Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity

Facundo, Heberty T.F.; Carreira, Raquel S.; de Paula, Juliana G.; Santos, Célio C.X.; Ferranti, Renato; Laurindo, Francisco R.M.; Kowaltowski, Alicia J.

doi:10.1016/j.freeradbiomed.2005.08.041

Cited by 72Cardiac Ischemia and ReperfusionMitochondrial Function and PathologyCell death mechanisms and regulation

Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity

Facundo, Heberty T.F., Carreira, Raquel S., de Paula, Juliana G., Santos, Célio C.X., Ferranti, Renato, Laurindo, Francisco R.M., Kowaltowski, Alicia J.·2006·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2005.08.041

Open this paper in CoChat — free account

Abstract

Mitochondrial ATP-sensitive K+ channels (mitoKATP) mediate ischemic preconditioning, a cardioprotective procedure. MitoKATP activity has been proposed to either enhance or prevent the release of reactive oxygen species. This study tested the redox effects of mitoKATP in order to clarify the role of these channels during preconditioning. We found no evidence that mitoKATP channels increase mitochondrial reactive oxygen species release directly. In addition, neither ischemic preconditioning nor the mitoKATP agonist diazoxide increased antioxidant defenses. Furthermore, increases in reactive oxygen species observed during ischemic preconditioning were not inhibited by mitoKATP antagonists, suggesting that they occur upstream of channel activity. Antioxidants were tested to verify if diazoxide-promoted ischemic protection was dependent on reactive oxygen species. N-Acetylcysteine proved to be an inadequate antioxidant for these tests since it directly interfered with the ability of diazoxide to activate mitoKATP. Catalase reversed the beneficial effect of preconditioning, but not of diazoxide, indicating that reactive oxygen species mediating preconditioning occur upstream of mitoKATP. Taken together, these results demonstrate that ischemic preconditioning increases reactive oxygen release independently of mitoKATP and suggest that the activity of this channel prevents oxidative reperfusion damage by decreasing reactive oxygen species production.

Integrity signals

Registry

Crossref · 10.1016/j.freeradbiomed.2005.08.041

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

This might explain why a ROS-increasing effect of diazoxide has not been detected with NADH-generating substrates or without complex III inhibition.
“This might explain why a ROS-increasing effect of diazoxide has not been detected in the presence of NADH-generating substrates or when complex III was not inhibited [129,138,139].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [139]
Some lipid peroxidation products, such as HNE, may induce partial uncoupling of mitochondria through UCPs and are thought to initiate protective mechanisms.
“Some lipid peroxidation products, such as 4-hydroxy-trans-2-noneal (HNE) may induce partial uncoupling of mitochondria through UCPs and are thought to initiate protective mechanisms (41, 116).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [116]

Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium.
Murry, C. E., Jennings, R. B., & Reimer, K. A. (1986) · Circulation · doi:10.1161/01.cir.74.5.1124 · Cited by 7,813 · see citing works
Mitochondrial formation of reactive oxygen species
Turrens, J. F. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.049478 · Cited by 5,084 · see citing works
Evaluation of the probe 2',7'-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress
LeBel, C. P., Ischiropoulos, H., & Bondy, S. C. (1992) · Chemical Research in Toxicology · doi:10.1021/tx00026a012 · Cited by 2,694 · see citing works
Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation.
Bass, D., Parce, J. W., DeChatelet, L. R., Szejda, P., Seeds, M. C., & Thomas, M. (1983) · The Journal of Immunology · doi:10.4049/jimmunol.130.4.1910 · Cited by 1,811 · see citing works
HL-1 cells: a cardiac muscle cell line that contracts and retains phenotypic characteristics of the adult cardiomyocyte
Claycomb, W. C., Lanson, N. A., Stallworth, B. S., Egeland, D. B., Delcarpio, J. B., Bahinski, A., & Izzo, N. J. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.6.2979 · Cited by 1,546 · see citing works
Contribution of trends in survival and coronar y-event rates to changes in coronary heart disease mortality: 10-year results from 37 WHO MONICA Project populations
Tunstall-Pedoe, H., Kuulasmaa, K., Mähönen, M., Tolonen, H., & Ruokokoski, E. (1999) · The Lancet · doi:10.1016/s0140-6736(99)04021-0 · Cited by 1,444 · see citing works
Cardioprotective Effect of Diazoxide and Its Interaction With Mitochondrial ATP-Sensitive K+Channels
Garlid, K., Pauček, P., Yarov-Yarovoy, V. M., Murray, H. N., Darbenzio, R. B., DʼAlonzo, A. J., Lodge, N. J., Smith, M. A., & Grover, G. J. (1997) · Circulation Research · doi:10.1161/01.res.81.6.1072 · Cited by 1,019 · see citing works
Blockade of ATP-sensitive potassium channels prevents myocardial preconditioning in dogs.
Gross, G. J., & Auchampach, J. A. (1992) · Circulation Research · doi:10.1161/01.res.70.2.223 · Cited by 953 · see citing works
Mitochondrial damage induced by conditions of oxidative stress
Kowaltowski, A. J., & Vercesi, A. E. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(98)00216-0 · Cited by 866 · see citing works
Self-citation
Reactive oxygen species released from mitochondria during brief hypoxia induce preconditioning in cardiomyocytes
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
Opening of Mitochondrial K ATP Channels Triggers the Preconditioned State by Generating Free Radicals
Pain, T., Yang, X.-M., Critz, S. D., Yue, Y., Nakano, A., Liu, G. S., Heusch, G., Cohen, M. V., & Downey, J. M. (2000) · Circulation Research · doi:10.1161/01.res.87.6.460 · Cited by 662 · see citing works
Analysis of mitochondrial morphology and function with novel fixable fluorescent stains.
Poot, M., Zhang, Y. Z., Kramer, J., Wells, K. S., Jones, L. J., Hanzel, D. K., Lugade, A. G., Singer, V. L., & Haugland, R. P. (1996) · Journal of Histochemistry & Cytochemistry · doi:10.1177/44.12.8985128 · Cited by 521 · see citing works
Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma
Mattiasson, G., Shamloo, M., Gido, G., Mathi, K., Tomasevic, G., Yi, S., Warden, C. H., Castilho, R. F., Melcher, T., Gonzalez-Zulueta, M., et al. (2003) · Nature Medicine · doi:10.1038/nm903 · Cited by 515 · see citing works
Mitochondrial H + Leak and ROS Generation: An Odd Couple
Brookes, P. S. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.10.016 · Cited by 447 · see citing works
Evidence for Mitochondrial K + Channels and Their Role in Cardioprotection
O'Rourke, B. P. (2004) · Circulation Research · doi:10.1161/01.res.0000117583.66950.43 · Cited by 444 · see citing works
Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism
Forbes, R. A., Steenbergen, C., & Murphy, E. (2001) · Circulation Research · doi:10.1161/hh0801.089342 · Cited by 395 · see citing works
Bioenergetic consequences of opening the ATP-sensitive K+channel of heart mitochondria
Kowaltowski, A. J., Seetharaman, S., Pauček, P., & Garlid, K. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.2.h649 · Cited by 351 · see citing works
Self-citation
Mitochondrial potassium transport: the role of the mitochondrial ATP-sensitive K+ channel in cardiac function and cardioprotection
Garlid, K., Santos, P. D. D., Xie, Z., Costa, A. D. T., & Pauček, P. (2003) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/s0005-2728(03)00109-9 · Cited by 332 · see citing works
KATP channels and myocardial preconditioning: an update
Gross, G. J., & Peart, J. N. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00421.2003 · Cited by 324 · see citing works
Preconditioning 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
Blockade of ischaemic preconditioning in dogs by the novel ATP dependent potassium channel antagonist sodium 5-hydroxydecanoate
Auchampach, J. A., Grover, G. J., & Gross, G. J. (1992) · Cardiovascular Research · doi:10.1093/cvr/26.11.1054 · Cited by 278 · see citing works
Selective Pharmacological Agents Implicate Mitochondrial but Not Sarcolemmal KATPChannels in Ischemic Cardioprotection
Sato, T., Sasaki, N., Seharaseyon, J., O'Rourke, B. P., & Marbán, E. (2000) · Circulation · doi:10.1161/01.cir.101.20.2418 · Cited by 267 · see citing works
State-dependent Inhibition of the Mitochondrial KATP Channel by Glyburide and 5-Hydroxydecanoate
Jabůrek, M., Yarov-Yarovoy, V. M., Pauček, P., & Garlid, K. (1998) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)57796-1 · Cited by 254 · see citing works
ROS and NO trigger early preconditioning: relationship to mitochondrial KATP channel
Lebuffe, G., Schumacker, P. T., Shao, Z.-H., Anderson, T., Iwase, H., & Vanden Hoek, T. L. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00706.2002 · Cited by 227 · see citing works
Ischemic preconditioning in rats: role of mitochondrial KATPchannel in preservation of mitochondrial function
Fryer, R. M., Eells, J. T., Hsu, A. K., Henry, M. M., & Gross, G. J. (2000) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2000.278.1.h305 · Cited by 223 · see citing works
Phenoxyl Free Radical Formation during the Oxidation of the Fluorescent Dye 2′,7′-Dichlorofluorescein by Horseradish Peroxidase
