Abstract
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.
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Abbreviations
- AdN:
-
adenylic nucleotides
- CCCP:
-
carbonyl cyanide m-chlorophenylhydrazone
- 2,6-DCIP:
-
2,6-dichlorophenol indophenol
- Pi :
-
inorganic phosphate
- PMS:
-
phenazine methosulfate
- iCBF:
-
regional cerebral blood flow
- TCA:
-
trichloroacetic acid
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Rigoulet, M., Averet, N. & Cohadon, F. Energy-producing machinery in vasogenic brain edema. Neurochemical Pathology 1, 43–57 (1983). https://doi.org/10.1007/BF02834131
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DOI: https://doi.org/10.1007/BF02834131