The complex II inhibitor atpenin A5 protects against cardiac ischemia-reperfusion injury via activation of mitochondrial KATP channels
Open accessAbstract
The cardioprotective effects of ischemic preconditioning (IPC) can be mimicked or blocked by pharmacologic agents, which modulate the mitochondrial ATP-sensitive potassium (mK(ATP)) channel, thereby implicating this channel in the mechanism of IPC. Cardioprotection can also be achieved via inhibition of mitochondrial respiratory complex II, and significant pharmacologic overlap exists between complex II inhibitors and mK(ATP) channel agonists. However, the relationship between complex II and the mK(ATP) channel remains unclear. Atpenin A5 (AA5) is a potent and specific complex II inhibitor, and herein we report that AA5 (1 nM) also activates the mK(ATP) channel and protects against simulated ischemia-reperfusion (IR) injury in isolated cardiomyocytes. Similar to known mK(ATP) agonists, AA5-mediated protection was sensitive to the mK(ATP) antagonists 5-hydroxydecanoate (5HD) and glyburide. Notably, the optimal mK(ATP) opening and protective concentration of AA5 had no effect on complex II enzymatic activity, suggesting an interaction of AA5 with complex II, but not inhibition of the complex per se, is necessary for protection. A cardioprotective effect of AA5 was also observed in isolated perfused hearts, wherein AA5 increased post-IR contractile function and decreased infarct size, in a 5HD-sensitive manner. In conclusion, the specific complex II inhibitor AA5 is the most potent mK(ATP) activator discovered to date, and provides a novel method of activating mK(ATP) channels and protecting the heart from IR injury.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
The effect of atpenin A5 was independent of complex II inhibition, and the authors suggested opening of the putative mitoKATP channel as the mechanism.
“The effect of atpenin A5 was independent of complex II inhibition, and the authors suggested that opening of the putative mitoK ATP channel is the underlying mechanism.”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [44]
Higher concentrations of atpenin A5 that inhibit complex II activity were needed in Langendorff-perfused hearts to induce cardioprotection.
“However, higher concentrations of atpenin A5that were shown to inhibit complex II activityhad to be used in Langendorf-perfused hearts to induce a cardioprotective effect [44].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [44]
Atpenin A5 had the same cardioprotective effects in cardiomyocytes and Langendorff-perfused rat hearts as ischemic preconditioning, diazoxide, and malonate.
“Importantly, the results of Wojtovich and Brookes indicate that the highly potent and specific complex II inhibitor atpenin A5 had the same cardioprotective effects in cardiomyocytes and Langendorff-perfused rat hearts as ischemic preconditioning, diazoxide, and malonate [44].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [44]
A model was presented that merges the two conflicting views, i.e., that complex II may be a component or regulator of the mitoKATP channel.
“Recently, a model was presented that merges these two conflicting views, i.e. that complex II may be a component or regulator of the mitoK ATP channel [44,156,157].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
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
Chronic systemic pesticide exposure reproduces features of Parkinson's disease
Betarbet, R., Sherer, T., Mackenzie, G., Garcia-Osuna, M., Panov, A., & Greenamyre, J. (2000) · Nature Neuroscience · doi:10.1038/81834 · Cited by 3,797 · see citing works
Mechanisms by which mitochondria transport calcium
Gunter, T. E., & Pfeiffer, D. R. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.258.5.c755 · Cited by 1,640 · see citing works
Halestrap, A. P. (2003) · Cardiovascular Research · doi:10.1016/s0008-6363(03)00533-9 · Cited by 1,223 · 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
Ferdinandy, P., Schulz, R., & Baxter, G. F. (2007) · Pharmacological Reviews · doi:10.1124/pr.107.06002 · Cited by 738 · 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
The mitochondrial origin of postischemic arrhythmias
Akar, F. G. (2005) · Journal of Clinical Investigation · doi:10.1172/jci25371 · Cited by 339 · see citing works
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
Beal, M. F., Brouillet, E., Jenkins, B. G., Henshaw, R., Rosen, B. R., & Hyman, B. T. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03633.x · Cited by 297 · see citing works