Rota, C., Fann, Y. C., & Mason, R. P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.40.28161 · Cited by 221 · see citing works
Characteristics and Superoxide-Induced Activation of Reconstituted Myocardial Mitochondrial ATP-Sensitive Potassium Channels
Zhang, D. X., Chen, Y., Campbell, W. B., Zou, A.-P., Gross, G. J., & Li, P. (2001) · Circulation Research · doi:10.1161/hh2401.101752 · Cited by 203 · see citing works
Mitochondrial KATP channels: role in cardioprotection
Oldenburg, O. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00439-x · Cited by 202 · see citing works
Activation of Mitochondrial ATP-Sensitive K + Channel for Cardiac Protection Against Ischemic Injury Is Dependent on Protein Kinase C Activity
Wang, Y., Hirai, K., & Ashraf, M. (1999) · Circulation Research · doi:10.1161/01.res.85.8.731 · Cited by 198 · see citing works
Potassium channel openers protect cardiac mitochondria by attenuating oxidant stress at reoxygenation
Özcan, 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
Mitochondrial superoxide and aging: uncoupling-protein activity and superoxide production
Brand, M. D., Buckingham, J. A., Esteves, T. C., Green, K., Lambert, A. J., Miwa, S., Murphy, M. P., Pakay, J. L., Talbot, D. A., & Echtay, K. S. (2004) · Biochemical Society Symposia · doi:10.1042/bss0710203 · Cited by 182 · see citing works
Mitochondrial Uncoupling Protein 1 Expressed in the Heart of Transgenic Mice Protects Against Ischemic-Reperfusion Damage
Hoerter, J. A., González‐Barroso, M. M., Couplan, E., Matéo, P., Gelly, C., Cassard, A., Diolez, P., & Bouillaud, F. (2004) · Circulation · doi:10.1161/01.cir.0000137824.30476.0e · Cited by 149 · see citing works
Opening of ATP-sensitive potassium channels causes generation of free radicals in vascular smooth muscle cells
Krenz, M., Oldenburg, O., Wimpee, H., Cohen, M. V., Garlid, K., Critz, S. D., Downey, J. M., & Benoit, J. N. (2002) · Basic Research in Cardiology · doi:10.1007/s003950200045 · Cited by 145 · see citing works
Mitochondrial ATP‐sensitive K+ channel opening decreases reactive oxygen species generation
Ferranti, R., da Silva, M. M., & Kowaltowski, A. J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00007-3 · Cited by 136 · see citing works
Self-citation
Mitochondrial KATP channel opening protects a human atrial-derived cell line by a mechanism involving free radical generation
Carroll, R. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00330-3 · Cited by 122 · see citing works
“Mild” Uncoupling of Mitochondria
Starkov, A. A. (1997) · Bioscience Reports · doi:10.1023/a:1027380527769 · Cited by 119 · see citing works
Chloromethyltetramethylrosamine (Mitotracker OrangeTM) Induces the Mitochondrial Permeability Transition and Inhibits Respiratory Complex I
Scorrano, L., Petronilli, V., Colonna, R., Lisa, F. D., & Bernardi, P. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.35.24657 · Cited by 115 · see citing works
Mitochondrial ATP-Sensitive K+ Channels Prevent Oxidative Stress, Permeability Transition and Cell Death
Facundo, H. T., de Paula, J. G., & Kowaltowski, A. J. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-4130-1 · Cited by 93 · see citing works
Self-citation
Determination of intracellular glutathione and thiols by high performance liquid chromatography with a gold electrode at the femtomole level: comparison with a spectroscopic assay
Hiraku, Y., Murata, M., & Kawanishi, S. (2002) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/s0304-4165(02)00152-6 · Cited by 90 · see citing works
Ischemic preconditioning inhibits mitochondrial respiration, increases H2O2release, and enhances K+transport
da Silva, M. M., Sartori, A., Belisle, E., & Kowaltowski, A. J. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00955.2002 · Cited by 73 · see citing works
Self-citation
H2O2opens mitochondrial KATPchannels and inhibits GABA receptors via protein kinase C-ε in cardiomyocytes
Zhang, H., McPherson, B. C., Liu, H., Baman, T. S., Rock, P., & Yao, Z. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00683.2001 · Cited by 66 · see citing works
H2O2 generation in Saccharomyces cerevisiae respiratory pet mutants: effect of cytochrome c
de Barros, M. H. (2003) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(03)00307-1 · Cited by 65 · see citing works
P1075 opens mitochondrial KATP channels and generates reactive oxygen species resulting in cardioprotection of rabbit hearts
Oldenburg, O. (2003) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(03)00151-2 · Cited by 54 · see citing works
Opening of Mitochondrial K+ Channels Increases Ischemic ATP Levels by Preventing Hydrolysis
Belisle, E., & Kowaltowski, A. J. (2002) · Journal of Bioenergetics and Biomembranes · doi:10.1023/a:1020256502583 · Cited by 40 · see citing works
Self-citation
Modification of the Mitochondrial Sulfonylurea Receptor by Thiol Reagents
Szewczyk, A. M., Wójcik, G., Lobanov, N. A., & Nałȩcz, M. J. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.1190 · Cited by 24 · see citing works
HL-1 myocytes exhibit PKC and K ATP channel-dependent delta opioid preconditioning 1,2 1This was presented at the annual meeting of the Association for Academic Surgery, Boston, MA, November 7–9, 2002. 2The present study was supported by a grant from the National Institutes of Health-NHLBI, HL58781.
Seymour, E. M., Wu, S.-Y. J., Kovach, M. A., Romano, M. A., Traynor, J. R., Claycomb, W. C., & Bolling, S. F. (2003) · Journal of Surgical Research · doi:10.1016/s0022-4804(03)00248-8 · Cited by 22 · see citing works
Both Metabolic Inhibition and Mitochondrial K ATP Channel Opening Are Myoprotective and Initiate a Compensatory Sarcolemmal Outward Membrane Current
Irie, H., Gao, J., Gaudette, G. R., Cohen, I. S., Mathias, R. T., Saltman, A. E., & Krukenkamp, I. B. (2003) · Circulation · doi:10.1161/01.cir.0000087431.91602.e2 · Cited by 14 · see citing works
Fluorometric estimation of dead cells in cell suspensions
Karsten, U. R. (1980) · Cellular and Molecular Life Sciences · doi:10.1007/bf01953772 · Cited by 9 · see citing works
No evidence of mitokATP channel-mediated elevation of reactive oxygen species in isolated rabbit ventricular myocytes
Cone, J. L., & Liu, Y. (2001) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(01)90090-2 · Cited by 4 · see citing works

