Ischemic preconditioning inhibits mitochondrial respiration, increases H2O2release, and enhances K+transport
Abstract
Ischemic preconditioning, or the protective effect of short ischemic episodes on a longer, potentially injurious, ischemic period, is prevented by antagonists of mitochondrial ATP-sensitive K+channels (mitoK ATP) and involves changes in mitochondrial energy metabolism and reactive oxygen release after ischemia. However, the effects of ischemic preconditioning itself on mitochondria are still poorly understood. We determined the effects of ischemic preconditioning on isolated heart mitochondria and found that two brief (5 min) ischemic episodes are sufficient to induce a small but significant decrease (∼25%) in mitochondrial NADH-supported respiration. Preconditioning also increased mitochondrial H 2 O 2 release, an effect related to respiratory inhibition, because it is not observed in the presence of succinate plus rotenone and can be mimicked by chemically inhibiting complex I in the presence of NADH-linked substrates. In addition, preconditioned mitochondria presented more substantial ATP-sensitive K+transport, indicative of higher mitoK ATP activity. Thus we directly demonstrate that preconditioning leads to mitochondrial respiratory inhibition in the presence of NADH-linked substrates, increased reactive oxygen release, and activation of mitoK ATP.
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Stigmatellin blocks transfer of the first electron to the Fe-S center.
“Stigmatellin blocks transfer of the first electron to the Fe-S center (center P, QH2 oxidation site Qo) (96).”
From Mitochondrial reactive oxygen species production in excitable cells: Modulators of mitochondrial and cell function (2009) · cites this paper as [96]
Cites
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
Korshunov, S. S., Skulachev, V. P., & Starkov, A. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01159-9 · Cited by 1,727 · see citing works
Liu, G. S., Thornton, J. D., Winkle, D. M. V., Stanley, A., Olsson, R. A., & Downey, J. M. (1991) · Circulation · doi:10.1161/01.cir.84.1.350 · Cited by 1,351 · see citing works
Direct measurement of free radical generation following reperfusion of ischemic myocardium.
Zweier, J. L., Flaherty, J. T., & Weisfeldt, M. L. (1987) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.84.5.1404 · Cited by 1,189 · 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
Mitochondrial non-specific pores remain closed during cardiac ischaemia, but open upon reperfusion
Griffiths, E. J., & Halestrap, A. P. (1995) · Biochemical Journal · doi:10.1042/bj3070093 · Cited by 838 · see citing works
Mitochondrial ATP-Dependent Potassium Channels
Liu, Y., Sato, T., O'Rourke, B. P., & Marbán, E. (1998) · Circulation · doi:10.1161/01.cir.97.24.2463 · Cited by 816 · see citing works
Safranine as a probe of the mitochondrial membrane potential
Åkerman, K. E. O., & Wikström, M. K. F. (1976) · FEBS Letters · doi:10.1016/0014-5793(76)80434-6 · Cited by 793 · see citing works
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
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
Preconditioning protects ischemic rabbit heart by protein kinase C activation
Ytrehus, K., Liu, Y., & Downey, J. M. (1994) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1994.266.3.h1145 · Cited by 615 · see citing works
Mohanty, J. G., Jaffe, J. S., Schulman, E. S., & Raible, D. G. (1997) · Journal of Immunological Methods · doi:10.1016/s0022-1759(96)00244-x · Cited by 496 · see citing works
Mitochondria, the killer organelles and their weapons
Ravagnan, L., Roumier, T., & Kroemer, G. (2002) · Journal of Cellular Physiology · doi:10.1002/jcp.10111 · Cited by 484 · see citing works
Baines, C. P., Goto, M., & Downey, J. M. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0265 · Cited by 484 · cited 4× · see citing works
“Our finding that preconditioned mitochondria generate higher levels of H2O2 is in agreement with literature data showing an increase in ROS release during IP (3, 46).”
