Mitochondrial Electron Transport can Become a Significant Source of Oxidative Injury in Cardiomyocytes
Abstract
Ischemia/reperfusion causes oxidant injury in isolated cardiomyocytes without neutrophils or xanthine oxidase. Since these cells contain mitochondria, we hypothesized that the mitochondrial electron transport chain (ETC) causes this injury. To test this, we altered two conditions known to change within the mitochondria during ischemia/reperfusion-the extent of ETC redox-reduction and oxygen levels-and measured the resulting oxidant generation and injury. Specifically, we exposed cardiomyocytes for 1 h to the mitochondrial ETC inhibitors cyanide, antimycin, and rotenone and measured oxidant generation, using the intracellular fluorescent probe 2',7'-dichlorofluorescin (DCFH, sensitive to H2O2 and hydroxyl radicals). Inhibitors causing more extensive redox-reduction of the ETC (cyanide or antimycin) generated more oxidants than did partial ETC reduction with the inhibitor rotenone (10-fold v five-fold increases in DCFH oxidation). In addition, the DCFH oxidation caused by cyanide could be completely attenuated by the antioxidants 2-mercaptopropionylglycine (MPG) and 1,10 phenanthroline (PHEN). Finally, we tested the relevance of this oxidant generation on cell survival and contraction, with and without antioxidant interventions. Cell viability and contraction after 3-h recovery from cyanide exposure was significantly improved by either the addition of antioxidants, or by the "antioxidant" strategy of lowering O2 levels (i.e. from 150 to 3 tau) during the cyanide exposure (13.8% death with hypoxic cyanide v 48.6% cell death with normoxic cyanide). Collectively, these findings demonstrate that mitochondrial ETC carriers can cause significant oxidant injury, greatest when fully redox-reduced and exposed to oxygen, conditions known to occur in the transition from ischemia to reperfusion.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
PGC-1α, a major regulator of oxidative metabolism and mitochondrial biogenesis, is believed to regulate the mitochondrial antioxidant defense system.
“For example, a transcriptional coactivator, (PPAR)-γ coactivator 1-α (PGC-1α), a major regulator of oxidative metabolism and mitochondrial biogenesis, is believed to regulate the mitochondrial antioxidant defense system (153, 312).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [312]
Cited by
Sorted by citations
Vanden Hoek, T. L., Becker, L. B., Shao, Z., Li, C., & Schumacker, P. T. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.29.18092 · Cited by 721 · see citing works
Self-citationNew concepts in reactive oxygen species and cardiovascular reperfusion physiology
Becker, L. C. (2003) · Cardiovascular Research · doi:10.1016/j.cardiores.2003.10.025 · Cited by 703 · see citing works
“No difference is seen after only 1 h of ischemia (from Vanden Hoek et al. [ 21 ]).”
BackgroundSelf-citationStowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471 · see citing works
“Tissue damage during hypoxia and reperfusion after ischemia has long been known to be associated with increased levels of various ROS (6, 15, 19, 123, 170, 290, 309, 318).”
BackgroundThe Cytochrome bc1 Complex: Function in the Context of Structure
Crofts, A. R. (2004) · Annual Review of Physiology · doi:10.1146/annurev.physiol.66.032102.150251 · Cited by 474 · see citing works
Generation of superoxide in cardiomyocytes during ischemia before reperfusion
Becker, L. B., Hoek, T. L. V., Shao, Z., Li, C., & Schumacker, P. T. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.6.h2240 · Cited by 413 · see citing works
“Multiple sources of oxidant generation could function during ischemia, although a likely source is the mitochondria (4, 29, 30, 33).”
BackgroundSelf-citationRegulation of Yeast Chronological Life Span by TORC1 via Adaptive Mitochondrial ROS Signaling
Pan, Y., Schroeder, E. A., Ocampo, A., Barrientos, A., & Shadel, G. S. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.018 · Cited by 313 · see citing works
“Upon oxidation, DHE intercalates into proximal nucleic acids (usually DNA) to generate a fluorescent signal (Vanden Hoek et al., 1997; Benov et al., 1998).”