Flagged first, then by citations

Sorted by citations

Mitochondria and reactive oxygen species
Kowaltowski, A. J., de Souza-Pinto, N. C., Castilho, R. F., & Vercesi, A. E. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.004 · Cited by 1,162 · see citing works
Self-citation
Tissue-, substrate-, and site-specific characteristics of mitochondrial reactive oxygen species generation
Tahara, E. B., Navarete, F. D. T., & Kowaltowski, A. J. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.02.008 · Cited by 479 · see citing works
Self-citation
Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function
Stowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471 · see citing works
Why does Brain Metabolism not Favor Burning of Fatty Acids to Provide Energy? - Reflections on Disadvantages of the Use of Free Fatty Acids as Fuel for Brain
Schönfeld, P., & Reiser, G. (2013) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2013.128 · Cited by 457 · see citing works
Crosstalk signaling between mitochondrial Ca2+ and ROS
Robert, F. F. (2009) · Frontiers in bioscience · doi:10.2741/3303 · Cited by 439 · see citing works
The role of mitochondria in protection of the heart by preconditioning
Halestrap, A. P., Clarke, S. J., & Khaliulin, I. (2007) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2007.05.008 · Cited by 390 · see citing works
Mitochondrial Channels: Ion Fluxes and More
Szabó, I., & Zoratti, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00021.2013 · Cited by 321 · see citing works
Reactive oxygen species and nitric oxide in plant mitochondria: origin and redundant regulatory systems
Blokhina, O. B., & Fagerstedt, K. (2009) · Physiologia Plantarum · doi:10.1111/j.1399-3054.2009.01340.x · Cited by 235 · see citing works
Acute oxidative stress and systemic Nrf2 activation by the ketogenic diet
Milder, J. B., Liang, L., & Patel, M. (2010) · Neurobiology of Disease · doi:10.1016/j.nbd.2010.05.030 · Cited by 214 · see citing works
Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning
Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.004 · Cited by 201 · see citing works
Mitochondria as a Target for the Cardioprotective Effects of Nitric Oxide in Ischemia–Reperfusion Injury
Burwell, L. S., & Brookes, P. S. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1845 · Cited by 172 · see citing works
Positive oxidative stress in aging and aging-related disease tolerance
Yan, L. (2014) · Redox Biology · doi:10.1016/j.redox.2014.01.002 · Cited by 170 · see citing works
Mitochondrial nitroalkene formation and mild uncoupling in ischaemic preconditioning. Implications for cardioprotection
Nadtochiy, S. M., Baker, P. R. S., Freeman, B. A., & Brookes, P. S. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvn323 · Cited by 131 · see citing works
Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production
Facundo, H. T., de Paula, J. G., & Kowaltowski, A. J. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.001 · Cited by 123 · see citing works
Self-citation
A review of myocardial ischaemia/reperfusion injury: Pathophysiology, experimental models, biomarkers, genetics and pharmacological treatment
Günata, M., & Parlakpınar, H. (2020) · Cell Biochemistry and Function · doi:10.1002/cbf.3587 · Cited by 118 · see citing works
Redox regulation of the mitochondrial KATP channel in cardioprotection
Queliconi, B. B., Wojtovich, A. P., Nadtochiy, S. M., Kowaltowski, A. J., & Brookes, P. S. (2010) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2010.11.005 · Cited by 99 · see citing works
Self-citation
Redox Control of Apoptosis: An Update
Filomeni, G., & Ciriolo, M. R. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.2187 · Cited by 92 · see citing works
Mitochondrial Ca2+ transport, permeability transition and oxidative stress in cell death: implications in cardiotoxicity, neurodegeneration and dyslipidemias
Vercesi, A. E. (2006) · Frontiers in bioscience · doi:10.2741/1990 · Cited by 81 · see citing works
Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III
Dröse, S., Hanley, P. J., & Brandt, U. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.01.011 · Cited by 72 · see citing works
Mitochondria and Cardiac Hypertrophy.
Facundo, H. D. T. F., Brainard, R. E., Caldas, F. R. D. L., & Lucas, A. M. B. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/978-3-319-55330-6_11 · Cited by 70 · see citing works
Self-citation
Preconditioning by an in situ administration of hydrogen peroxide: Involvement of reactive oxygen species and mitochondrial ATP-dependent potassium channel in a cerebral ischemia–reperfusion model