Horsefield, R., Yankovskaya, V., Sexton, G., Whittingham, W., Shiomi, K., Ōmura, S., Byrne, B., Cecchini, G., & Iwata, S. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m508173200 · Cited by 292 · 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
Direct evidence for S-nitrosation of mitochondrial complex I
Burwell, L. S., Nadtochiy, S. M., Tompkins, A. J., Young, S., & Brookes, P. S. (2006) · Biochemical Journal · doi:10.1042/bj20051435 · Cited by 274 · see citing works
Self-citationMiyadera, H., Shiomi, K., Ui, H., Yamaguchi, Y., Masuma, R., Tomoda, H., Miyoshi, H., Osanai, A., Kita, K., & Ōmura, S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0237315100 · Cited by 256 · 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
Heinzel, F. R., Luo, Y., Li, X., Boengler, K., Buechert, A., David Garcia-dorado, A., Lisa, F. D., Schulz, R., & Heusch, G. (2005) · Circulation Research · doi:10.1161/01.res.0000181171.65293.65 · Cited by 248 · see citing works
Blockade of Electron Transport during Ischemia Protects Cardiac Mitochondria
Lesnefsky, E. J., Chen, Q., Moghaddas, S., Hassan, M. O., Tandler, B., & Hoppel, C. L. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409720200 · Cited by 229 · see citing works
Ardehali, H., Chen, Z., Ko, Y., Mejía-Alvarez, R., & Marbán, E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0401703101 · Cited by 215 · see citing works
Nitroxyl affords thiol-sensitive myocardial protective effects akin to early preconditioning
Pagliaro, P., Mancardi, D., Rastaldo, R., Penna, C. R. R., Gattullo, D., Miranda, K. M., Feelisch, M., Wink, D. A., Kass, D. A., & Paolocci, N. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)01179-6 · Cited by 199 · see citing works
3-Nitropropionic acid animal model and Huntington' s disease
Borlongan, C. V., Koutouzis, T. K., & Sanberg, P. R. (1997) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(96)00027-9 · Cited by 194 · see citing works
Burwell, L. S., & Brookes, P. S. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1845 · Cited by 172 · see citing works
Self-citationMizumura, T., Nithipatikom, K., & Gross, G. J. (1995) · Circulation · doi:10.1161/01.cir.92.5.1236 · Cited by 144 · see citing works
Nadtochiy, S. M., Burwell, L. S., & Brookes, P. S. (2007) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.01.010 · Cited by 142 · see citing works
Self-citationChen, Q., Hoppel, C. L., & Lesnefsky, E. J. (2005) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.105.091702 · Cited by 140 · see citing works
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
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
Self-citationMironova, G. D., Negoda, A. E., Marinov, B. S., Pauček, P., Costa, A. D. T., Sm, G., Skarga, Y. Y., & Garlid, K. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m401115200 · Cited by 109 · see citing works
Tissue protection mediated by mitochondrial K+ channels
Facundo, H. T., Fornazari, M., & Kowaltowski, A. J. (2005) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2005.06.003 · Cited by 106 · see citing works
Targeting 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
Cardiac pharmacological preconditioning with volatile anesthetics: from bench to bedside?
Riess, M. L., Stowe, D. F., & Warltier, D. C. (2004) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00963.2003 · Cited by 102 · see citing works
Brookes, P. S., Digerness, S. B., Parks, D. A., & Darley-Usmar, V. M. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00839-0 · Cited by 93 · see citing works
Self-citationArmstrong, S. C., LIU, G., Downey, J. M., & Ganote, C. E. (1995) · Journal of Molecular and Cellular Cardiology · doi:10.1016/s0022-2828(95)90986-9 · Cited by 92 · see citing works
Diazoxide, an inhibitor of succinate oxidation
S, G., W., C. R., Porten, R., & Boj, D. (1969) · Biochemical Pharmacology · doi:10.1016/0006-2952(69)90200-7 · Cited by 84 · see citing works
Mechanisms of the interaction of nitroxyl with mitochondria
SHIVA, S., CRAWFORD, J. H., RAMACHANDRAN, A., CEASER, E. K., HILLSON, T., BROOKES, P. S., PATEL, R. P., & DARLEY-USMAR, V. M. (2004) · Biochemical Journal · doi:10.1042/bj20031758 · Cited by 78 · see citing works
Self-citationHide, E. J., & Thiemermann, C. (1996) · Cardiovascular Research · doi:10.1016/s0008-6363(96)00041-7 · Cited by 75 · see citing works
Chemical preconditioning with 3-nitropropionic acid in hearts: role of mitochondrial KATPchannel
Ockaili, R. A., Bhargava, P., & Kukreja, R. C. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.280.5.h2406 · Cited by 72 · see citing works
Is Kir6.1 a subunit of mitoKATP?