BackgroundPreconditioning in Cardiomyocytes Protects by Attenuating Oxidant Stress at Reperfusion
Hoek, T. L. V., Becker, L. B., Shao, Z., Li, C., & Schumacker, P. T. (2000) · Circulation Research · doi:10.1161/01.res.86.5.541 · Cited by 312 · see citing works
Self-citationBrown, G. C., & Borutaitė, V. (2011) · Mitochondrion · doi:10.1016/j.mito.2011.02.001 · Cited by 280 · see citing works
“Some researchers have tried to estimate the contribution of mitochondria to cellular ROS production by measuring some marker of the latter in cells, and then inhibiting the mitochondrial respiratory chain or making cells hypoxic (Dawson et al. 1993; Duranteau et al. 1998; Vanden Hoek et al. 1997).”
BackgroundMechanisms of Cardioprotection by Volatile Anesthetics
Tanaka, K., Ludwig, L. M., Kersten, J. R., Pagel, P. S., & Warltier, D. C. (2004) · Anesthesiology · doi:10.1097/00000542-200403000-00035 · Cited by 274 · see citing works
“respiratory chain have been shown to play important roles during IPC or pharmacologic preconditioning.(111,160,179,180) The complex III inhibitor myxothiazol blocked hypoxia-(160) or acetylcholine-induced(179) ROS generation and abolished”
BackgroundKevin, L. G., Camara, A. K. S., Riess, M. L., Novalija, E., & Stowe, D. F. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00711.2002 · Cited by 272 · see citing works
“In one study, the mKATP channel opener nicorandil enhanced postischemic supply of high-energy phosphates and decreased oxidant injury (35); both factors are consistent with improved ETC function and with evidence that the mitochondrion is the most likely source of ROS during ischemia (44, 47).”
BackgroundWerner, E., & Werb, Z. (2002) · The Journal of Cell Biology · doi:10.1083/jcb.200111028 · Cited by 252 · see citing works
Intracellular generation of reactive oxygen species by mitochondria
Nohl, H., Gille, L., & Staniek, K. (2005) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.12.002 · Cited by 251 · see citing works
Mitochondria: a target for myocardial protection
Suleiman, M. S. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00102-9 · Cited by 251 · see citing works
Cook, S. A., Sugden, P. H., & Clerk, A. (1999) · Circulation Research · doi:10.1161/01.res.85.10.940 · Cited by 248 · see citing works
Oxidative pathways in cardiovascular disease: roles, mechanisms, and therapeutic implications
Wattanapitayakul, S. K. (2001) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(00)00114-5 · Cited by 239 · see citing works
“Several experi- mental hypoxia or ischemia/reperfusion models, both in vitro and in vivo, have suggested that injury in the myo- cardium is caused by oxygen radicals from mitochondrial electron transport (Lesnefsky et al., 1997; Vanden Hoek et al., 1997, 1998).”
BackgroundMitochondrial Medicine: Pharmacological targeting of mitochondria in disease
Armstrong, J. S. (2007) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0707288 · Cited by 235 · see citing works
“The mechanism of ROS production during ischaemia has been suggested to depend on residual low oxygen levels in the presence of a reduced ETC (Vanden Hoek et al., 1997).”
BackgroundCocco, T., Di, M., Papa, P., & Lorusso, M. P. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00034-9 · Cited by 228 · see citing works
Cell death during ischemia: relationship to mitochondrial depolarization and ROS generation
Levraut, J., Iwase, H., Shao, Z. H., Hoek, T. L. V., & Schumacker, P. T. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00708.2002 · Cited by 226 · see citing works
“During ischemia, indexes of oxidant stress were attenuated by mitochondrial electron transport inhibitors, suggesting that the ROS are generated by mitochondria (2, 33, 34).”
BackgroundSelf-citationPotential Therapeutic Benefits of Strategies Directed to Mitochondria
Camara, A. K. S., Lesnefsky, E. J., & Stowe, D. F. (2009) · Antioxidants and Redox Signaling · doi:10.1089/ars.2009.2788 · Cited by 195 · see citing works
“This subject is discussed in greater detail in our recent review article (543), and by others (14, 591, 592), and will not be covered in any more detail here.”