Simerabet, M., Robin, E., Aristi, I., Adamczyk, S., Tavernier, B., Vallet, B., Bordet, R., & Lebuffe, G. (2008) · Brain Research · doi:10.1016/j.brainres.2008.08.070 · Cited by 57 · see citing works
Redox signaling triggers protection during the reperfusion rather than the ischemic phase of preconditioning
Dost, T., Cohen, M. V., & Downey, J. M. (2008) · Basic Research in Cardiology · doi:10.1007/s00395-008-0718-z · Cited by 57 · see citing works
Concentration-dependent wrestling between detrimental and protective effects of H2O2 during myocardial ischemia/reperfusion
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
Mitochondrial ion transport pathways: Role in metabolic diseases
Cardoso, A. R., Queliconi, B. B., & Kowaltowski, A. J. (2010) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2009.12.017 · Cited by 54 · see citing works
Self-citation
Redox properties of the adenoside triphosphate‐sensitive K+ channel in brain mitochondria
Fornazari, M., de Paula, J. G., Castilho, R. F., & Kowaltowski, A. J. (2008) · Journal of Neuroscience Research · doi:10.1002/jnr.21614 · Cited by 53 · see citing works
Self-citation
ROS-Independent Preconditioning in Neurons via Activation of mitoK ATP Channels by BMS-191095
Gáspár, T., Snipes, J. A., Busija, A. R., Kis, B., Domoki, F., Bari, F., & Busija, D. W. (2008) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/sj.jcbfm.9600611 · Cited by 51 · see citing works
Mitochondrial Therapeutics for Cardioprotection
Carreira, R., Lee, P. P. W., & Gottlieb, R. A. (2011) · Current Pharmaceutical Design · doi:10.2174/138161211796904777 · Cited by 47 · see citing works
Self-citation
Brief femoral artery ischaemia provides protection against myocardial ischaemia–reperfusion injury in rats: the possible mechanisms
Shahid, M., Tauseef, M., Sharma, K. K., & Fahim, M. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2007.041442 · Cited by 45 · see citing works
Mitochondrial targets for volatile anesthetics against cardiac ischemia-reperfusion injury
Agarwal, B., Stowe, D. F., Dash, R. K., Bosnjak, Z. J., & Camara, A. K. S. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00341 · Cited by 43 · see citing works
Signaling pathways targeting mitochondrial potassium channels
Rotko, D., Kunz, W. S., Szewczyk, A. M., & Kulawiak, B. (2020) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2020.105792 · Cited by 39 · see citing works
Drug-induced mitochondrial dysfunction in cardiac and skeletal muscle injury
Sardão, V. A., Pereira, S. L., & Oliveira, P. J. (2008) · Expert Opinion on Drug Safety · doi:10.1517/14740338.7.2.129 · Cited by 33 · see citing works
Noninvasive Delayed Limb Ischemic Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by a Mitochondrial KATP Channel-Dependent Mechanism
Wu, Y., Yu, H., Zhu, X., YUAN, H.-J., Kang, Y., Jiao, J., GAO, W.-Z., Liu, Y., & Lou, J. (2011) · Physiological Research · doi:10.33549/physiolres.931944 · Cited by 32 · see citing works
The Mitochondrial ATP-Sensitive Potassium Channel Blocker 5-Hydroxydecanoate Inhibits Toxicity of 6-Hydroxydopamine on Dopaminergic Neurons
Rodríguez‐Pallares, J., Parga, J. A., Joglar, B., Guerra, M. J., & Labandeira-García, J. L. (2009) · Neurotoxicity Research · doi:10.1007/s12640-009-9010-8 · Cited by 31 · see citing works
Diazoxide protects against methylmalonate-induced neuronal toxicity
Kowaltowski, A. J., Maciel, E. N., Fornazari, M., & Castilho, R. F. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.04.004 · Cited by 28 · see citing works
Self-citation
Untargeted metabolomics reveals a mild impact of remote ischemic conditioning on the plasma metabolome and α-hydroxybutyrate as a possible cardioprotective factor and biomarker of tissue ischemia
Laursen, M. R., Hansen, J., Elkjær, C. C., Stavnager, N., Nielsen, C. B., Pryds, K., Johnsen, J., Nielsen, J. M., Bøtker, H. E., & Johannsen, M. (2017) · Metabolomics · doi:10.1007/s11306-017-1202-2 · Cited by 26 · see citing works
Bicarbonate Increases Ischemia-Reperfusion Damage by Inhibiting Mitophagy
Queliconi, B. B., Kowaltowski, A. J., & Gottlieb, R. A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0167678 · Cited by 26 · see citing works
Self-citation
Crocetin alleviates myocardial ischemia/reperfusion injury by regulating inflammation and the unfolded protein response
Yang, M., Mao, G., Ouyang, L., Shi, C., Hu, P., & Huang, S. (2019) · Molecular Medicine Reports · doi:10.3892/mmr.2019.10891 · Cited by 24 · see citing works
Beneficial effects of adenosine triphosphate-sensitive K+channel opener on liver ischemia/reperfusion injury
Nogueira, M. A. (2014) · World Journal of Gastroenterology · doi:10.3748/wjg.v20.i41.15319 · Cited by 22 · see citing works
