Dinitrophenol Pretreatment of Rat Ventricular Myocytes Protects Against Damage by Metabolic Inhibition and Reperfusion

Rodrigo, Glenn C.; Lawrence, Chris L.; Standen, N B

doi:10.1006/jmcc.2002.1536

Cited by 48 publications

(69 citation statements)

References 38 publications

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“…The spectrum in figure 1d was taken on an isolated cardiomyocyte using a 488 nm-laser power of 0.9 mW for 30 s. We have also recorded a single spectrum from a cardiomyocyte with a shorter exposure time of 1 s. Although the intensity of n 4 was close to the noise level in this spectrum, the band position was still identified as rsif.royalsocietypublishing.org J. R. Soc. Interface 12: 20141339 centred at 1356 cm 21 . The effects of long-term exposure to 488 nm radiation were also examined by recording a sequence of 20 spectra (0.9 mW, 30 s) from an isolated cardiomyocyte at 5 min intervals.…”

Section: Hyperoxia In An Isolated Cardiomyocytementioning

confidence: 99%

“…Because of the significant p-backbonding to the porphyrin ring, n 4 has a relatively low wavenumber (approx. 1355 cm 21 ). When an oxygen molecule binds reversibly to the sixth-coordinate position of the ferrous metal ion in myoglobin, a complex is formed with a bent Fe-O -O geometry.…”

Section: Introductionmentioning

confidence: 96%

“…Following isolation, myocytes were stored in Tyrode solution at room temperature (approx. 218C) at a density of about 0.4 million myocytes ml 21 …”

mentioning

confidence: 99%

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Spectroscopic analysis of myoglobin and cytochrome c dynamics in isolated cardiomyocytes during hypoxia and reoxygenation

Almohammedi

Kapetanaki

Wood

et al. 2015

J. R. Soc. Interface.

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Raman microspectroscopy was applied to monitor the intracellular redox state of myoglobin and cytochrome c from isolated adult rat cardiomyocytes during hypoxia and reoxygenation. The nitrite reductase activity of myoglobin leads to the production of nitric oxide in cells under hypoxic conditions, which is linked to the inhibition of mitochondrial respiration. In this work, the subsequent reoxygenation of cells after hypoxia is shown to lead to increased levels of oxygen-bound myoglobin relative to the initial levels observed under normoxic conditions. Increased levels of reduced cytochrome c in ex vivo cells are also observed during hypoxia and reoxygenation by Raman microspectroscopy. The cellular response to reoxygenation differed dramatically depending on the method used in the preceding step to create hypoxic conditions in the cell suspension, where a chemical agent, sodium dithionite, leads to reduction of cytochromes in addition to removal of dissolved oxygen, and bubbling-N 2 gas leads to displacement of dissolved oxygen only. These results have an impact on the assessment of experimental simulations of hypoxia in cells. The spectroscopic technique employed in this work will be used in the future as an analytical method to monitor the effects of varying levels of oxygen and nutrients supplied to cardiomyocytes during either the preconditioning of cells or the reperfusion of ischaemic tissue.

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Section: Hyperoxia In An Isolated Cardiomyocytementioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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Spectroscopic analysis of myoglobin and cytochrome c dynamics in isolated cardiomyocytes during hypoxia and reoxygenation

Almohammedi

Kapetanaki

Wood

et al. 2015

J. R. Soc. Interface.

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“…Measurements of ROS formation at high Ψm values were performed in isolated mitochondria and were additionally confirmed in cultured cells 43, 44, 45. Normally, in isolated mitochondria and in reconstituted cytochrome c oxidase 46, which is the terminal enzyme of the mitochondrial respiratory chain, high values (140–200 mV) of Ψm are observed.…”

Section: Ros Have Double Functionsmentioning

confidence: 87%

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

et al. 2016

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Mitochondrial respiration is the predominant source of ATP. Excessive rates of electron transport cause a higher production of harmful reactive oxygen species (ROS). There are two regulatory mechanisms known. The first, according to Mitchel, is dependent on the mitochondrial membrane potential that drives ATP synthase for ATP production, and the second, the Kadenbach mechanism, is focussed on the binding of ATP to Cytochrome c Oxidase (CytOx) at high ATP/ADP ratios, which results in an allosteric conformational change to CytOx, causing inhibition. In times of stress, ATP‐dependent inhibition is switched off and the activity of CytOx is exclusively determined by the membrane potential, leading to an increase in ROS production. The second mechanism for respiratory control depends on the quantity of electron transfer to the Heme aa3 of CytOx. When ATP is bound to CytOx the enzyme is inhibited, and ROS formation is decreased, although the mitochondrial membrane potential is increased.

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“…Rodrigo et al showed that DNP depolarises the mitochondrial membrane and decreases nicotinamide adenine dinucleotide (NADH) in isolated cardiomyocyte models whilst conferring protection from metabolic inhibition and reperfusion. 6 Another notable class of cardioprotective agents are chemical drugs that release nitric oxide (NO). [7][8][9] Endogenous production of NO is already known to play a role in cardioprotection.…”

Section: Introductionmentioning

confidence: 99%

Monitoring Changes in the Redox State of Myoglobin in Cardiomyocytes by Raman Spectroscopy Enables the Protective Effect of NO Donors to Be Evaluated

Almohammedi¹,

Kapetanaki²,

Hudson³

et al. 2015

Anal. Chem.

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Raman microspectroscopy has been used to monitor changes in the redox and ligandcoordination states of the heme complex in myoglobin during the pre-conditioning of ex vivo cardiomyocytes with pharmacological drugs that release nitric oxide (NO). These chemical agents are known to confer protection on heart tissue against ischemia-reperfusion injury.Subsequent changes in the redox and ligand-coordination states during experimental simulations of ischemia and reperfusion have also been monitored. We found that these measurements, in real time, could be used to evaluate the pre-conditioning treatment of cardiomyocytes, and predict the likelihood of cell survival following a potentially-lethal period of ischemia.Evaluation of the pre-conditioning treatment was done at the single-cell level. The binding of NO to myoglobin, giving a 6-coordinate ferrous-heme complex, was inferred from the measured Raman bands of a cardiomyocyte by comparison to pure solution of the protein in the presence of NO. A key change in the Raman spectrum was observed after perfusion of the NO-donor was completed, where if the pre-conditioning treatment was successful then the bands corresponding to the nitrosyl complex were replaced by bands corresponding to metmyoglobin, Mb III . An observation of Mb III bands in the Raman spectrum was made for all the cardiomyocytes that recovered contractile function, whilst the absence of Mb III bands always indicated that the cardiomyocyte would be unable to recover contractile function, following the simulated conditions of ischemia and reperfusion in these experiments.3

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Dinitrophenol Pretreatment of Rat Ventricular Myocytes Protects Against Damage by Metabolic Inhibition and Reperfusion

Cited by 48 publications

References 38 publications

Spectroscopic analysis of myoglobin and cytochrome c dynamics in isolated cardiomyocytes during hypoxia and reoxygenation

Spectroscopic analysis of myoglobin and cytochrome c dynamics in isolated cardiomyocytes during hypoxia and reoxygenation

Revisiting Kadenbach: Electron flux rate through cytochrome c‐oxidase determines the ATP‐inhibitory effect and subsequent production of ROS

Monitoring Changes in the Redox State of Myoglobin in Cardiomyocytes by Raman Spectroscopy Enables the Protective Effect of NO Donors to Be Evaluated

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