BackgroundÖzcan, C., Bienengraeber, M., Dzeja, P. P., & Terzic, A. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00552.2001 · Cited by 195 · see citing works
“Although SOD-catalase could scavenge ROS that cross mitochondrial membranes as well as ROS directly from generating sites in injury-permeabilized mitochondria (4, 26, 42, 55), the mechanism responsible for reduction of ROS generation by potassium channel openers remains unknown.”
BackgroundZhang, H. J., Zhao, W., Venkataraman, S., Robbins, M. E. C., Buettner, G. R., Kregel, K. C., & Oberley, L. W. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m109801200 · Cited by 179 · see citing works
Penna, C. R. R., Perrelli, M.-G., & Pagliaro, P. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4459 · Cited by 182 · see citing works
“Although ROS are produced by several extracellular and intracellular processes, in cardiomyocytes, mitochondria represent the most relevant site for ROS formation (91, 238, 363–365).”
InfluentialAntioxidant effects of ginsenoside Re in cardiomyocytes
Xie, J.-T., Shao, Z., Hoek, T. L. V., Chang, W., Li, J., Mehendale, S. R., Wang, C., Hsu, C.-W., Becker, L. B., Yin, J., et al. (2006) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2006.01.001 · Cited by 178 · see citing works
Self-citationThe polymorphic and contradictory aspects of intermittent hypoxia
Almendros, I., Wang, Y., & Gozal, D. (2014) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00089.2014 · Cited by 174 · see citing works
Thengchaisri, N., & Kuo, L. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00487.2003 · Cited by 161 · see citing works
Baicalein attenuates oxidant stress in cardiomyocytes
Shao, Z., Hoek, T. L. V., Qin, Y., Becker, L. B., Schumacker, P. T., Li, C., Dey, L., Barth, E. D., Halpern, H. J., Rosen, G. M., et al. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00163.2001 · Cited by 148 · see citing works
“, increases in DCF fluorescence) suggest H2O2 or hydroxyl radical generation (36).”
BackgroundMethodResultInfluentialSelf-citationExtract from Scutellaria baicalensis Georgi Attenuates Oxidant Stress in Cardiomyocytes
Shao, Z., Li, C., Hoek, T. L. V., Becker, L. B., Schumacker, P. T., Wu, J. A., Attele, A. S., & Yuan, C.-S. (1999) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1999.1021 · Cited by 139 · see citing works
Self-citationNitrite Reduction and Cardiovascular Protection
Omar, S. A., & Webb, A. J. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.01.012 · Cited by 121 · see citing works
Aronis, A., Madar, Z., & Tirosh, O. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.01.015 · Cited by 119 · see citing works
Riess, M. (2004) · Cardiovascular Research · doi:10.1016/j.cardiores.2003.09.016 · Cited by 118 · see citing works
State of the Art in Therapeutic Hypothermia
Lampe, J. W., & Becker, L. B. (2010) · Annual Review of Medicine · doi:10.1146/annurev-med-052009-150512 · Cited by 118 · see citing works
Self-citationChen, H., & Yan, X. (2004) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2004.11.016 · Cited by 115 · see citing works
Zhao, D., Abella, B. S., Beiser, D. G., et al. (2007) · Resuscitation · doi:10.1016/j.resuscitation.2007.10.015 · Cited by 113 · see citing works
Self-citationAllyl alcohol and garlic (Allium sativum) extract produce oxidative stress in Candida albicans
Lemar, K. M., Passa, O., Aon, M. A., Cortassa, S. C., Müller, C. T., Plummer, S. F., O'Rourke, B. P., & Lloyd, D. (2005) · Microbiology · doi:10.1099/mic.0.28095-0 · Cited by 108 · see citing works
“Oxidation of CM-H2DCFH by ROS, particularly by hydrogen peroxide (H2O2) and hydroxyl radical (Vanden Hoek et al., 1997a, b), yields the fluorescent product carboxymethyldichlorofluorescein (CM-DCF), and indirectly measures mitochondrially produced O{2 that has dismutated to H2O2 through the action…”
BackgroundNovalija, E., Varadarajan, S. G., Camara, A. K. S., An, J., Chen, Q., Riess, M. L., Hogg, N., & Stowe, D. F. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01056.2001 · Cited by 105 · see citing works
“Major sources of ROS are believed to be NAD(P)H oxidases, other mitochondrial oxidases (primarily complexes I and III), xanthine oxidase, cyclooxygenaselipoxygenase, cytochrome P-450, and uncoupled NO synthase (9, 13, 36, 38, 40).”
