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K+-independent Actions of Diazoxide Question the Role of Inner Membrane KATP Channels in Mitochondrial Cytoprotective Signaling
Open accessAbstract
Activation by diazoxide and inhibition by 5-hydroxydecanoate are the hallmarks of mitochondrial ATP-sensitive K+ (K(ATP)) channels. Opening of these channels is thought to trigger cytoprotection (preconditioning) through the generation of reactive oxygen species. However, we found that diazoxide-induced oxidation of the widely used reactive oxygen species indicator 2',7'-dichlorodihydrofluorescein in isolated liver and heart mitochondria was observed in the absence of ATP or K+ and therefore independent of K(ATP) channels. The response was blocked by stigmatellin, implying a role for the cytochrome bc1 complex (complex III). Diazoxide, though, did not increase hydrogen peroxide (H2O2) production (quantitatively measured with Amplex Red) in intact mitochondria, submitochondrial particles, or purified cytochrome bc1 complex. We confirmed that diazoxide inhibited succinate oxidation, but it also weakly stimulated state 4 respiration even in K+-free buffer, excluding a role for K(ATP) channels. Furthermore, we have shown previously that 5-hydroxydecanoate is partially metabolized, and we hypothesized that fatty acid metabolism may explain the ability of this putative mitochondrial K(ATP) channel blocker to inhibit diazoxide-induced flavoprotein fluorescence, commonly used as an assay of K(ATP) channel activity. Indeed, consistent with our hypothesis, we found that decanoate inhibited diazoxide-induced flavoprotein oxidation. Taken together, our data question the "mitochondrial K(ATP) channel" hypothesis of preconditioning. Diazoxide did not evoke superoxide (which dismutates to H2O2) from the respiratory chain by a direct mechanism, and the stimulatory effects of this compound on mitochondrial respiration and 2',7'-dichlorodihydrofluorescein oxidation were not due to the opening of K(ATP) channels.
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“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 [129]
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“Diazoxide inhibits complex II [128,129,147], while the K ATP channel antagonist 5-HD can be metabolized by the ß-oxidation pathway of the mitochondria [148][149][150].”
From Differential effects of complex II on mitochondrial ROS production and their relation to cardioprotective pre- and postconditioning (2013) · cites this paper as [129]
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Zhou, M., Diwu, Z. J., Panchuk-Voloshina, N., & Haugland, R. P. (1997) · Analytical Biochemistry · doi:10.1006/abio.1997.2391 · Cited by 1,400
Preconditioning the myocardium: from cellular physiology to clinical cardiology
YELLON, D. M., & DOWNEY, J. M. (2003) · Physiological Reviews · doi:10.1152/physrev.00009.2003 · Cited by 1,062
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
Hempel, S. L., Buettner, G. R., O’Malley, Y. Q., Wessels, D. A., & Flaherty, D. M. (1999) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(99)00061-1 · Cited by 740
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
Methods of Detection of Vascular Reactive Species
Tarpey, M. M., & Fridovich, I. (2001) · Circulation Research · doi:10.1161/hh1501.094365 · Cited by 554
Ping, P., Zhang, J., Qiu, Y., Tang, X., Manchikalapudi, S., Cao, X., & Bolli, R. (1997) · Circulation Research · doi:10.1161/01.res.81.3.404 · Cited by 482
Smith, A. L. (1967) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(67)10016-5 · Cited by 460
The Mitochondrial K Channel as a Receptor for Potassium Channel Openers
Garlid, K., Pauček, P., Yarov-Yarovoy, V. M., Sun, X., & Schindler, P. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8796 · Cited by 445
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
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Research works printed but not linked: 4
- Wang, 2001, Am. J. Physiol., 280, H246
- Costa, 2006, Am. J. Physiol., 290, H406
- Okun, 1999, J. Biochem., 274, 2625
- Kowaltowski, 2001, Am. J. Physiol., 280, H649
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Ferdinandy, P., Schulz, R., & Baxter, G. F. (2007) · Pharmacological Reviews · doi:10.1124/pr.107.06002 · Cited by 752
Molecular Mechanisms of Superoxide Production by the Mitochondrial Respiratory Chain
Dröse, S., & Brandt, U. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3573-0_6 · Cited by 537
Self-citationCrosstalk signaling between mitochondrial Ca2+ and ROS
Robert, F. F. (2009) · Frontiers in bioscience · doi:10.2741/3303 · Cited by 448
The mechanism of mitochondrial superoxide production by the cytochrome bc1 complex
Dröse, S., & Brandt, U. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m803236200 · Cited by 386
Self-citationHaendeler, J., Dröse, S., Büchner, N., Jakob, S., Altschmied, J., Goy, C., Spyridopoulos, I., Zeiher, A. M., Brandt, U., & Dimmeler, S. (2009) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.109.185546 · Cited by 375
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Metadata
- Authors
- Dröse, S., Brandt, U., & Hanley, P. J.
- Affiliations
- University Hospital Frankfurt (DE)
- Philipps University of Marburg (DE)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2006-08
- Volume
- 281
- Issue
- 33
- Pages
- 23733-23739
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2066735039
- Cited by
- 105
- References
- 30
- Citations by year
- 2025: 1 · 2024: 1 · 2023: 3 · 2022: 2 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 4 · 2015: 2 · 2014: 4 · 2013: 7 · 2012: 9
- FWCI
- 5.71
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) (submittedVersion, cc-by)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Ischemia and Reperfusion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › ATP Synthase and ATPases Research
- Keywords
- diazoxide, mitochondrial ATP-sensitive potassium channel, 5-hydroxydecanoate, cytochrome bc1 complex, cytoprotection, reactive oxygen species, superoxide, hydrogen peroxide, succinate oxidation, mitochondrial respiration, stigmatellin, liver mitochondria, heart mitochondria, fatty acid metabolism
- MeSH terms
- Animals, Cattle, Cells, Cultured, Decanoic Acids, Diazoxide, Flavoproteins, Glucose, Hydroxy Acids, Intracellular Membranes, Mitochondria, Heart, Mitochondria, Liver, Oxidation-Reduction, Oxidoreductases, Submitochondrial Particles, Uncoupling Agents, Potassium Channels, Signal Transduction, Culture Media, Conditioned, Potassium Channel Blockers, Myocytes, Cardiac, Rats
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