Brian Foster, D., Rucker, J. J., & Marbán, E. (2008) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.11.154 · Cited by 71 · see citing works
Bioenergetics in cardiac hypertrophy: mitochondrial respiration as a pathological target of NO·
Dai, L., Brookes, P. S., Darley-Usmar, V. M., & Anderson, P. G. (2001) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.2001.281.6.h2261 · Cited by 44 · see citing works
Self-citationAdebiyi, A., McNally, E. M., & Jaggar, J. H. (2008) · Molecular Pharmacology · doi:10.1124/mol.108.048165 · Cited by 42 · see citing works
Pu, J., Ye, B., Kroboth, S., McNally, E., Makielski, J., & Shi, N.-Q. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2007.09.010 · Cited by 41 · see citing works
Hide, E. J. (1996) · Cardiovascular Research · doi:10.1016/0008-6363(96)00041-7 · Cited by 22 · see citing works
Pasdois, P., Beauvoit, B. P., Tariosse, L., Jaspard‐Vinassa, B., Bonoron‐Adèle, S., & Santos, P. D. D. (2006) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-006-9016-3 · Cited by 16 · see citing works
Nelson Wohllk, G., Thomas, P. M., Huang, E., & Cote, G. J. (1998) · Molecular Genetics and Metabolism · doi:10.1006/mgme.1998.2752 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Kalogeris, T. J., Bao, Y., & Korthuis, R. J. (2014) · Redox Biology · doi:10.1016/j.redox.2014.05.006 · Cited by 719 · see citing works
Cardiac Mitochondria and Reactive Oxygen Species Generation
Chen, Y., & Zweier, J. L. (2014) · Circulation Research · doi:10.1161/circresaha.114.300559 · Cited by 606 · see citing works
Mitochondrial Dysfunction and Myocardial Ischemia-Reperfusion: Implications for Novel Therapies
Lesnefsky, E. J., Chen, Q., Tandler, B., & Hoppel, C. L. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010715-103335 · Cited by 443 · see citing works
Ischemia/Reperfusion Injury Revisited: An Overview of the Latest Pharmacological Strategies
Soares, R. O. D. S., Losada, D. M., Jordani, M. C., Évora, P. R. B., & Castro-e-Silva, O. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20205034 · Cited by 415 · see citing works
Superoxide generation by complex III: From mechanistic rationales to functional consequences
Bleier, L., & Dröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.002 · Cited by 369 · see citing works
Gohil, V. M., Sheth, S., Nilsson, R., Wojtovich, A. P., Lee, J. H., Perocchi, F., Chen, W., Clish, C., Ayata, C., Brookes, P., et al. (2010) · Nature Biotechnology · doi:10.1038/nbt.1606 · Cited by 191 · see citing works
Self-citationMitochondrial Channels: Ion Fluxes and More
Szabó, I., & Zoratti, M. (2014) · Physiological Reviews · doi:10.1152/physrev.00021.2013 · Cited by 321 · see citing works
Sun, Y., Lu, Y., Saredy, J., Wang, X., Drummer, C., Shao, Y., Saaoud, F., Xu, K., Liu, M., Yang, W. Y., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101696 · Cited by 283 · see citing works
Mitochondria as a Drug Target in Ischemic Heart Disease and Cardiomyopathy
Walters, A. M., Porter, G. A., Jr., & Brookes, P. S. (2012) · Circulation Research · doi:10.1161/circresaha.112.265660 · Cited by 268 · see citing works
Self-citationPfleger, J. M., He, M., & Abdellatif, M. (2015) · Cell Death and Disease · doi:10.1038/cddis.2015.202 · Cited by 251 · see citing works
SIRT3 deficiency exacerbates ischemia-reperfusion injury: implication for aged hearts
Porter, G. A., Jr., Urciuoli, W. R., Brookes, P. S., & Nadtochiy, S. M. (2014) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00027.2014 · Cited by 212 · see citing works
Self-citationRegulation of succinate dehydrogenase and role of succinate in cancer
Dalla Pozza, E., Dando, I., Pacchiana, R., Liboi, E., Scupoli, M. T., Donadelli, M., & Palmieri, M. (2020) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.04.013 · Cited by 212 · see citing works
Accumulation of Succinate in Cardiac Ischemia Primarily Occurs via Canonical Krebs Cycle Activity
Zhang, J., Wang, Y. T., Miller, J. H., Day, M. M., Munger, J. C., & Brookes, P. S. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.04.104 · Cited by 203 · see citing works
Self-citationDröse, S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2013.01.004 · Cited by 201 · see citing works
Mitochondrial complex II and reactive oxygen species in disease and therapy
Vanova, K. H., Kraus, M., Neužil, J., & Rohlena, J. (2020) · Redox Report · doi:10.1080/13510002.2020.1752002 · Cited by 162 · see citing works
Why All the Fuss about Oxidative Phosphorylation (OXPHOS)?
