Molecular and Cellular Biochemistry

, Volume 337, Issue 1, pp 25–38

Opening of the mitoKATP channel and decoupling of mitochondrial complex II and III contribute to the suppression of myocardial reperfusion hyperoxygenation

  • Bin Liu
  • Xuehai Zhu
  • Chwen-Lih Chen
  • Keli Hu
  • Harold M. Swartz
  • Yeong-Renn Chen
  • Guanglong He
Article

DOI: 10.1007/s11010-009-0283-2

Cite this article as:
Liu, B., Zhu, X., Chen, CL. et al. Mol Cell Biochem (2010) 337: 25. doi:10.1007/s11010-009-0283-2

Abstract

Diazoxide, a mitochondrial ATP-sensitive potassium (mitoKATP) channel opener, protects the heart from ischemia–reperfusion injury. Diazoxide also inhibits mitochondrial complex II-dependent respiration in addition to its preconditioning effect. However, there are no prior studies of the role of diazoxide on post-ischemic myocardial oxygenation. In the current study, we determined the effect of diazoxide on the suppression of post-ischemic myocardial tissue hyperoxygenation in vivo, superoxide (O2−•) generation in isolated mitochondria, and impairment of the interaction between complex II and complex III in purified mitochondrial proteins. It was observed that diazoxide totally suppressed the post-ischemic myocardial hyperoxygenation. With succinate but not glutamate/malate as the substrate, diazoxide significantly increased ubisemiquinone-dependent O2−• generation, which was not blocked by 5-HD and glibenclamide. Using a model system, the super complex of succinate-cytochrome c reductase (SCR) hosting complex II and complex III, we also observed that diazoxide impaired complex II and its interaction with complex III with no effect on complex III. UV–visible spectral analysis revealed that diazoxide decreased succinate-mediated ferricytochrome b reduction in SCR. In conclusion, our results demonstrated that diazoxide suppressed the in vivo post-ischemic myocardial hyperoxygenation through opening the mitoKATP channel and ubisemiquinone-dependent O2−• generation via inhibiting mitochondrial complex II-dependent respiration.

Keywords

MitochondriaDiazoxideSuperoxideIschemia reperfusionOxygenation

Abbreviations

DCPIP

Dichlorophenolindophenol

DEPMPO

5-(Diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide

DMPO

5,5-Dimethyl-1-pyrroline N-oxide

DTPA

Diethylenetriaminepentaacetic acid

EPR

Electron paramagnetic resonance

FCCP

Carbonyl cyanide-p-tri-fluromethoxyphenyl-hydrazone

5-HD

5-hydroxydecanoate

H2DCF

2′,7′-dichlorodihydrofluorescein

IPC

Ischemic preconditioning

mitoKATP

Mitochondrial ATP-sensitive potassium channel

3-NPA

3-Nitropropionic acid

O2−•

Superoxide

OH

Hydroxyl radical

\( P_{{{\text{O}}_{ 2} }} \)

Tissue oxygen tension

PPC

Pharmacological preconditioning

Q

Ubiquinone

Q−•

Ubisemiquinone

Q2

Ubiquinone-2

QCR

Ubiquinol cytochrome c reductase or complex III

QH2

Ubiquinol

QO−•

Ubisemiquinone at the QO site

ROS

Reactive oxygen species

SCR

Succinate-cytochrome c reductase or super complex containing complex II and complex III

SMP

Sub-mitochondrial particles

SOD

Superoxide dismutase

SQR

Succinate ubiquinone reductase or complex II

TEA+

Tetraethyl ammonium

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Bin Liu
    • 1
    • 2
  • Xuehai Zhu
    • 3
  • Chwen-Lih Chen
    • 4
  • Keli Hu
    • 5
  • Harold M. Swartz
    • 6
  • Yeong-Renn Chen
    • 4
  • Guanglong He
    • 7
    • 8
  1. 1.The Center for Biomedical EPR Spectroscopy and ImagingDavis Heart and Lung Research InstituteColumbusUSA
  2. 2.Shantou University Medical CollegeShantouChina
  3. 3.Key Laboratory of Organ TransplantationMinistry of Education Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and TechnologyWuhanChina
  4. 4.Davis Heart and Lung Research InstituteColumbusUSA
  5. 5.Division of Pharmacology, College of PharmacyThe Ohio State UniversityColumbusUSA
  6. 6.The EPR Center for the Study of Viable SystemsDartmouth Medical SchoolHanoverUSA
  7. 7.The Center for Biomedical EPR Spectroscopy and ImagingDavis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal MedicineColumbusUSA
  8. 8.Davis Heart and Lung Research Institute, Division of Cardiovascular MedicineDepartment of Internal MedicineColumbusUSA