda; citation_volume=184; citation_publication_date=1989; citation_pages=657-662; citation_id=CR23

citation_journal_title=Am J Physiol Cell Physiol; citation_title=Hydroperoxide-induced oxidative stress impairs heart muscle cell carbohydrate metabolism; citation_author=DR Janero, D Hreniuk, HM Sharif; citation_volume=266; citation_publication_date=1994; citation_pages=C179-C188; citation_id=CR24

citation_journal_title=FASEB J; citation_title=Mechanism of peroxide-induced cellular injury in cultured adult cardiac myocytes; citation_author=AA Vlessis, P Muller, D Bartos, D Trunkey; citation_volume=5; citation_publication_date=1991; citation_pages=2600-2605; citation_id=CR25

citation_journal_title=Arch Biochem Biophys; citation_title=Inhibition of mitochondrial electron transport by peroxynitrite; citation_author=R Radi, M Rodriguez, L Castro, R Telleri; citation_volume=308; citation_publication_date=1994; citation_pages=89-95; citation_id=CR26

citation_journal_title=J Neurosci; citation_title=Inhibition of Krebs cycle enzymes by hydrogen peroxide: A key role of α-ketoglutarate dehydrogenase in limiting NADH production under oxidative stress; citation_author=L Tretter, V Adam-Vizi; citation_volume=20; citation_publication_date=2000; citation_pages=8972-8979; citation_id=CR27

citation_journal_title=Basic Res Cardiol; citation_title=Effects of hydrogen peroxide on mitochondrial enzyme function studied in situ in rat heart myocytes; citation_author=T Tatsumi, KJ Kako; citation_volume=88; citation_publication_date=1993; citation_pages=199-211; citation_id=CR28

citation_journal_title=Antioxid Redox Signal; citation_title=Oxygen free radicals and excitation-contraction coupling; citation_author=JI Goldhaber, MS Qayyum; citation_volume=2; citation_publication_date=2000; citation_pages=55-64; citation_id=CR29

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Sarcolemmal Na+,K+-ATPase: Inactivation by neutrophil-derived free radicals and oxidants; citation_author=RC Kukreja, AB Weaver, ML Hess; citation_volume=259; citation_publication_date=1990; citation_pages=H1330-H1336; citation_id=CR30

citation_journal_title=Mol Cell Biochem; citation_title=Inhibition of cardiac sarcolemma Na+-K+ ATPase by oxyradical generating systems; citation_author=Q Shao, T Matsubara, SK Bhatt, NS Dhalla; citation_volume=147; citation_publication_date=1995; citation_pages=139-144; citation_id=CR31

citation_journal_title=J Biol Chem; citation_title=Study of the mechanisms of hydrogen peroxide and hydroxyl free radical-induced cellular injury and calcium overload in cardiac myocytes; citation_author=RA Josephson, HS Silverman, EG Lakatta, MD Stern, JL Zweier; citation_volume=266; citation_publication_date=1991; citation_pages=2354-2361; citation_id=CR32

citation_journal_title=Mech Ageing Dev; citation_title=Enzymatic defenses of the rat heart against lipid peroxidation; citation_author=H Molina, M Garcia; citation_volume=97; citation_publication_date=1997; citation_pages=1-7; citation_id=CR33

citation_journal_title=Arch Biochem Biophys; citation_title=S-glutathiolated hepatocyte proteins and insulin disulfides as substrates for reduction by glutaredoxin, thioredoxin, protein disulfide isomerase, and glutathione; citation_author=CH Jung, JA Thomas; citation_volume=335; citation_publication_date=1996; citation_pages=61-72; citation_id=CR34

citation_journal_title=Biochem Soc Trans; citation_title=Free-radical scavenging activities, interactions and recycling of antioxidants; citation_author=H-J Freislaben, L Packer; citation_volume=21; citation_publication_date=1993; citation_pages=325-330; citation_id=CR35

citation_journal_title=Free Radic Biol Med; citation_title=Cellular reducing equivalents and oxidative stress; citation_author=JP Kehrer, LG Lund; citation_volume=17; citation_publication_date=1994; citation_pages=65-75; citation_id=CR36

citation_journal_title=Proc Soc Exp Biol Med; citation_title=Pyruvate: Metabolic protector of cardiac performance; citation_author=RT Mallet; citation_volume=223; citation_publication_date=2000; citation_pages=136-148; citation_id=CR37

citation_journal_title=Biochim Biophys Acta; citation_title=Energetic modulation of cardiac inotropism and sarcoplasmic reticular Ca2+ uptake; citation_author=RT Mallet, R Bünger; citation_volume=1224; citation_publication_date=1994; citation_pages=22-32; citation_id=CR38

citation_journal_title=Cardiovasc Res; citation_title=Mitochondrial metabolism of pyruvate is required for its enhancement of cardiac function and energetics; citation_author=RT Mallet, J Sun; citation_volume=42; citation_publication_date=1999; citation_pages=149-161; citation_id=CR39