BackgroundTargeting nucleotide-requiring enzymes: implications for diazoxide-induced cardioprotection
Dzeja, P. P., Bast, P., Özcan, C., Valverde, A. M., Holmuhamedov, E., Wylen, D. G. L. V., & Terzic, A. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00847.2002 · Cited by 104 · see citing works
“However, excessive succinate oxidation, which occurs on reoxygenation after ischemia as succinate accumulates (70), could be a major source of ROS and tissue damage (7, 30, 67).”
BackgroundInfluentialMitochondrial and cytosolic sources of hydrogen peroxide in resting C2C12 myoblasts
Wong, H. S., Benoit, B., & Brand, M. D. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.10.448 · Cited by 102 · see citing works
Skeletal Muscle Oxidative Capacity, Fiber Type, and Metabolites after Lung Transplantation
WANG, X. N., Williams, T. J., McKenna, M. J., Li, J. L., Fraser, S. F., Side, E. A., SNELL, G. I., Walters, E. H., & CAREY, M. F. (1999) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/ajrccm.160.1.9805092 · Cited by 97 · see citing works
“In addition, the impaired mitochondrial electron transport in vitro could be a source of free radicals, which have been demonstrated to cause loss of contractile function and accelerated cell death in cardiomyocytes ( 29 ).”
BackgroundMitochondria in cardiomyocyte Ca2+ signaling
Lukyanenko, V. I., Chikando, A. C., & Lederer, W. J. (2009) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2009.03.011 · Cited by 95 · see citing works
Shao, Z.-H., Xie, J.-T., Hoek, T. L. V., et al. (2003) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2003.12.001 · Cited by 96 · see citing works
Self-citationXu, M., Wang, Y., Ayub, A., et al. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.3.h1295 · Cited by 94 · see citing works
“The impaired mitochondrial function after I/R is due to imbalance of cytosolic ions, electron transport, production of free radicals, and alteration of membrane potential (15, 28, 32), eventually leading to apoptosis in the ischemic myocardium (2, 5, 29).”
BackgroundAdenosine produces nitric oxide and prevents mitochondrial oxidant damage in rat cardiomyocytes
Xu, Z., PARK, S., Mueller, R. A., Bagnell, R. C., Patterson, C., & Boysen, P. G. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.12.004 · Cited by 93 · see citing works
“In isolated cardiomyocytes subjected to ischemia–reperfusion, the mitochondrial electron transport chain is the main source of ROS upon reperfusion [43].”
BackgroundReperfusion, not simulated ischemia, initiates intrinsic apoptosis injury in chick cardiomyocytes
Hoek, T. L. V., Qin, Y., Wojcik, K., Li, C., Shao, Z., Anderson, T., Becker, L. B., & Hamann, K. J. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00132.2002 · Cited by 90 · see citing works
“As part of functional viability, cell contractions were assessed by observing movement within the same field of cells as previously reported (33).”
BackgroundMethodSelf-citationStarnes, J. W., Barnes, B. D., & Olsen, M. E. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00849.2006 · Cited by 87 · see citing works
“Succinate accumulates in the heart during ischemia (51), and its excessive oxidation on reoxygenation is considered a major source of ROS and tissue damage following ischemia (30, 41, 49).”
