Phosphocreatine Synthesis by Isolated Rat Skeletal Muscle Mitochondria Is Not Dependent upon External ADP: A 31P NMR Study

Kernec, Florence; Tallec, Nathalie Le; Nadal, Lydie; Bégué, Jean-Marc; Rumeur, Élisabeth Le

doi:10.1006/bbrc.1996.1257

Cited by 18 publications

(12 citation statements)

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Section: Discussionmentioning

confidence: 99%

“…We found that pretreatment with creatine completely abolished all inhibitory effects induced by QA injection on striatum bioenergetics. This may be due to fact that creatine is an excellent stimulant of mitochondrial respiration, resulting in the generation of phosphocreatine and, secondarily, ATP (Kernec et al 1996;O'Gorman et al 1996). Furthermore, the rise in the phosphocreatine/ATP ratio may serve to power ion pumps, especially the energetically demanding sarcoplasmic-endoplasmic reticulum Ca 2+ -ATPase pump (Wallimann and Hemmer 1994), whose activities are required to maintain ion homeostasis, excitability, and Ca 2+ signaling.…”

Section: Discussionmentioning

confidence: 99%

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Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats

Ribeiro

Grando

Dutra-Filho

et al. 2006

Journal of Neurochemistry

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In the present study we investigated the effect of intrastriatal administration of 150 nmol quinolinic acid to young rats on critical enzyme activities of energy production and transfer, as well as on 14 CO 2 production from [1-14 C]acetate at distinct periods after quinolinic acid injection. We observed that quinolinic acid injection significantly inhibited complexes II (50%), III (46%) and II-III (35%), as well as creatine kinase (27%), but not the activities of complexes I and IV and citrate synthase in striatum prepared 12 h after treatment. In contrast, no alterations of these enzyme activities were observed 3 or 6 h after quinolinic acid administration. 14 CO 2 production from [1-14 C]acetate was also significantly inhibited (27%) by quinolinic acid in rat striatum prepared 12 h after injection. However, no alterations of these activities were observed in striatum homogenates incubated in the presence of 100 lM quinolinic acid . Pretreatment with the NMDA receptor antagonist MK-801 and with creatine totally prevented all inhibitory effects elicited by quinolinic acid administration. In addition, a-tocopherol plus ascorbate and the nitric oxide synthase inhibitor L-NAME completely abolished the inhibitions provoked by quinolinic acid on creatine kinase and complex III. Furthermore, pyruvate pretreatment totally blocked the inhibitory effects of quinolinic acid injection on complex II activity and partially prevented quinolinic acidinduced creatine kinase inhibition. These observations strongly indicate that oxidative phosphorylation, the citric acid cycle and cellular energy transfer are compromised by high concentrations of quinolinic acid in the striatum of young rats and that these inhibitory effects were probably mediated by NMDA stimulation.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats

Ribeiro

Grando

Dutra-Filho

et al. 2006

Journal of Neurochemistry

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“…The PCr is exported to the cytosol, whereas the produced ADP is pumped back to the mitochondrial matrix via ANT, thus stimulating oxidative phosphorylation (37)(38)(39). In fact, Cr is an excellent stimulant for mitochondrial respiration during PCr generation (31,40,41). Besides its role on energy metabolism it has recently been demonstrated that activation of mt-CK inhibits the mitochondrial permeability transition (MPT), a process that is involved in apoptosis (42).…”

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confidence: 99%

Mitochondrial Creatine Kinase Activity Prevents Reactive Oxygen Species Generation

Meyer

Machado

Santiago

et al. 2006

Journal of Biological Chemistry

175

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As recently demonstrated by our group (da-Silva, W. S., Gómez-Puyou, A., Gómez-Puyou, M. T., Moreno-Sanchez, R., De Felice, F. G., de Meis, L., Oliveira, M. F., and Galina, A. (2004) J. Biol. Chem. 279, 39846 -39855) mitochondrial hexokinase activity (mt-HK) plays a preventive antioxidant role because of steady-state ADP re-cycling through the inner mitochondrial membrane in rat brain. In the present work we show that ADP re-cycling accomplished by the mitochondrial creatine kinase (mt-CK) regulates reactive oxygen species (ROS) generation, particularly in high glucose concentrations. Activation of mt-CK by creatine (Cr) and ATP or ADP, induced a state 3-like respiration in isolated brain mitochondria and prevention of H 2 O 2 production obeyed the steady-state kinetics of the enzyme to phosphorylate Cr. The extension of the preventive antioxidant role of mt-CK depended on the phosphocreatine (PCr)/Cr ratio. Rat liver mitochondria, which lack mt-CK activity, only reduced state 4-induced H 2 O 2 generation when 1 order of magnitude more exogenous CK activity was added to the medium. Simulation of hyperglycemic conditions, by the inclusion of glucose 6-phosphate in mitochondria performing 2-deoxyglucose phosphorylation via mt-HK, induced H 2 O 2 production in a Crsensitive manner. Simulation of hyperglycemia in embryonic rat brain cortical neurons increased both ⌬⌿ m and ROS production and both parameters were decreased by the previous inclusion of Cr. Taken together, the results presented here indicate that mitochondrial kinase activity performed a key role as a preventive antioxidant against oxidative stress, reducing mitochondrial ROS generation through an ADP-recycling mechanism.Mitochondrial electron transport chain is the major and continuous source of cellular reactive oxygen species (ROS), 5 which are involved in several conditions, such as apoptosis, ischemia-reperfusion injury, neurodegenerative diseases, and toxicity induced by hyperglycemia (1-5). Electron leakage at the complexes I (6, 7) and III (6, 8 -10) are the main sites for the monoelectronic reduction of oxygen, which results in superoxide (O 2 . ) radical production in the respiratory chain. The rate of mitochondrial ROS production is highly dependent on the mitochondrial membrane potential (⌬⌿ m ) (9, 11) and evidence supporting these observations have long demonstrated (9) that pharmacological uncoupling of oxidative phosphorylation caused a drastic reduction in mitochondrial H 2 O 2 formation. Similarly, activation of oxidative phosphorylation by ADP can also reduce the ⌬ m and ROS formation through activation of F 1 F 0 -ATP synthase complex by using the energy of the ⌬⌿ m to drive ATP synthesis (9, 11). On the other hand, when mitochondrial ADP levels drop, the respiratory rate is reduced, increasing the ⌬⌿ m levels, which ultimately leads to ROS generation. There is a clear link between the increased levels of oxidative stress markers and several neuropathies such as amyotrophic lateral sclerosis, Parkinson and Alzheimer disease and h...

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“…27 Oral creatine supplementation increases mitochondrial respiration and PCr synthesis. 1,28 In vitro, incubation of guinea pig hippocampal slices preparations in creatine results in a signi cant prolongation of synaptic transmission 29 and a dose-dependant inhibition of anoxic damage in the rat hippocampal slice. 30 In vivo, creatine will protect against 3-NP induced striatal pathology.…”

Section: Creatinementioning

confidence: 99%

Creatine and coenzyme Q10 in the treatment of ALS

Strong¹,

Pattee²

2000

Amyotrophic Lateral Sclerosis and Other Motor Neuron Disorders

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Phosphocreatine Synthesis by Isolated Rat Skeletal Muscle Mitochondria Is Not Dependent upon External ADP: A 31P NMR Study

Cited by 18 publications

References 0 publications

Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats

Evidence that quinolinic acid severely impairs energy metabolism through activation of NMDA receptors in striatum from developing rats

Mitochondrial Creatine Kinase Activity Prevents Reactive Oxygen Species Generation

Creatine and coenzyme Q10 in the treatment of ALS

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