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Pyruvate augments calcium transients in rat ventricular myocytes; citation_author=BJ Martin, HH Valdivia, R Bünger, RD Lasley, RM Mentzer; citation_volume=274; citation_publication_date=1998; citation_pages=H8-H17; citation_id=CR40

citation_journal_title=Circ Res; citation_title=Regulation of the Ca2+ gradient across the sarcoplasmic reticulum in perfused rat heart: A 19F nuclear magnetic resonance study; citation_author=W Chen, R London, E Murphy, C Steenbergen; citation_volume=83; citation_publication_date=1998; citation_pages=898-907; citation_id=CR41

citation_journal_title=J Thorac Cardiovasc Surg; citation_title=Myocardial stunning: A therapeutic conundrum; citation_author=Z Zhou, RD Lasley, JO Hegge, R Bünger, RM Mentzer; citation_volume=110; citation_publication_date=1995; citation_pages=1391-1401; citation_id=CR42

citation_journal_title=Circulation; citation_title=Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy; citation_author=J Zhang, C Toher, M Erhard, Y Zhang, K Ugurbil, RJ Bache, T Lange, DC Homans; citation_volume=96; citation_publication_date=1997; citation_pages=334-343; citation_id=CR43

citation_journal_title=J Mol Cell Cardiol; citation_title=Pyruvate potentiates β-adrenergic inotropism of stunned guinea-pig myocardium; citation_author=MI Tejero-Taldo, J Sun, JL Caffrey, RT Mallet; citation_volume=30; citation_publication_date=1998; citation_pages=2327-2339; citation_id=CR44

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Mechanisms mediating responsiveness to beta-adrenergic stimulation after coronary reperfusion in conscious dogs; citation_author=K Kiuchi, YT Shen, SF Vatner, DE Vatner; citation_volume=267; citation_publication_date=1994; citation_pages=H1578-H1588; citation_id=CR45

citation_journal_title=J Mol Cell Cardiol; citation_title=β-adrenoceptor-linked signal transduction in ischemic-reperfused heart and scavenging of oxyradicals; citation_author=S Persad, S Takeda, V Panagia, NS Dhalla; citation_volume=29; citation_publication_date=1997; citation_pages=545-558; citation_id=CR46

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Modification of cardiac β-adrenoceptor mechanisms by H2O2 ; citation_author=S Persad, H Rupp, R Jindal, J Arneja, NS Dhalla; citation_volume=274; citation_publication_date=1998; citation_pages=H416-H423; citation_id=CR47

citation_journal_title=J Mol Cell Cardiol; citation_title=Antioxidant properties of pyruvate mediate its potentiation of β-adrenergic inotropism in stunned myocardium; citation_author=MI Tejero-Taldo, JL Caffrey, J Sun, RT Mallet; citation_volume=31; citation_publication_date=1999; citation_pages=1863-1872; citation_id=CR48

citation_journal_title=Anal Biochem; citation_title=Nonenzymatic decarboxylation of pyruvate; citation_author=G Constantopoulos, JA Barranger; citation_volume=139; citation_publication_date=1984; citation_pages=353-358; citation_id=CR49

citation_journal_title=Chem Res Toxicol; citation_title=Peroxynitrite-mediated decarboxylation of pyruvate to both carbon dioxide and carbon dioxide radical anion; citation_author=J Vásquez-Vivar, A Denicola, R Radi, O Augusto; citation_volume=10; citation_publication_date=1997; citation_pages=786-794; citation_id=CR50

citation_journal_title=J Biol Chem; citation_title=A 13C mass isotopomer study of anaplerotic pyruvate carboxylation in perfused rat hearts; citation_author=B Comte, G Vincent, B Bouchard, M Jetté, S Cordeau, C Des Rosiers; citation_volume=272; citation_publication_date=1997; citation_pages=26125-26131; citation_id=CR51

citation_journal_title=Biochem J; citation_title=Pyruvate carboxylation as an anaplerotic mechanism in the isolated perfused rat heart; citation_author=KJ Peuhkurinen, IE Hassinen; citation_volume=202; citation_publication_date=1982; citation_pages=67-76; citation_id=CR52