Narayan, P., Mentzer, R. M., & Lasley, R. D. (2001) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1282 · Cited by 88 · see citing works
Sedlić, F., Šepac, A., Pravdić, D., Camara, A. K. S., Bienengraeber, M., Brzezinska, A. K., Wakatsuki, T., & Bosnjak, Z. J. (2010) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00006.2010 · Cited by 83 · see citing works
Lemar, K. M., Aon, M. A., Cortassa, S. C., O'Rourke, B. P., Müller, C. T., & Lloyd, D. (2007) · Yeast · doi:10.1002/yea.1503 · Cited by 80 · see citing works
Grape seed proanthocyanidin extract attenuates oxidant injury in cardiomyocytes
Shao, Z. (2003) · Pharmacological Research · doi:10.1016/s1043-6618(03)00041-0 · Cited by 80 · see citing works
Self-citationRegulation of Cellular Gas Exchange, Oxygen Sensing, and Metabolic Control
Clanton, T. L., Hogan, M. C., & Gladden, L. B. (2013) · Comprehensive physiology · doi:10.1002/cphy.c120030 · Cited by 88 · see citing works
Han, F., Da, T., Galdo, N. A. R., & Becker, L. B. (2008) · Critical Care Medicine · doi:10.1097/ccm.0b013e31818a8a51 · Cited by 77 · see citing works
“Significant ROS leakage at complex III, a surrogate for dysfunction, has also been extensively observed with progressive myocardial ischemia (24) and was prominent in our own prior cellular models of simulated ischemia/reperfusion (25).”
BackgroundSelf-citationHan, H. J., Long, H., Wang, H., Wang, J., Zhang, Y., & Wang, Z. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00199.2003 · Cited by 73 · see citing works
“Although the importance of mitochondria in determining the fate of cells (life or death) has been well established (5, 14, 24, 29, 36, 44, 46), our study is the first to demonstrate that dysfunction of mitochondria is not merely pivotal in committing cells to die but is also critical in maintaining progressive apoptos…”
BackgroundHypothermia After Cardiac Arrest
Janata, A., & Holzer, M. S. (2009) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2009.07.001 · Cited by 73 · see citing works
Watkin, R., Nawrot, T. S., Potts, R. J., & Hart, B. A. (2002) · Toxicology · doi:10.1016/s0300-483x(02)00577-2 · Cited by 71 · see citing works
Mechanisms of load dependency of myocardial ischemia reperfusion injury.
Mozaffari, M. S., Liu, J. Y., Abebe, W., & Baban, B. (2013) · Europe PMC (PubMed Central) · Cited by 76 · see citing works
Gyulkhandanyan, A. V., Feeney, C. J., & Pennefather, P. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.02029.x · Cited by 65 · see citing works
Olaquindox-induced genotoxicity and oxidative DNA damage in human hepatoma G2 (HepG2) cells
Zou, J., Chen, Q., Tang, S., Jin, X., Chen, K., Zhang, T., & Xiao, X. (2009) · Mutation Research/Genetic Toxicology and Environmental Mutagenesis · doi:10.1016/j.mrgentox.2009.03.001 · Cited by 65 · see citing works
Oxidant injury occurs rapidly after cardiac arrest, cardiopulmonary resuscitation, and reperfusion*
Idris, A. H., Roberts, L. J., Caruso, L. J., et al. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000174104.50799.bd · Cited by 65 · see citing works
“Investigations conducted in cellular models showed that reperfusion of ischemic tissue is associated with a burst of reactive oxidant species within minutes after reperfusion (3, 4).”
BackgroundSelf-citationInterplay between Structure and Fluidity of Model Lipid Membranes under Oxidative Attack
Tai, W.-Y., Yang, Y., Lin, H.-J., Huang, C.-P., Cheng, Y., Chen, M.-F., Yen, H.-L., & Liau, I. (2010) · The Journal of Physical Chemistry B · doi:10.1021/jp1014719 · Cited by 64 · see citing works
Mitochondrial impairment is accompanied by impaired oxidative DNA repair in the nucleus
Delsite, R. (2003) · Mutagenesis · doi:10.1093/mutage/geg027 · Cited by 63 · see citing works
Sgobbo, P., Pacelli, C., Grattagliano, I., Villani, G., & Cocco, T. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.01.023 · Cited by 63 · see citing works
Shao, Z., Wojcik, K. R., Dossumbekova, A., Hsu, C., Mehendale, S. R., Li, C., Qin, Y., Sharp, W. W., Chang, W., Hamann, K. J., et al. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22170 · Cited by 58 · see citing works
Self-citationWatts, J. A., & Kline, J. A. (2003) · Academic Emergency Medicine · doi:10.1197/s1069-6563(03)00319-1 · Cited by 63 · see citing works
Wang, Z.-H., Chen, Y.-X., Zhang, C., Wu, L., Yu, Z., Cai, X., Guan, Y., Zhou, Z.-N., & Yang, H. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00276.2011 · Cited by 58 · see citing works
Nitrite as a mediator of ischemic preconditioning and cytoprotection
Murillo, D., Kamga, C., Mo, L., & Shiva, S. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.01.003 · Cited by 57 · see citing works
“While binding of NO to complex IV has been demonstrated to increase ROS generation due to electron accumulation at complexes I-III in the electron transport chain [117], this small increase in ROS generation may not play a large role in the progression of injury during ischemia.”