Mitochondrial ATP-sensitive K+ channels mediate the antioxidative influence of diosgenin on myocardial reperfusion injury in rat hearts
Badalzadeh, R., Yavari, R., & Chalabiani, D. (2015) · General Physiology and Biophysics · doi:10.4149/gpb_2015009 · Cited by 22 · see citing works
Mitochondrial potassium channels: A novel calcitriol target
Olszewska, A., Sieradzan, A. K., Bednarczyk, P., Szewczyk, A. M., & Zmijewski, M. A. (2022) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-021-00299-0 · Cited by 21 · see citing works
Plant based steroidal and triterpenoid sapogenins: Chemistry on diosgenin and biological aspects
Pathak, N., & Negi, A. S. (2024) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2024.116915 · Cited by 20 · see citing works
Pathophysiologic role of ischemia reperfusion injury: A review
Vishwakarma, V. K., Upadhyay, P. K., Gupta, J. K., & Yadav, H. N. (2017) · Journal of Indian College of Cardiology · doi:10.1016/j.jicc.2017.06.017 · Cited by 20 · see citing works
Flavonoids as new regulators of mitochondrial potassium channels: contribution to cardioprotection
Kampa, R. P., Sęk, A., Bednarczyk, P., Szewczyk, A. M., Calderone, V., & Testai, L. (2022) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgac093 · Cited by 19 · see citing works
Bicarbonate modulates oxidative and functional damage in ischemia–reperfusion
Queliconi, B. B., Marazzi, T. B. M., Vaz, S. M., Brookes, P. S., Nehrke, K. W., Augusto, O., & Kowaltowski, A. J. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.11.007 · Cited by 18 · see citing works
Self-citation
Mitochondrial ATP-sensitive Potassium Channel Opening Inhibits Isoproterenol-induced Cardiac Hypertrophy by Preventing Oxidative Damage
Caldas, F. R. D. L., Leite, I. M. R., Filgueiras, A. B. T., Júnior, I. L. D. F., de Sousa, T. A. G. M., Martins, P. R., Kowaltowski, A. J., & Facundo, H. T. (2015) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000210 · Cited by 18 · see citing works
Self-citation
Pharmacological and molecular docking studies reveal that glibenclamide competitively inhibits diazoxide-induced mitochondrial ATP-sensitive potassium channel activation and pharmacological preconditioning
Palácio, P. B., Lucas, A. M. B., Alexandre, J. V. D. L., Cunha, P. L. O., Viana, Y. I. P., Albuquerque, A. C., Varela, A. L. N., & Facundo, H. T. (2021) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2021.174379 · Cited by 18 · see citing works
Self-citation
Hyperbaric oxygenation improves redox control and reduces mortality in the acute phase of myocardial infarction in a rat model
Oliveira, M., Tanaka, L. Y., Antônio, E. L., Brandizzi, L. I., Serra, A. J., dos SANTOS, L., Krieger, J. E., Laurindo, F. R. M., & Tucci, P. J. F. (2020) · Molecular Medicine Reports · doi:10.3892/mmr.2020.10968 · Cited by 16 · see citing works
Self-citation
Diazoxide affects mitochondrial bioenergetics by the opening of mKATP channel on submicromolar scale
Ov, A., Kolchinskaya, L. I., Nosar, V. I., Im, M., & Sagach, V. F. (2020) · BMC Molecular and Cell Biology · doi:10.1186/s12860-020-00275-0 · Cited by 15 · see citing works
Diazoxide preconditioning alleviates caspase-dependent and caspase-independent apoptosis induced by anoxia-reoxygenation of PC12 cells
Zhang, H., Zhao, D., Wang, Z., & Zheng, D. (2010) · The Journal of Biochemistry · doi:10.1093/jb/mvq074 · Cited by 14 · see citing works
A shortcut to mitochondrial signaling and pathology: A commentary on “Nonenzymatic formation of succinate in mitochondria under oxidative stress”
Brookes, P. S., Freeman, R. S., & Barone, M. C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.03.019 · Cited by 13 · see citing works
Mitochondrial Adaptive Responses to Hypertriglyceridemia and Bioactive Lipids
Alberici, L. C., & Oliveira, H. C. F. (2021) · Antioxidants and Redox Signaling · doi:10.1089/ars.2021.0180 · Cited by 12 · see citing works
Potent Cardioprotective Effect of the 4-Anilinoquinazoline Derivative PD153035: Involvement of Mitochondrial KATP Channel Activation
Cavalheiro, R. A., Marin, R. M., Rocco, S. A., Cerqueira, F. M., da Silva, C. C. C., Rittner, R., Kowaltowski, A. J., Vercesi, A. E., Franchini, K. G., & Castilho, R. F. (2010) · PLoS ONE · doi:10.1371/journal.pone.0010666 · Cited by 12 · see citing works
Self-citation
Ischemic preconditioning enhances fatty acid-dependent mitochondrial uncoupling
Carreira, R., Miyamoto, S., Mascio, P. D., Gonçalves, L. M. M., Monteiro, P. F., Providência, L. A., & Kowaltowski, A. J. (2007) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-007-9093-y · Cited by 12 · see citing works
Self-citation
Competitive interaction between ATP and GTP regulates mitochondrial ATP-sensitive potassium channels