Xu, Y., Xue, D., Bankhead, A., & Neamati, N. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c01013 · Cited by 161 · see citing works
Itaconate modulates tricarboxylic acid and redox metabolism to mitigate reperfusion injury
Cordes, T., Lucas, A., Divakaruni, A. S., Murphy, A. N., Cabrales, P., & Metallo, C. M. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.11.019 · Cited by 153 · see citing works
Succinate metabolism: a new therapeutic target for myocardial reperfusion injury
Pell, V. R., Chouchani, E. T., Frezza, C., Murphy, M. P., & Krieg, T. (2016) · Cardiovascular Research · doi:10.1093/cvr/cvw100 · Cited by 149 · see citing works
Mitochondrial Approaches to Protect Against Cardiac Ischemia and Reperfusion Injury
Camara, A. K. S., Bienengraeber, M., & Stowe, D. F. (2011) · Frontiers in Physiology · doi:10.3389/fphys.2011.00013 · Cited by 150 · see citing works
Valls-Lacalle, L., Barba, I., Miró‐Casas, E., Alburquerque-Béjar, J. J., Ruiz‐Meana, M., Fuertes‐Agudo, M., Rodríguez‐Sinovas, A., & David Garcia-dorado, A. (2015) · Cardiovascular Research · doi:10.1093/cvr/cvv279 · Cited by 149 · see citing works
Cardioprotection by metabolic shut-down and gradual wake-up
Burwell, L. S., Nadtochiy, S. M., & Brookes, P. S. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.02.026 · Cited by 146 · see citing works
Self-citationRalph, S. J., Moreno-Sánchez, R., Neuzil, J., & Rodríguez-Enríquez, S. (2011) · Pharmaceutical Research · doi:10.1007/s11095-011-0566-7 · Cited by 126 · see citing works
Mitochondrial complex II, a novel target for anti-cancer agents
Kluckova, K., Bezawork-Geleta, A., Rohlena, J., Dong, L., & Neuzil, J. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.10.015 · Cited by 104 · see citing works
Inaoka, D. K., Shiba, T., Sato, D., Balogun, E. O., Sasaki, T. G., Nagahama, M., Oda, M., Matsuoka, S., Ohmori, J., Honma, T., et al. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms160715287 · Cited by 103 · see citing works
Moving Forwards by Blocking Back-Flow
Pell, V. R., Chouchani, E. T., Murphy, M. P., Brookes, P. S., & Krieg, T. (2016) · Circulation Research · doi:10.1161/circresaha.115.306569 · Cited by 101 · see citing works
Self-citationRedox 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-citationWang, X., Huang, X.-M., Ochs, T., Li, X., Jin, H., Tang, C., & Du, J. (2011) · Basic Research in Cardiology · doi:10.1007/s00395-011-0176-x · Cited by 101 · see citing works
The mitochondrial KATP channel—Fact or fiction?