BackgroundInfluentialVerschoor, M. L., Wilson, A., & Singh, G. (2010) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y09-135 · Cited by 57 · see citing works
Jagadeeswaran, R., Jagadeeswaran, S., Bindokas, V. P., et al. (2007) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00147.2006 · Cited by 56 · see citing works
“ROS was measured by measuring changes in fluorescence resulting from intracellular probe oxidation as described previously (31, 32).”
MethodХалиулин, И. Г., Schwalb, H., Wang, P., Houminer, E., Grinberg, L. N., Katzeff, H. L., Borman, J. B., & Powell, S. R. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.04.017 · Cited by 55 · see citing works
Wang, Z.-H., Jl, L., Wu, L. M., Zhang, Y., & Yang, H.-T. (2014) · Cell Death and Disease · doi:10.1038/cddis.2014.267 · Cited by 55 · see citing works
The effects of ginsenoside Rb1 on JNK in oxidative injury in cardiomyocytes
Li, J., Shao, Z. H., Xie, J.-T., Wang, C. Z., Ramachandran, S., Yin, J., Aung, H. H., Li, C., Qin, G., Hoek, T. L. V., et al. (2012) · Archives of Pharmacal Research · doi:10.1007/s12272-012-0717-3 · Cited by 54 · see citing works
“This dye exhibited no toxicity in control cells even after a ten-hour exposure (Vanden Hoek et al., 1997).”
Self-citationŠepac, A., Sedlić, F., Si‐Tayeb, K., Lough, J., Duncan, S. A., Bienengraeber, M., Park, F., Kim, J., & Bosnjak, Z. J. (2010) · Anesthesiology · doi:10.1097/aln.0b013e3181eff6b7 · Cited by 48 · see citing works
“The cells stained with red-fluorescent propidium iodide (2 M; Sigma–Aldrich) were considered dead.(20) hESC-derived cardiomyocytes were preconditioned with 0.”
MethodAltered gene expression during hypoxia and reoxygenation of the heart
Piacentini, L., & Karliner, J. S. (1999) · Pharmacology & Therapeutics · doi:10.1016/s0163-7258(99)00010-8 · Cited by 47 · see citing works
Qin, Y., Hoek, T. L. V., Wojcik, K., et al. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01063.2003 · Cited by 47 · see citing works
“Cell contractions were assessed by observation of movement within the same field of cells as previously reported (39).”
MethodSelf-citationGrape Seed Proanthocyanidins Induce Pro-Oxidant Toxicity in Cardiomyocytes
Shao, Z., Hoek, T. L. V., Xie, J., et al. (2003) · Cardiovascular Toxicology · doi:10.1385/ct:3:4:331 · Cited by 44 · see citing works
“The contractions were assessed as previously reported (17).”
MethodSelf-citationYing, W., Anderson, C. M., Chen, Y., Stein-Behrens, B., Fahlman, C. S., Copin, J., Chan, P. H., & Swanson, R. A. (2000) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-200002000-00018 · Cited by 43 · see citing works
Chen, Y., Liu, J., Zheng, Y., Wang, J., Wang, Z., Gu, S., Tan, J., Jing, Q., & Yang, H. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu256 · Cited by 42 · see citing works
“Mitochondrial ATP and ROS production are regulated by a family of uncoupling proteins (UCPs), which are located in the mitochondrial inner membrane and catalyze a regulated proton leak from the intermembrane space into the mitochondrial matrix.20,21 There are three UCP family members, UCP1, 2, and 3.20 Their expressio…”
BackgroundInfluentialActivation of poly(ADP-ribose) polymerase in severe hemorrhagic shock and resuscitation
Watts, J. A., Grattan, R. M., Whitlow, B. S., & Kline, J. A. (2001) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.2001.281.2.g498 · Cited by 39 · see citing works
“Becker and colleagues (1, 41, 42) have recently examined electron leak from the electron transport system during anoxia in cardiomyocytes.”