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Pyruvate carboxylation prevents the decline in contractile function of rat hearts oxidizing acetoacetate; citation_author=RR Russell, H Taegtmeyer; citation_volume=261; citation_publication_date=1991; citation_pages=H1756-H1762; citation_id=CR53

citation_journal_title=Nature; citation_title=Citrate as an intermediary in the inhibition of phosphofructokinase in rat heart muscle by fatty acids, ketone bodies, pyruvate, diabetes and starvation; citation_author=PB Garland, PJ Randle, EA Newsholme; citation_volume=200; citation_publication_date=1963; citation_pages=169-170; citation_id=CR54

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Pyruvate potentiates inotropic effects of isoproterenol and Ca2+ in rabbit cardiac muscle preparations; citation_author=HP Hermann, O Zeitz, B Keweloh, G Hasenfuss, PM Janssen; citation_volume=279; citation_publication_date=2000; citation_pages=H702-H708; citation_id=CR55

citation_journal_title=Cardiovasc Res; citation_title=Potentiation of beta-adrenergic inotropic response by pyruvate in failing human myocardium; citation_author=HP Hermann, O Zeitz, SE Lehnart, B Keweloh, N Datz, G Hasenfuss, PM Janssen; citation_volume=53; citation_publication_date=2002; citation_pages=116-123; citation_id=CR56

citation_journal_title=J Mol Cell Cardiol; citation_title=Acetoacetate restores contractile performance and antioxidant potential of H2O2-injured myocardium; citation_author=J Sun, J Squires, RT Mallet; citation_volume=33; citation_publication_date=2001; citation_pages=A115; citation_id=CR57

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Acetoacetate augments β-adrenergic inotropism of stunned myocardium by an antioxidant mechanism; citation_author=JE Squires, J Sun, JL Caffrey, D Yoshishige, RT Mallet; citation_volume=284; citation_publication_date=2003; citation_pages=H1340-H1347; citation_id=CR58

citation_journal_title=Am J Physiol Heart Circ Physiol; citation_title=Energy provision from glycogen, glucose, and fatty acids on adrenergic stimulation of isolated working rat hearts; citation_author=GW Goodwin, F Ahmad, T Doenst, H Taegtmeyer; citation_volume=274; citation_publication_date=1998; citation_pages=H1239-H1247; citation_id=CR59

citation_journal_title=Biochem Biophys Res Commun; citation_title=Carbon dioxide catalysis of the reaction of peroxynitrite with ethyl acetoacetate: An example of aliphatic nitration with peroxynitrite; citation_author=RM Uppu, WA Pryor; citation_volume=229; citation_publication_date=1996; citation_pages=764-769; citation_id=CR60

citation_journal_title=Eur J Biochem; citation_title=Regulation of acetoacetyl-CoA in isolated perfused rat hearts; citation_author=LA Menahan, WT Hron; citation_volume=119; citation_publication_date=1981; citation_pages=295-299; citation_id=CR61

citation_journal_title=J Biochem; citation_title=Significance of catalase in peroxisomal fatty acyl-CoA β-oxidation: NADH oxidation by acetoacetyl-CoA and H2O2 ; citation_author=F Hashimoto, H Hayashi; citation_volume=108; citation_publication_date=1990; citation_pages=426-431; citation_id=CR62

citation_journal_title=Eur J Biochem; citation_title=Glucose requirement for post-ischemic recovery of perfused working heart; citation_author=RT Mallet, DA Hartman, R Bünger; citation_volume=188; citation_publication_date=1990; citation_pages=481-493; citation_id=CR63

citation_journal_title=Basic Res Cardiol; citation_title=On the inability of ketone bodies to serve as the only energy providing substrate for rat heart at physiological work load; citation_author=H Taegtmeyer; citation_volume=78; citation_publication_date=1983; citation_pages=435-450; citation_id=CR64

citation_journal_title=J Biol Chem; citation_title=Regulation of cAMP-dependent protein kinase activity by glutathionylation; citation_author=KM Humphries, C Juliano, SS Taylor; citation_volume=277; citation_publication_date=2002; citation_pages=43505-43511; citation_id=CR65

citation_journal_title=Lancet; citation_title=Haemodynamic effects of intracoronary pyruvate in patients with congestive heart failure: An open study; citation_author=H-P Hermann, B Pieske, E Schwarzmüller, J Keul, H Just, G Hasenfuss; citation_volume=353; citation_publication_date=1999; citation_pages=1321-1323; citation_id=CR66

Olivencia-Yurvati AH, Blair JL, Baig M, Mallet RT: Pyruvate-enhanced cardioprotection during cardiopulmonary bypass surgery. J Cardiothorac Vasc Anesth (in press)