Garlid, K., & Halestrap, A. P. (2012) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.12.011 · Cited by 85 · see citing works
Physiological consequences of complex II inhibition for aging, disease, and the mKATP channel
Wojtovich, A. P., Smith, C. O., Haynes, C. M., Nehrke, K. W., & Brookes, P. S. (2013) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2012.12.007 · Cited by 83 · see citing works
Self-citationZhang, W., & Lang, R. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1266973 · Cited by 78 · see citing works
Ischemic preconditioning: The role of mitochondria and aging
Wojtovich, A. P., Nadtochiy, S. M., Brookes, P. S., & Nehrke, K. W. (2011) · Experimental Gerontology · doi:10.1016/j.exger.2011.11.001 · Cited by 79 · see citing works
Self-citationMitochondrial Potassium Channels as Pharmacological Target for Cardioprotective Drugs
Testai, L., Rapposelli, S., Martelli, A., Breschi, M. C., & Calderone, V. (2014) · Medicinal Research Reviews · doi:10.1002/med.21332 · Cited by 74 · see citing works
SLO-2 Is Cytoprotective and Contributes to Mitochondrial Potassium Transport
Wojtovich, A. P., Sherman, T. A., Nadtochiy, S. M., Urciuoli, W. R., Brookes, P. S., & Nehrke, K. W. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028287 · Cited by 74 · see citing works
Self-citationDröse, S., Bleier, L., & Brandt, U. (2011) · Molecular Pharmacology · doi:10.1124/mol.110.070342 · Cited by 64 · see citing works
Dev, R. R., Ganji, R., Singh, S. P., Mahalingam, S., Banerjee, S., & Khosla, S. (2017) · Biochemical Journal · doi:10.1042/bcj20170258 · Cited by 64 · see citing works
Kôrge, P., John, S., Calmettes, G., & Weiss, J. N. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.768325 · Cited by 63 · see citing works
A Novel Mitochondrial KATPChannel Assay
Wojtovich, A. P., Williams, D. M., Karcz, M., Lopes, C. M. B., Gray, D. A., Nehrke, K. W., & Brookes, P. S. (2010) · Circulation Research · doi:10.1161/circresaha.109.215400 · Cited by 55 · see citing works
Self-citationPreventing mitochondrial reverse electron transport as a strategy for cardioprotection
Prag, H. A., Murphy, M. P., & Krieg, T. (2023) · Basic Research in Cardiology · doi:10.1007/s00395-023-01002-4 · Cited by 55 · see citing works
Wang, H., Huwaimel, B., Verma, K., Miller, J. E., Germain, T., Kinarivala, N., Pappas, D., Brookes, P. S., & Trippier, P. C. (2017) · ChemMedChem · doi:10.1002/cmdc.201700196 · Cited by 52 · see citing works
Self-citationWyss, R. K., Méndez‐Carmona, N., Arnold, M., Segiser, A., Mueller, M., Dutkowski, P., Carrel, T. P., & Longnus, S. (2020) · American Journal of Transplantation · doi:10.1111/ajt.16258 · Cited by 53 · see citing works
Bénit, P., Goncalves, J., El‐Khoury, R., Rak, M., Favier, J., Gimenez‐Roqueplo, A., & Rustin, P. (2022) · Biomedicines · doi:10.3390/biomedicines10081788 · Cited by 49 · see citing works
Pharmacology of Cardiac Potassium Channels
Li, G., & Dong, M. (2010) · Advances in pharmacology · doi:10.1016/s1054-3589(10)59004-5 · Cited by 48 · see citing works
Xu, J., Yang, Y., Li, X., Ding, S., Zheng, L., Xiong, C., & Yang, Y. (2023) · iMeta · doi:10.1002/imt2.124 · Cited by 46 · see citing works
Direct Activation of β-Cell KATP Channels with a Novel Xanthine Derivative
Raphemot, R., Swale, D. R., Dadi, P., Jacobson, D., Cooper, P., Wojtovich, A. P., Banerjee, S., Nichols, C., & Denton, J. (2014) · Molecular Pharmacology · doi:10.1124/mol.114.091884 · Cited by 40 · see citing works
Self-citationGuillet, V., Guéguen, N., Cartoni, R., Chevrollier, A., Desquiret‐Dumas, V., Angebault, C., Amati‐Bonneau, P., Procaccio, V., Bonneau, D., Martinou, J., et al. (2011) · The FASEB Journal · doi:10.1096/fj.10-173609 · Cited by 42 · see citing works
Wojtovich, A. P., Urciuoli, W. R., Chatterjee, S., Fisher, A. B., Nehrke, K. W., & Brookes, P. S. (2013) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00972.2012 · Cited by 41 · see citing works
Self-citationLi, C., Hu, M., Wang, Y., Lu, H., Deng, J., & Yan, X. (2015) · PubMed Central · Cited by 40 · see citing works
Milliken, A. S., Kulkarni, C. A., & Brookes, P. S. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101733 · Cited by 40 · see citing works
Self-citationPowerhouse down: Complex II dissociation in the respiratory chain
Hwang, M., Rohlena, J., Dong, L., Neužil, J., & Grimm, S. (2014) · Mitochondrion · doi:10.1016/j.mito.2014.06.001 · Cited by 39 · see citing works
Rana, A., GOYAL, N., Ahlawat, A., Jamwal, S., Reddy, B. V. K., & Sharma, S. (2014) · Perfusion · doi:10.1177/0267659114536760 · Cited by 38 · see citing works
The 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
Self-citationCellular crosstalk in cardioprotection: Where and when do reactive oxygen species play a role?