BackgroundHeterogeneity of local myocardial flow and oxidative metabolism
Schwanke, U., Deußen, A., Heusch, G., et al. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.279.3.h1029 · Cited by 39 · see citing works
“Under physiological, normoxic conditions as used in this study, the myocardium incorporates about 98% of its oxygen uptake into oxidation water, whereas oxidant generation is negligible and amounts to only 1–2% (7, 34).”
MethodThe Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection
Smith, C. O., Nehrke, K. W., & Brookes, P. S. (2017) · Biochemical Journal · doi:10.1042/bcj20160623 · Cited by 37 · see citing works
Protective effect of edaravone against hypoxia–reoxygenation injury in rabbit cardiomyocytes
Yamawaki, M., Sasaki, N., Shimoyama, M., et al. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705775 · Cited by 37 · see citing works
“These findings suggest that the cardioprotective effects of edaravone are possibly due to protection of the mitochondria, the main source of energy production and ROS generation (Vanden Hoek et al., 1997; 2000; Sorescu & Griendling, 2002).”
BackgroundKing, N. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00182-2 · Cited by 37 · see citing works
Chang, W., Li, J., Hoek, M. S. V., Zhu, X., Li, C., Huang, H., Hsu, C.-W., Zhong, Q., Li, J., Chen, S., et al. (2013) · The American Journal of Chinese Medicine · doi:10.1142/s0192415x13500237 · Cited by 36 · see citing works
Self-citationAngelin, A., Bonaldo, P., & Bernardi, P. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.03.026 · Cited by 36 · see citing works
Dadakhujaev, S., NOH, H., JUNG, E., Hah, Y., Kim, C. D., & Kim, D.-H. (2008) · Experimental Cell Research · doi:10.1016/j.yexcr.2008.08.013 · Cited by 34 · see citing works
Mitochondrial membrane potentials in ischemic hearts
Berkich, D. A., Salama, G., & LaNoue, K. F. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.09.021 · Cited by 34 · see citing works
Ilan, E., Tirosh, O., & Madar, Z. (2005) · Journal of Nutrition · doi:10.1093/jn/135.9.2090 · Cited by 33 · see citing works
“Hepatocytes were stained with 2 mg/L DNA-interchelating dye propidium iodide, which is excluded by viable cells; with 1 mg/L Nile red, which accumulates in intracellular lipid droplets; or with 50 mmol/L dichlorodihydrofluorescein diacetate (H2DCF-DA), a probe that has high reactivity to hydrogen peroxide, lipid hydro…”
BackgroundMethodHindle, A. G., Lawler, J. M., Campbell, K. L., & Horning, M. (2009) · Journal of Experimental Zoology Part A Ecological Genetics and Physiology · doi:10.1002/jez.534 · Cited by 35 · see citing works
Aharoni-Simon, M., Reifen, R. M., & Tirosh, O. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1339 · Cited by 31 · see citing works
Janata, A., Bayegan, K., Weihs, W., et al. (2007) · Critical Care Medicine · doi:10.1097/01.ccm.0000288103.86029.66 · Cited by 31 · see citing works
Mitochondrial function: the heart of myocardial preservation
McFalls, E. O., Liem, D. A., Schoonderwoerd, K. C., Lamers, J. M. J., Sluiter, W. J., & Duncker, D. J. (2003) · Journal of Laboratory and Clinical Medicine · doi:10.1016/s0022-2143(03)00109-4 · Cited by 30 · see citing works
Dutkowski, P., Krug, A., Krysiak, M., et al. (2003) · Cryobiology · doi:10.1016/j.cryobiol.2003.08.004 · Cited by 29 · see citing works
Janata, A., Weihs, W., Schratter, A., et al. (2010) · Critical Care Medicine · doi:10.1097/ccm.0b013e3181e78b9a · Cited by 29 · see citing works
“Neurologic outcome for (median and interquartile range) the control group included overall performance category score of 3, neurologic deficit score of 45%; for the emergency preservation and resuscitation group, overall performance category score was 3 (2–5) and neurologic deficit score was 45% (36; 50) and in the em…”