BackgroundMethodResultInfluentialATP-Sensitive Potassium Channels: A Review of their Cardioprotective Pharmacology
Grover, G. J., & Garlid, K. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1111 · Cited by 397 · 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
Murata, M., Akao, M., O'Rourke, B. P., & Marbán, E. (2001) · Circulation Research · doi:10.1161/hh2201.100205 · Cited by 365 · see citing works
Pauček, P., Mironova, G. D., Mahdi, F., Beavis, A. D., Woldegiorgis, G., & Garlid, K. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)35717-x · Cited by 357 · 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-citationPreconditioning 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
Mitochondrial ROS initiate phosphorylation of p38 MAP kinase during hypoxia in cardiomyocytes
Kulisz, A., Chen, N., Chandel, N. S., Shao, Z., & Schumacker, P. T. (2002) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00326.2001 · Cited by 287 · see citing works
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
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
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
ROS and NO trigger early preconditioning: relationship to mitochondrial K<sub>ATP</sub> 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
Mechanisms by which opening the mitochondrial ATP- sensitive K+channel protects the ischemic heart
Santos, P. D. D., Kowaltowski, A. J., Laclau, M. N., Seetharaman, S., Pauček, P., Boudina, S., Thambo, J., Tariosse, L., & Garlid, K. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00034.2002 · Cited by 221 · see citing works
Self-citationZhang, 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 complexes I, II, III, IV, and V in myocardial ischemia and autolysis
ROUSLIN, W. (1983) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1983.244.6.h743 · Cited by 200 · see citing works
Wang, Y., Hirai, K., & Ashraf, M. (1999) · Circulation Research · doi:10.1161/01.res.85.8.731 · Cited by 198 · see citing works
Mitochondrial Generation of Oxygen Radicals During Reoxygenation of Ischemic Tissues
Turrens, J. F., Beconi, M., Barilla, J., Chavez, U. B., & McCord, J. M. (1991) · Free Radical Research Communications · doi:10.3109/10715769109145847 · Cited by 177 · see citing works
Grover, G. J., McCullough, J. R., Henry, D. E., et al. (1989) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)20743-1 · Cited by 176 · see citing works
Ohnuma, Y., Miura, T., Miki, T., Tanno, M., Kuno, A., Tsuchida, A., & Shimamoto, K. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00434.2001 · Cited by 152 · see citing works
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
Effect of Bcl-2 Overexpression on Mitochondrial Structure and Function
Kowaltowski, A. J., Cosso, R. G., de Campos, C. B. L., & Fiskum, G. M. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207765200 · Cited by 138 · see citing works
Self-citationFerranti, 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-citationYao, Z., & Gross, G. J. (1993) · Circulation Research · doi:10.1161/01.res.73.6.1193 · Cited by 135 · see citing works
Role of reactive oxygen species in acetylcholine-induced preconditioning in cardiomyocytes
Yao, Z., Tong, J., Tan, X., Li, C., Shao, Z., Kim, W. C., Hoek, T. L. V., Becker, L. B., Head, C. A., & Schumacker, P. T. (1999) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.1999.277.6.h2504 · Cited by 125 · see citing works
Carroll, R. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00330-3 · Cited by 122 · see citing works
The Existence of the K+ Channel in Plant Mitochondria
Pastore, D., Stoppelli, M. C., di Fonzo, N., & Passarella, S. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.26683 · Cited by 113 · see citing works
Beavis, A. D., Lu, Y., & Garlid, K. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54032-1 · Cited by 103 · see citing works
Pauček, P., Yarov‐Yarovoy, V., Sun, X., et al. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.50.32084 · Cited by 101 · see citing works
Mammalian mitochondrial uncoupling proteins
Ježek, P., & Garlid, K. (1998) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(98)00076-4 · Cited by 99 · see citing works
Reactive oxygen species may cause myocardial reperfusion injury
Peterson, D. A., ASINGER, R. W., Elsperger, K. J., et al. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(85)80129-7 · Cited by 86 · see citing works
Alternative mitochondrial functions in cell physiopathology: beyond ATP production
Kowaltowski, A. J. (2000) · Brazilian Journal of Medical and Biological Research · doi:10.1590/s0100-879x2000000200014 · Cited by 69 · see citing works
Self-citationEffects of Nicorandil and Nifedipine on Protection of Ischemic Myocardium
Lamping, K. G., CHRISTENSEN, C. W., Pelc, L. R., et al. (1984) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-198405000-00024 · Cited by 65 · see citing works
The Mitochondrial Potassium Cycle
Garlid, K., & Pauček, P. (2001) · IUBMB Life · doi:10.1080/15216540152845948 · Cited by 59 · see citing works
ROUSLIN, W. (1983) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(83)90329-2 · Cited by 48 · 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-citationMitochondrial function during ischemic preconditioning
Crestanello, J. A., Doliba, N. M., Babsky, A. M., et al. (2002) · Surgery · doi:10.1067/msy.2002.119490 · Cited by 37 · see citing works
The ATP-Dependent Potassium Channel
Yao, Z., & Gross, G. J. (1994) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199424004-00005 · Cited by 33 · see citing works
Diazoxide induced cardioprotection: what comes first, KATP channels or reactive oxygen species?
Patel, H. H. (2001) · Cardiovascular Research · doi:10.1016/s0008-6363(01)00396-0 · Cited by 30 · see citing works
Detection of early ischemic damage by analysis of mitochondrial function in skinned fibers
Kay, L., Rossi, A., & Saks, V. A. (1997) · Springer eBooks · doi:10.1007/978-1-4615-6111-8_12 · Cited by 29 · see citing works
Detection of early ischemic damage by analysis of mitochondrial function in skinned fibers
Kay, L., Rossi, A., & Saks, V. A. (1997) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006884607272 · Cited by 26 · see citing works
Ischemic Preconditioning Improves Mitochondrial Tolerance to Experimental Calcium Overload
Crestanello, J. A., Doliba, N. M., Babsky, A. M., Doliba, N. M., Niibori, K., Whitman, G. J. R., & Osbakken, M. D. (2002) · Journal of Surgical Research · doi:10.1006/jsre.2001.6361 · Cited by 25 · see citing works
Effects of acidosis and ATP depletion on cardiac muscle electron transfer complex I
ROUSLIN, W. (1991) · Journal of Molecular and Cellular Cardiology · doi:10.1016/0022-2828(91)90202-w · Cited by 17 · see citing works
Yorikane, R., Mizuno, H., Itoh, Y., et al. (1994) · Journal of Cardiovascular Pharmacology · doi:10.1097/00005344-199407000-00006 · Cited by 10 · see citing works
Mitochondrial ATP-sensitive K+ channels increase ischemic ATP levels and prevent reperfusion injury
Belisle, E., & Kowaltowski, A. J. (2002) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(02)90752-2 · Cited by 1 · see citing works
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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-citationShiva, S., Sack, M. N., Greer, J. J., Duranski, M., Ringwood, L. A., Burwell, L., Wang, X., MacArthur, P. H., Shoja, A., Raghavachari, N., et al. (2007) · The Journal of Experimental Medicine · doi:10.1084/jem.20070198 · Cited by 555 · see citing works
Stowe, D. F., & Camara, A. K. S. (2009) · Antioxidants & Redox Signaling · doi:10.1089/ars.2008.2331 · Cited by 471 · see citing works
Chen, Q., Camara, A. K. S., Stowe, D. F., Hoppel, C. L., & Lesnefsky, E. J. (2007) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00270.2006 · Cited by 271 · see citing works
Wojtovich, A. P., & Brookes, P. S. (2008) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2008.03.025 · Cited by 119 · see citing works
Facundo, H. T. F., Carreira, R. S., de Paula, J. G., Santos, C. C. X., Ferranti, R., Laurindo, F. R. M., & Kowaltowski, A. J. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.08.041 · Cited by 72 · see citing works
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Stowe, D. F., & Riess, M. L. (2004) · Cardiovascular Drugs and Therapy · doi:10.1023/b:card.0000029082.45753.49 · Cited by 9 · see citing works
- Authors
- da Silva, M. M., Sartori, A., Belisle, E., & Kowaltowski, A. J.
- Affiliations
- Departamento de Bioquímica, Instituto de Química, Universidade de São Paulo, São Paulo SP 05508-900, Brazil
- Universidade de São Paulo (BR)
- Venue
- American Journal of Physiology-Heart and Circulatory Physiology
- Publisher
- American Physiological Society
- Published
- 2003-07
- Volume
- 285
- Issue
- 1
- Pages
- H154-H162
- ISSN
- 0363-6135 (ISSN-L)
- 1522-1539
- OpenAlex
- W2112944877
- Cited by
- 73
- References
- 57
- Citations by year
- 2022: 2 · 2021: 3 · 2018: 3 · 2017: 1 · 2016: 3 · 2015: 1 · 2014: 4 · 2013: 7 · 2012: 4
- FWCI
- 5.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Heart and Circulatory Physiology (publishedVersion)
- PubMed (publishedVersion)
- 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 respiration, hydrogen peroxide release, mitochondrial ATP-sensitive potassium channel, potassium transport, respiratory inhibition, mitochondrial complex I inhibition, reactive oxygen species, myocardial ischemia
- MeSH terms
- Adenosine Triphosphate, Animals, Biological Transport, Active, Cell Membrane, Hydrogen Peroxide, Male, Membrane Potentials, Mitochondria, Heart, Mitochondrial Swelling, Myocardium, NADP, Oxygen Consumption, Potassium, Rats, Sprague-Dawley, Reactive Oxygen Species, Ischemic Preconditioning, Rats, In Vitro Techniques
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