Palácio, P. B., Soares, G. C. D. F., Lima, G. M. B., Cunha, P. L. O., Varela, A. L. N., & Facundo, H. T. (2023) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2023.110560 · Cited by 11 · see citing works
Self-citation
Genomic and non-genomic action of vitamin D on ion channels – Targeting mitochondria
Olszewska, A. M., & Zmijewski, M. A. (2024) · Mitochondrion · doi:10.1016/j.mito.2024.101891 · Cited by 10 · see citing works
Mechanism of Ischemia and Reperfusion Injury to the Heart: From the Viewpoint of Nitric Oxide and Mitochondria
Ha, S. J., & Kim, W. (2010) · Chonnam Medical Journal · doi:10.4068/cmj.2010.46.3.129 · Cited by 10 · see citing works
AIF-mediated mitochondrial pathway is critical for the protective effect of diazoxide against SH-SY5Y cell apoptosis
Zhang, H., Wang, Z., Zhao, D., Zheng, D., Feng, J., Li-chun, S., & Luo, Y. (2010) · Brain Research · doi:10.1016/j.brainres.2010.11.019 · Cited by 9 · see citing works
Technologies for tissue preservation: the role of endogenous and exogenous antioxidants in preserving tissue function in chinook salmon, Oncorhynchus tshawytscha
Tuckey, N. P. L. (2008) · UC Research Repository (University of Canterbury) · doi:10.26021/8417 · Cited by 3 · see citing works
Mitochondrial ATP-sensitive K + channels (MitoK ATP ) regulate brown adipocyte differentiation and metabolism
Pereira, O. R., Serna, J. D. C., da Silva, C. C. C., Camara, H., Kodani, S. D., Festuccia, W. T., Tseng, Y., & Kowaltowski, A. J. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00070.2025 · Cited by 2 · see citing works
Self-citation
Multicarrier Nanoplatforms for Precise Targeting of Cellular Energy Centers in Ischemic Heart Disease Therapy
Zhang, W., Xiao, H. J., Ma, Y., Lyu, X., Li, K., He, L., & Liu, S. (2025) · ACS Nano Medicine · doi:10.1021/acsnanomed.5c00057 · Cited by 2 · see citing works
Mitochondria and Ageing
Rodrigues, T. (2024) · Springer eBooks · doi:10.1007/978-3-031-55022-5_6 · Cited by 2 · see citing works
Cardioprotetic Effect of Diosgenin: Progress and Challenge
Neto, J. M. M., Amaral, R. G., Maia, M. I. A., dos Santos, S. A., Silva, E. A. P., Menezes, M. G. V., & Lauton‐Santos, S. (2019) · Saudi Journal of Biomedical Research · doi:10.36348/sjbr.2019.v04i10.001 · Cited by 1 · see citing works
Mitochondrial Reactive Oxygen Species in Myocardial Pre- and Postconditioning
Cardoso, A. R., Queliconi, B. B., & Kowaltowski, A. J. (2010) · Humana Press eBooks · doi:10.1007/978-1-60761-600-9_5 · Cited by 1 · see citing works
Self-citation
Efeitos redox e protetores do pré-condicionamento isquêmico e da abertura do canal mitocondrial de potássio sensível a ATP contra morte celular por isquemia e reperfusão cardíaca
Facundo, H. T. (2007) · doi:10.11606/t.46.2007.tde-27052008-091351 · Cited by 1 · see citing works
Self-citation
Efeito de dietas hiperlipídicas sobre mitocôndrias de fígado de camundongos: bioenergética, transporte de K+ e estudo redox
Cardoso, A. R. (2009) · doi:10.11606/d.46.2009.tde-10122009-105758
Influência da restrição calórica no metabolismo bioenergético e estado redox de Saccharomyces cerevisiae e Kluyveromyces lactis
Tahara, E. B. (2012) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.46.2012.tde-15052012-085726
Bicarbonato/CO2 aumenta dano em isquemia-reperfusão: da observação inicial à caracterização molecular
Queliconi, B. B. (2014) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.46.2014.tde-19012015-143431
Mecanismos de acción de intervenciones cardioprotectoras durante la isquemia y la reperfusión en ratas normales e hipertróficas
Fantinelli, J. C. (2009) · doi:10.35537/10915/4354
A glibenclamide analog lacking the cyclohexylurea portion fails to block ischemic preconditioning-induced mitochondrial and cardiac protection against ischemia/reperfusion injury
Palácio, P. B., Soares, G. C. D. F., & Facundo, H. T. (2025) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2025.110418
Self-citation
Mitochondrial Channels as Potential Targets for Pharmacological Strategies in Brain Ischemia
Milton, R. H., & Duchen, M. R. (2009) · Humana Press eBooks · doi:10.1007/978-1-60761-280-3_3
Additional file 1 of Diazoxide affects mitochondrial bioenergetics by the opening of mKATP channel on submicromolar scale
Ov, A., Kolchinskaya, L. I., Nosar, V. I., Mankovska, I., & Sagach, V. F. (2020) · Figshare · doi:10.6084/m9.figshare.12153822
Caloric Restriction Promotes Ischemia/Reperfusion Cardioprotection Through Increased Mitochondrial Na + /Ca 2+ ExchangePreprint
Queiroz, M., da Silva, C. C. C., Vogt, É. L., Cruz, M. A. E., Serna, J. D. C., Bechara, L. R. G., Ferreira, J. C. B., Facundo, H. T., & Kowaltowski, A. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.20.739602
Self-citation