Martins‐Marques, T., Rodríguez‐Sinovas, A., & Girão, H. (2021) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2021.03.044 · Cited by 38 · see citing works
Matsuzaki, S., Szweda, P. A., Szweda, L. I., & Humphries, K. M. (2009) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2009.05.008 · Cited by 35 · see citing works
A non-cardiomyocyte autonomous mechanism of cardioprotection involving the SLO1 BK channel
Wojtovich, A. P., Nadtochiy, S. M., Urciuoli, W. R., Smith, C. O., Grunnet, M., Nehrke, K. W., & Brookes, P. S. (2013) · PeerJ · doi:10.7717/peerj.48 · Cited by 35 · see citing works
Self-citationKotla, S., Zhang, A., Imanishi, M., Ko, K. A., Lin, S. H., Gi, Y. J., Moczygemba, M. M., Isgandarova, S., Schadler, K., Chung, C. D., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102132 · Cited by 36 · see citing works
Self-citationKoenitzer, J. R., Bonacci, G., Woodcock, S. R., Chen, C.-S., Cantú‐Medellín, N., Kelley, E. E., & Schopfer, F. J. (2015) · Redox Biology · doi:10.1016/j.redox.2015.11.002 · Cited by 35 · see citing works
Inhibition of succinate-linked respiration and complex II activity by hydrogen peroxide
Moser, M. D., Matsuzaki, S., & Humphries, K. M. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.06.009 · Cited by 32 · see citing works
Wojtovich, A. P., Wei, A. Y., Sherman, T. A., Foster, T. H., & Nehrke, K. W. (2016) · Scientific Reports · doi:10.1038/srep29695 · Cited by 34 · see citing works
Self-citationDong, L., & Neužil, J. (2014) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-394625-6.00008-8 · Cited by 33 · see citing works
Mozaffari, M. S., Baban, B., Liu, J. Y., Abebe, W., Sullivan, J. C., & Elmarakby, A. A. (2011) · Basic Research in Cardiology · doi:10.1007/s00395-011-0150-7 · Cited by 31 · see citing works
Multidimensional Regulation of Cardiac Mitochondrial Potassium Channels
Kulawiak, B., Bednarczyk, P., & Szewczyk, A. M. (2021) · Cells · doi:10.3390/cells10061554 · Cited by 30 · see citing works
Pravdić, D., Hirata, N., Barber, L., Sedlić, F., Bosnjak, Z. J., & Bienengraeber, M. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.07.003 · Cited by 28 · see citing works
Krautwald, S., Nilewski, C., Mori, M., Shiomi, K., Ōmura, S., & Carreira, E. M. (2016) · Angewandte Chemie International Edition · doi:10.1002/anie.201511672 · Cited by 28 · see citing works
Logan, S. J., Yin, L., Geldenhuys, W. J., Enrick, M., Stevanov, K., Carroll, R. T., Ohanyan, V. A., Kolz, C. L., & Chilian, W. M. (2015) · Basic Research in Cardiology · doi:10.1007/s00395-015-0471-z · Cited by 27 · see citing works
A Cell-Based Phenotypic Assay to Identify Cardioprotective Agents
Guo, S., Olm-Shipman, A. J., Walters, A. M., Urciuoli, W. R., Devito, S., Nadtochiy, S. M., Wojtovich, A. P., & Brookes, P. S. (2012) · Circulation Research · doi:10.1161/circresaha.111.263715 · Cited by 27 · see citing works
Self-citationMao, Z., Liu, W., Huang, Y., Sun, T., Bao, K., Feng, J., Moskalev, A., Hu, Z., & Li, J. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.08.007 · Cited by 26 · see citing works
Kamarauskaitė, J., Banienė, R., Trumbeckas, D., Strazdauskas, A., & Trumbeckaitė, S. (2021) · Antioxidants · doi:10.3390/antiox10050747 · Cited by 24 · see citing works
Wojtovich, A. P., DiStefano, P. S., Sherman, T., Brookes, P. S., & Nehrke, K. W. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.01.021 · Cited by 22 · see citing works
Self-citationCardiomyocyte sulfonylurea receptor 2-KATPchannel mediates cardioprotection and ST segment elevation
Stoller, D. A., Fahrenbach, J. P., Chalupský, K., Tan, B., Aggarwal, N. T., Metcalfe, J., Hadhazy, M., Shi, N., Makielski, J. C., & McNally, E. M. (2010) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00084.2010 · Cited by 22 · see citing works