BackgroundLai, B., Zhang, L., Dong, L.-Y., Zhu, Y., Sun, F., & Zheng, P. (2005) · Experimental Neurology · doi:10.1016/j.expneurol.2005.03.005 · Cited by 28 · see citing works
Mesenchymal stem cell-derived extracellular vesicles in the failing heart: past, present, and future
Karbasiafshar, C., Sellke, F. W., & Abid, M. R. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00951.2020 · Cited by 27 · see citing works
EDARAVONE REDUCES MYOCARDIAL INFARCT SIZE AND IMPROVES CARDIAC FUNCTION AND REMODELLING IN RABBITS
Onogi, H., Minatoguchi, S., Chen, X., Bao, N., Kobayashi, H., Misao, Y., Yasuda, S., Yamaki, T., Maruyama, R., Uno, Y., et al. (2006) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/j.1440-1681.2006.04483.x · Cited by 27 · see citing works
Childs, E. W., Tharakan, B., Hunter, F. A., Isong, M., & Liggins, N. D. (2008) · Shock · doi:10.1097/shk.0b013e318157f524 · Cited by 25 · see citing works
“During ischemia, indexes of oxidant stress were attenuated by mitochondrial electron transport inhibitors, suggesting that ROS are generated by mitochondrial complexes (24, 25).”
BackgroundThe Effect of Alpha-Lipoic Acid on Mitochondrial Superoxide and Glucocorticoid-Induced Hypertension
Ong, S. L. H., Vohra, H., Zhang, Y., Sutton, M., & Whitworth, J. A. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/517045 · Cited by 26 · see citing works
Jansen, S., Cashman, K. S., Thompson, J. G., Pantaleon, M., & Kaye, P. L. (2009) · Reproduction · doi:10.1530/rep-09-0038 · Cited by 26 · see citing works
Manganese superoxide dismutase inactivation during Fas (CD95)-mediated apoptosis in Jurkat T cells
Pardo, M., Melendez, J. A., & Tirosh, O. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.08.027 · Cited by 25 · see citing works
Apomorphine prevents myocardial ischemia/reperfusion-induced oxidative stress in the rat heart
Халиулин, И. Г., Schneider, A., Houminer, E., Borman, J. B., & Schwalb, H. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.06.029 · Cited by 25 · see citing works
Tenore, G. C., Manfra, M., Stiuso, P., Coppola, L., Russo, M., Monterrey, I. M. G., & Campiglia, P. (2012) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf301647d · Cited by 24 · see citing works
- Authors
- Vanden Hoek, T. L., Shao, Z., Li, C., Schumacker, P. T., & Becker, L. B.
- Affiliations
- University of Chicago (US)
- Venue
- Journal of Molecular and Cellular Cardiology
- Publisher
- Elsevier BV
- Published
- 1997-09
- Volume
- 29
- Issue
- 9
- Pages
- 2441-2450
- ISSN
- 0022-2828 (ISSN-L)
- OpenAlex
- W1560838288
- Cited by
- 161
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 3 · 2016: 1 · 2015: 1 · 2014: 9 · 2013: 10 · 2012: 6
- FWCI
- 2.67
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Molecular and Cellular Cardiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08hl003459-03)
- National Heart, Lung, and Blood Institute (HL 32646, HL-03459, R01HL035440, HL35440)
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- mitochondrial electron transport chain, oxidant injury, cardiomyocytes, ischemia-reperfusion injury, cyanide, antimycin, rotenone, oxygen concentration, hydroxyl radicals, hydrogen peroxide, 2-mercaptopropionylglycine, 1,10-phenanthroline, antioxidants, cell viability, cardiomyocyte contraction, hypoxia
- MeSH terms
- Animals, Antioxidants, Biological Transport, Cell Survival, Cells, Cultured, Chick Embryo, Cyanides, Electrons, Fluoresceins, Tiopronin, Mitochondria, Heart, Myocardial Contraction, Myocardium, Oxygen, Phenanthrolines, Oxidants, Cell Death, Oxidative Stress
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