Mitochondrial ATP-sensitive K+ channels are redox-sensitive pathways that control reactive oxygen species production
Facundo, H. T., de Paula, J. G., & Kowaltowski, A. J. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.001 · Cited by 123 · see citing works
Self-citation
Focused issue on KATP channels K ATP channels and preconditioning: A re-examination of the role of mitochondrial K ATP channels and an overview of alternative mechanisms
Hanley, P. J., & Daut, J. (2005) · Cited by 1 · see citing works
Ischemic preconditioning inhibits mitochondrial respiration, increases H2O2release, and enhances K+transport
da Silva, M. M., Sartori, A., Belisle, E., & Kowaltowski, A. J. (2003) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00955.2002 · Cited by 73 · see citing works
Self-citation
K channels and preconditioning: A re-examination of the role of mitochondrial K channels and an overview of alternative mechanisms
HANLEY, P., & DAUT, J. (2005) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2005.04.002 · Cited by 218 · see citing works
Mitochondrial ATP‐Dependent Potassium Channels: Viable Candidate Effectors of Ischemic Preconditioninga
Liu, Y., Sato, T., Seharaseyon, J., Szewczyk, A. M., O'Rourke, B. P., & Marbán, E. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb09222.x · Cited by 141 · see citing works

Authors: Facundo, H. T. F., Carreira, R. S., de Paula, J. G., Santos, C. C. X., Ferranti, R., Laurindo, F. R. M., & Kowaltowski, A. J.
Affiliations: Universidade de São Paulo (BR)
Corresponding author: Kowaltowski, Alicia J.
ORCID: Facundo, Heberty T.F.
Carreira, Raquel S.
Ferranti, Renato
Laurindo, Francisco R.M.
Kowaltowski, Alicia J.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2006-02
Volume: 40
Issue: 3
Pages: 469-479
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2005.08.041
OpenAlex: W2010935932
Cited by: 72
References: 49
Citations by year: 2025: 4 · 2024: 3 · 2023: 1 · 2022: 2 · 2021: 2 · 2020: 5 · 2019: 2 · 2017: 3 · 2016: 1 · 2015: 2 · 2014: 6 · 2013: 2 · 2012: 2
FWCI: 3.79
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: Fundação de Amparo à Pesquisa do Estado de São Paulo
Fundação para a Ciência e a Tecnologia
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 › Cell death mechanisms and regulation
Keywords: ischemic preconditioning, mitochondrial ATP-sensitive potassium channel, reactive oxygen species, diazoxide, cardioprotection, catalase, N-acetylcysteine, antioxidant defense, redox signaling
MeSH terms: Acetylcysteine, Adenosine Triphosphate, Animals, Antioxidants, Catalase, Diazoxide, Hydrogen Peroxide, Male, Mitochondria, Heart, Oxidation-Reduction, Potassium Channels, Rats, Sprague-Dawley, Reactive Oxygen Species, Ischemic Preconditioning, Rats

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

Ischemic preconditioning requires increases in reactive oxygen release independent of mitochondrial K+ channel activity

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks