Energy-producing machinery in vasogenic brain edema
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This paper investigates the functioning of mitochondrial energy-producing machinery in cold-induced edema and the level of energy charge available within the cell for cation transport.
Direct measurements of mitochondrial ATP production in vasogenic brain edema are carried out by testing different metabolic pathways.
In our model (freezing lesion edema), substrate level phosphorylation is not affected by the cold injury. However, when the respiratory substrates are glutamate + malate or pyruvate + malate, the inhibition of ATP production in mitochondria isolated from edematous cells reflects the decrease of oligomycin-sensitive ATPase. The larger inhibition of the succinate dehydrogenase activity seems to affect only the phosphorylations coupled to succinate oxidation.
Alternative transmembranal metabolic pathways (i.e., aspartate-malate shuttle, pyruvate cycle) bypassing the step might be operating in these edematous cells and play an important energetic role. Indeed, under in vivo conditions, the energy charge remains normal and the ATP/ADP ratio higher than normal during edema expansion.
These results are consistent with a large decrease in Na+, K+-ATPase function (Rigoulet et al., 1979), which normally uses an important part of available ATP.
We conclude that the development of intracellular edema is caused by the breakdown of Na+, K+-ATPase and not by a shortage of high energy compounds.
Index EntriesEnergy producing machinery, in brain edema brain edema, energy producing machinery in edema, energy producing machinery in brain vasogenic brain edema, energy producing machinery in
carbonyl cyanide m-chlorophenylhydrazone
regional cerebral blood flow
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- Borst P. (1963) Hydrogen transport and transport. inFunctionnelle und Morphologische Organization der Zelle (Karlson P., ed.), pp. 137–162, Springer-Verlag, Berlin.Google Scholar
- Demopoulos H. B., Flamm E. S., Seligman M. L., Mitamura J. A., and Ransohoff J. (1979) Membrane perturbations in central nervous system injury: theoretical basis for free radical damage and a review of the experimental data. InNeural Trauma (Popp A.J., Bourke R.S., Nelson L.R., and Kimelberg, H.K., eds.), pp. 63–78. Raven Press, New-York.Google Scholar
- Golberg N. D., Passonneau J. V., and Lowry O. H. (1966) Effects of changes in brain metabolism on the levels of citric acid cycle intermediates.J. Biol. Chem. 241, 3997–4003.Google Scholar
- Klatzo I., Wisniewski H., and Smith D. E. (1965) Observations on penetration of serum proteins into the central nervous system. InProgress in Brain Research, Vol. 15, Biology of Neuroglia (De Robertis E. D. P. and Carrea R., eds.) pp. 73–88, Elsevier, Amsterdam.Google Scholar
- Klatzo I., Chui E., Feijiwara K., and Spatz M. (1980) Resolution of vasogenic brain edema. InAdvances in Neurology, Vol. 28, Brain Edema (Cervos-Navarro J. and Ferszt R., eds.) pp. 359–373, Raven Press, New York.Google Scholar
- Marmarou A., Takagi H., and Shulman K. (1980) Biomechanics of brain edema and effects on local cerebral blood flow. in:Advances in Neurology, Vol. 28, Brain Edema (Cervos-Navarro J. and Ferszt R., eds.), pp. 345–358, Raven Press, New York.Google Scholar
- Meijer A. J. and Van Dam K. (1974) The metabolic significance of anion transport in mitochondria.Biochim. Biophys. Acta 364, 213–244.Google Scholar
- Nicholls D. G. and Bernson S. M. (1977) Interrelationships between proton electrochemical gradient, adeninenucleotide phosphorylation potential and respiration, during substrate level and oxidative phosphorylation by mitochondria from brown adipose tissue of cold-adapted guinea-pigs.Eur. J. Biochem. 75, 601–612.PubMedCrossRefGoogle Scholar
- Ozawa K., Itada N., Kuno S., Seta K., Handa H., and Araki C. (1966) Biochemical studies on brain swelling. I. Changes in respiratory control, 2,4-dinitrophenol induced ATPase activity and phosphorylation. Correlation between brain swelling and mitochondrial function.Folia Psychiatr. Neurol. Japonica 20, 57–72.Google Scholar
- Robinson B. H., Williams G. R., Halperin M. L., and Leznoff C. C. (1971) The sensitivity of the exchange reactions of tricarboxylate, 2-oxoglutarate and dicarboxylate transporting systems of rat liver mitochondria to inhibition by 2-pentylmalonate,p-iodobenzylmalonate and benzene 1,2,3-tricarboxylate.Eur. J. Biochem. 20, 65–71.PubMedCrossRefGoogle Scholar
- Singer T. P., Rocca E. and Kearney E. B. (1966) Fumarate reductase, succinate and NADH dehydrogenase of yeast: properties and biosynthesis. InFlavins and Flavoproteins (Slater B. C., ed.), pp. 391–426, Elsevier, Amsterdam, London, New York.Google Scholar
- Whittam R. (1962) The dependence of the respiration of brain cortex on active cation transport.Biochemistry 82, 205–212.Google Scholar