Lee, K. H., Lee, S., Cho, H., Woo, J. S., Kang, J. H., Jeong, Y., Cheng, X. W., Kim, W.-S., & Kim, W. (2017) · PLoS ONE · doi:10.1371/journal.pone.0180207 · Cited by 22 · see citing works
Jeon, Y. H., He, M., Austin, J., Shin, H., Pfleger, J. M., & Abdellatif, M. (2020) · Cellular Signalling · doi:10.1016/j.cellsig.2020.109866 · Cited by 19 · see citing works
Wojtovich, A. P., Nehrke, K. W., & Brookes, P. S. (2010) · Acta Biochimica Polonica · doi:10.18388/abp.2010_2429 · Cited by 19 · see citing works
Self-citationCatalytic Asymmetric Synthesis of Ketene Heterodimer β-Lactones: Scope and Limitations
Chen, S., Ibrahim, A., Peraino, N. J., Nalla, D., Mondal, M., Raaphorst, M. V., & Kerrigan, N. J. (2016) · The Journal of Organic Chemistry · doi:10.1021/acs.joc.6b01481 · Cited by 17 · see citing works
Alternative Targets for Modulators of Mitochondrial Potassium Channels
Wrzosek, A., Gałecka, S., Żochowska, M., Olszewska, A., & Kulawiak, B. (2022) · Molecules · doi:10.3390/molecules27010299 · Cited by 15 · see citing works
Sun, P., Sun, S., Kong, W., & Li, S. (2025) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.4c02757 · Cited by 14 · see citing works
Repeated Exposure to Hyperbaric Hyperoxia Affects Mitochondrial Functions of the Lung Fibroblasts
Dejmek, J., Kohoutová, M., Kripnerová, M., Čedíková, M., Tůma, Z., Babuška, V., Bolek, L., & Kuncová, J. (2018) · Physiological Research · doi:10.33549/physiolres.934046 · Cited by 14 · see citing works
Aberrant ER-mitochondria communication is a common pathomechanism in mitochondrial disease
Morcillo, P., Kabra, K., VELASCO, K. R., Cordero, H., Jennings, S., Yun, T. D., Larrea, D., Akman, H. O., & Schon, E. A. (2024) · Cell Death and Disease · doi:10.1038/s41419-024-06781-9 · Cited by 13 · see citing works
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
Gori, D. N. P., Ruatta, S., Fló, M., Alberca, L. N., Bellera, C. L., Park, S., Heo, J., Lee, H., Park, K.-H. P., Pritsch, O., et al. (2023) · Frontiers in Drug Discovery · doi:10.3389/fddsv.2022.1082065 · Cited by 9 · see citing works
Fan, Z., Wen, T., Chen, Y., Huang, L., Lin, W., Yin, C., & Tan, W. (2016) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/6362812 · Cited by 9 · see citing works
Onukwufor, J. O., Stevens, D., & Kamunde, C. (2016) · Journal of Experimental Biology · doi:10.1242/jeb.140186 · Cited by 8 · see citing works
Савченко, Л. В., Martinelli, I., Marsal, D. J., Ждан, В. М., Tao, J., & Kunduzova, O. (2023) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2023.1205893 · Cited by 7 · see citing works
LC-MS Analysis of Human Platelets as a Platform for Studying Mitochondrial Metabolism
Worth, A. J., Marchione, D. M., Parry, R. C., Wang, Q., Gillespie, K. P., Saillant, N. N., Sims, C. A., Mesaros, C., Snyder, N. W., & Blair, I. A. (2016) · Journal of Visualized Experiments · doi:10.3791/53941 · Cited by 7 · see citing works
Krautwald, S., Nilewski, C., Mori, M., Shiomi, K., Ōmura, S., & Carreira, E. M. (2016) · Angewandte Chemie · doi:10.1002/ange.201511672 · Cited by 7 · see citing works
Mu, F., Zhang, H., Gong, R., Lin, R. J., Zhao, M., Tao, X., Shang, L., Xi, M., Zhao, J., & Wang, J. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103932 · Cited by 7 · see citing works
Wan, X., Zhao, J., & Xie, J. (2012) · Journal of Huazhong University of Science and Technology [Medical Sciences] · doi:10.1007/s11596-012-0083-x · Cited by 5 · see citing works
Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral DrugsPreprint
