[7] Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios

Estabrook, Ronald W.

doi:10.1016/0076-6879(67)10010-4

Cited by 1,555 publications

(654 citation statements)

References 12 publications

Supporting

Mentioning

638

Contrasting

Unclassified

Order By: Relevance

“…The mitochondria from the liver were isolated by differential centrifugation using a literature procedure [42]. The effect of 2a and 2d on the consumption of oxygen in mitochondria was measured by polarography by a previously reported methodology [43]. In these measurements, freshly isolated mitochondria were incubated at 30 °C in a respiratory buffer of 125 mM sucrose, 65 mM KCl, 10 mM HEPES, 5 mM potassium phosphate, 1 mM MgCl 2 , pH 7.2 containing 5 mM succinate as respiratory substrate.…”

Section: Evaluation Of 2a and 2d On Respiration In Rat Liver Mitochonmentioning

confidence: 99%

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Pati

Das

et al. 2009

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

This study demonstrated that replacement of the axial protons on the C2 and C6 atoms of various 1-methyl-3,5-bis(benzylidene)-4-piperidones 3 by a dimethylene bridge leading to series 2 lowered cytotoxic potencies. Four compounds 2a and 3a-c emerged as lead molecules based on their toxicity towards different neoplasms and their selective toxicity for malignant rather than normal cells. Some possible reasons for the disparity between the IC 50 values in the two series of compounds are presented based on molecular modeling, log P values and respiration in rat liver mitochondria.

show abstract

Section: Evaluation Of 2a and 2d On Respiration In Rat Liver Mitochonmentioning

confidence: 99%

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Pati

Das

et al. 2009

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

show abstract

“…Oxygen consumption by the brain mitochondria was registered polarographically with a Clark oxygen electrode [16] connected to a suitable recorder in a thermostated water-jacketed closed chamber with magnetic stirring. The reactions were carried out at 30°C in 1 ml of the standard medium (100 mM sucrose, 100 mM KCl, 2 mM KH 2 PO 4 , 5 mM Hepes, and 10 μM EGTA, pH 7.4) with 0.8 mg of protein.…”

Section: Mitochondrial Respiration Measurementsmentioning

confidence: 99%

Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage

Cardoso

Santos

Carvalho

et al. 2008

Free Radical Biology and Medicine

View full text Add to dashboard Cite

This study was aimed at investigating the effects of subchronic administration of doxorubicin (DOX) on brain mitochondrial bioenergetics and oxidative status. Rats were treated with seven weekly injections of vehicle (sc, saline solution) or DOX (sc, 2 mg kg −1 ), and 1 week after the last administration of the drug the animals were sacrificed and brain mitochondrial fractions were obtained. Several parameters were analyzed: respiratory chain, phosphorylation system, induction of the permeability transition pore (PTP), mitochondrial aconitase activity, lipid peroxidation markers, and nonenzymatic antioxidant defenses. DOX treatment induced an increase in thiobarbituric acid-reactive substances and vitamin E levels and a decrease in reduced glutathione content and aconitase activity. Furthermore, DOX potentiated PTP induced by Ca 2+ . No statistical differences were observed in the other parameters analyzed. Altogether our results show that DOX treatment increases the susceptibility of brain mitochondria to Ca 2+ -induced PTP opening and oxidative stress, predisposing brain cells to degeneration and death.© 2008 Elsevier Inc. All rights reserved. IntroductionDoxorubicin (DOX) is a potent broad-spectrum antineoplastic agent effective in the treatment of a wide variety of cancers, including both solid tumors and leukemias [1]. However, the chronic administration of this drug can induce toxicity to nontarget tissues, cardiotoxicity being the best known side effect [2]. DOX-induced cardiotoxicity has been attributed to a number of effects, including the direct inhibition of key transporters involved in ion homeostasis, alterations in cellular iron and calcium metabolism, disruption of sarcoplasmic reticulum function, mitochondrial dysfunction, and apoptotic cell loss [3]. The mechanisms underlying these events seem to be linked to an increased production of reactive oxygen species (ROS) and oxidative damage [3]. Oxidative stress results from an imbalance between the generation of ROS and reactive nitrogen species and their removal by the cellular antioxidant system [4] and has been implicated in many neurodegenerative disorders [5,6].Several studies in breast cancer survivors and other patients undergoing DOX-based chemotherapy have reported persistent changes in cognitive functions, including memory loss and difficulty in the performance of daily life tasks [4]. Despite the well-known side effects of DOX treatment in the heart, little is known about its effects in the brain. Park et al. [7] showed that DOX generates free radicals in cultured astrocytes and decreases cell viability in a concentration-dependent manner. Similarly, in a study made in primary neuronal cultures, Lopes et al. [2] observed that DOX can induce neuronal cell death by necrosis and apoptosis in a concentration-dependent manner.Mitochondria play a central role in both cell life and cell death [8]. These organelles are essential for the production of ATP through oxidative phosphorylation and regulation of intracellular Ca 2+ homeostasis and are t...

show abstract

“…ADP was added to initiate state 3 oxidation. Evaluation of states 3 and 4, respiratory control ratio (RCR) and oxidative phosphorylation (ADP:O) were essentially done according to Estabrook (1967), assuming an oxygen concentration of 0.253 µmol/ml (O 2 ) under the conditions described above.…”

Section: Synthesis Of At Pmentioning

confidence: 99%

Valproate inhibits the mitochondrial pyruvate‐driven oxidative phosphorylation in vitro

Silva

Ruiter

IJlst

et al. 1997

J of Inher Metab Disea

View full text Add to dashboard Cite

[7] Mitochondrial respiratory control and the polarographic measurement of ADP : O ratios

Cited by 1,555 publications

References 12 publications

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

The cytotoxic properties and preferential toxicity to tumour cells displayed by some 2,4-bis(benzylidene)-8-methyl-8-azabicyclo[3.2.1] octan-3-ones and 3,5-bis(benzylidene)-1-methyl-4-piperidones

Doxorubicin increases the susceptibility of brain mitochondria to Ca2+-induced permeability transition and oxidative damage

Valproate inhibits the mitochondrial pyruvate‐driven oxidative phosphorylation in vitro

Contact Info

Product

Resources

About