Renz, A., Hohner, M., Breitenbach, M., Josephs‐Spaulding, J., Dürrwald, J., Best, L., Jami, R., Μαρίνος, Γ., Cabreiro, F., Dräger, A., et al. (2022) · Preprints.org · doi:10.20944/preprints202210.0223.v1 · Cited by 4 · see citing works
Belyaeva, E. A. (2023) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2023.114829 · Cited by 5 · see citing works
Acetylation in Cardiac Aging: Molecular Mechanism and Therapeutic Approaches
Hase, A. D., & Banerjee, S. (2025) · Results and problems in cell differentiation · doi:10.1007/978-3-031-91459-1_9 · Cited by 3 · see citing works
Renz, A., Hohner, M., Jami, R., Breitenbach, M., Josephs‐Spaulding, J., Dürrwald, J., Best, L., Dulière, V., Mialon, C., Bader, S. M., et al. (2025) · Communications Biology · doi:10.1038/s42003-025-08148-y · Cited by 4 · see citing works
ATP-sensitive K(+)-channels in muscle cells: features and physiological role
Vadzyuk, O. B. (2014) · The Ukrainian Biochemical Journal · doi:10.15407/ubj86.03.005 · Cited by 3 · see citing works
Sack, M. N., Murphy, E., & Schulz, R. (2009) · Basic Research in Cardiology · doi:10.1007/s00395-009-0005-7 · Cited by 2 · see citing works
Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral DrugsPreprint
Renz, A., Hohner, M., Breitenbach, M., Josephs‐Spaulding, J., Dürrwald, J., Best, L., Jami, R., Μαρίνος, Γ., Cabreiro, F., Dräger, A., et al. (2023) · Preprints.org · doi:10.20944/preprints202210.0223.v2 · Cited by 1 · see citing works
ISCHEMIC PRECONDITIONING AND POSTCONDITIONING IN CARDIOVASCULAR SURGERY
Şengül, İ., & Şengül, D. (2010) · DergiPark (Istanbul University) · Cited by 1 · see citing works
Metabolic Modeling Elucidates Phenformin and Atpenin A5 as Broad-Spectrum Antiviral DrugsPreprint
Renz, A., Hohner, M., Breitenbach, M., Josephs‐Spaulding, J., Dürrwald, J., Best, L., Dulière, V., Mialon, C., Bader, S. M., Jami, R., et al. (2024) · Preprints.org · doi:10.20944/preprints202210.0223.v3 · Cited by 1 · see citing works
Wojtovich, A. P., Nehrke, K. W., & Brookes, P. S. (2010)
Self-citationpreconditioningfor cardioprotection by ischemic channel but is ATP
Nehrke, K. W., Brookes, P. S., Wojtovich, A. P., Urciuoli, W. R., Chatterjee, S., & Fisher, A. B. (2013)
Self-citationMilliken, A. S., Kulkarni, C. A., & Brookes, P. S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.08.31.275438
Self-citation
- Authors
- Wojtovich, A. P., & Brookes, P. S.
- Affiliations
- University of Rochester Medicine (US)
- Corresponding author
- Brookes, Paul S.
- Venue
- Basic Research in Cardiology
- Published
- 2009-02-26
- Volume
- 104
- Issue
- 2
- Pages
- 121-129
- ISSN
- 0003-9217 (ISSN-L)
- 0300-8428
- 1435-1803
- PMC
- PMC2776710
- OpenAlex
- W2092473885
- Cited by
- 107
- References
- 45
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 2 · 2023: 7 · 2022: 3 · 2021: 5 · 2020: 7 · 2019: 3 · 2018: 2 · 2017: 5 · 2016: 10 · 2015: 6 · 2014: 10 · 2013: 9 · 2012: 8
- FWCI
- 7.04
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Basic Research in Cardiology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (R01HL071158)
- 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
- complex II inhibition, mitochondrial ATP-sensitive potassium channel, myocardial ischemia-reperfusion injury, cardioprotection, ischemic preconditioning, 5-hydroxydecanoate, glibenclamide, mitochondrial respiration, infarct size, cardiomyocytes
- MeSH terms
- Animals, Anti-Arrhythmia Agents, Decanoic Acids, Hydroxy Acids, Male, Mitochondria, Heart, Pyridones, Potassium Channels, Myocardial Reperfusion Injury, Rats, Sprague-Dawley, Cytoprotection, Myocytes, Cardiac, Electron Transport Complex II, 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
