Effect of Ischemia on Known Substrates and Cofactors of the Glycolytic Pathway in Brain

Lowry, Oliver H.; Passonneau, Janet V.; Hasselberger, Francis X.; Schulz, Demoy W.

doi:10.1016/s0021-9258(18)51740-3

Cited by 2,106 publications

(68 citation statements)

References 38 publications

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“…In brain tissue, ischemia has been shown to increase glycolysis rates at least fourfold to sevenfold in different experimental groups of mice. 17 In the present experiment, the data of EPi of more than 70% were obtained exclusively when the values of the Pa02 were more than 12 mm Hg and when the initial values of the EP were more than 82 mV (Figs 3 and 6A). From the viewpoint of the PaC02, the condition of hypercapnia during hypoventilation (45 mm Hg < PaC02 < 75 mm Hg; Fig 6D) may induce a sympathicotonic state with the elevation of serum epinephrine levels.…”

Section: Discussionsupporting

confidence: 53%

“…In such hypoxemic conditions still sustaining the EP level within the positive range, the rate of energy use could be kept lower, even though ample carbohydrate reserves or adenosine triphosphate may still be available. Lowry et al 17 suggest that such a decrease of energy expenditure may represent a self-regulated protective measure geared to a more economical use of the remaining resources. In some individuals, however, the EPi in the range from 30% to 40% responds moderately to the CoBF increase (Fig 4A).…”

Section: Discussionmentioning

confidence: 99%

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Sensitivity of the Endocochlear Potential Level to Cochlear Blood Flow during Hypoventilation

Yamamoto¹,

Makimoto²

2000

Ann Otol Rhinol Laryngol

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To study the relationship between endocochlear DC potential (EP) and cochlear blood flow (CoBF) under hypoxic conditions, we recorded the EP and CoBF from the basal turn of the cochlea in 21 guinea pigs. Hypoventilation for 10 minutes was induced by reducing the respiratory rate and volume. During hypoventilation, the EP declined in most of the cases to an intermediate level of the positive range in a few minutes. At the midpoint of the 10-minute hypoventilation, angiotensin II (5 microg/kg or 1 mL/kg) was infused for 60 seconds to raise the systemic blood pressure. In this experimental manipulation of systemic blood pressure, the CoBF and EP generally rose transiently. We determined the sensitivity of the EP to a CoBF change (delta) by calculating the deltaEP/deltaCoBF. More specifically, we analyzed the relationship between the deltaEP/deltaCoBF and the EPi (EP level just before angiotensin II infusion). The deltaEP was equal to the maximum EP level after angiotensin II infusion minus the EPi. The deltaCoBF was equal to the maximum CoBF value after angiotensin II infusion minus the CoBF value just before infusion. The deltaEP/deltaCoBF increased most in the range near 70% of the EPi. That is, the deltaEP/deltaCoBF was greater and the EPi was lower in the range above 70% of the EPi. To elucidate this linear correlation in the range above 70% of the EPi, we must consider several factors. In the supplementary experiments for blood gas analysis using 11 guinea pigs, most of the data of the EPi in the range above 70% were found to be obtained under conditions of a PaO2 of more than 12 mm Hg. As to the sensitivity increase of the EP to the deltaCoBF above mentioned, we propose that among several factors in the stria vascularis during hypoxemia, the activation of glycolysis in aerobic metabolism may be involved. As another possible factor, we postulate the increase in the reactive rate of the enzymatic activities that are linked with EP production and respond to the elevated cyclic adenosine monophosphate activity induced by the sympathicotonic state due to hypercapnia.

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Section: Discussionsupporting

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Sensitivity of the Endocochlear Potential Level to Cochlear Blood Flow during Hypoventilation

Yamamoto¹,

Makimoto²

2000

Ann Otol Rhinol Laryngol

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“…During ischaemia there is rapid deterioration in the energy charge, and the tissue levels of both glycolytic substrates and intermediates are decreased (Lowry et al, 1964). Pauwels & Trouet (1984 found no predominant role of Fru-2,6-P2 at the onset of anaerobic glycolysis in various types of cultivated brain cells, concluding that it seemed not to be responsible for immediate changes in glycolytic flux.…”

Section: Discussionmentioning

confidence: 99%

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain

Ventura

Rosa

Ambrosio

et al. 1991

Biochemical Journal

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The concentration of fructose 2,6-bisphosphate in the brain remained stable during starvation and early stages of ischaemia, but decreased in diabetes or after lengthened ischaemia. 6-Phosphofructo-1-kinase activity was also decreased in diabetic and ischaemic animals, whereas 6-phosphofructo-2-kinase was not modified. The concentration of the bisphosphorylated metabolite seems to be remarkably constant under a wide variety of experimental conditions, suggesting that it plays an essential role in the basal activation of 6-phosphofructo-1-kinase. Purified 6-phosphofructo-2-kinase also showed fructose-2,6-bisphosphatase activity with an activity ratio similar to that of the purified heart isoenzyme. The brain enzyme also has a net charge similar to that of the heart isoenzyme. Its activity is not modified by sn-glycerol 3-phosphate, and it is more sensitive to citrate than the liver or muscle isoenzyme. Moreover, the enzyme from brain, similarly to that from heart and muscle, is not modified by the cyclic AMP-dependent protein kinase or protein kinase C. A near-full-length cDNA probe from liver hybridized with RNA from brain and heart. In both cases, a major band of 6.8 kb of RNA and a minor one of 4 kb of RNA were detected. All these properties support the hypothesis that brain contains a different isoenzymic form from that of liver and muscle, and it is probably related to the heart isoform.

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“…Dephosphorylation of adenine nucleotides intracellularly on excitation could contribute to output of adenosine and its derivatives in superfusates. As an indication of such dephosphorylation, we have measured the glycolysis concomitant with 14C output, as tissue glycolysis depends on the degree of phosphorylation of adenine nucleotides and on the Pi formed by their breakdown (Lowry et al, 1964).…”

mentioning

confidence: 99%

Output of [14C]adenine nucleotides and their derivatives from cerebral tissues. Tetrodotoxine-resistant and calcium ion-requiring components

Pull

McIlwain

1973

Biochemical Journal

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1. Neocortical tissues, exposed briefly to [(14)C]adenine and containing over 98% of their (14)C as adenine nucleotides, when superfused with glucose-bicarbonate salines released about 0.1% of their (14)C content/min to the superfusate. 2. Addition of unlabelled adenosine to the superfusing fluid increased the (14)C output three- to four-fold; half-maximal increase was given by about 40mum-adenosine, and reasons are adduced for considering the activity of adenosine kinase to be a major factor in conditioning the (14)C output. Adenosine similarly increased the enhanced (14)C output caused by electrical excitation of the superfused tissue; it brought about only a small increase in tissue glycolysis. 3. Output of (14)C from the [(14)C]adenine-labelled tissues was increased when Ca(2+) was omitted from the superfusing fluids, but electrical stimulation did not then liberate more (14)C. Nevertheless, such tissues still responded to electrical stimulation by increased glycolysis, and their (14)C output again became susceptible to increase by electrical stimulation when Ca(2+) was restored. 4. The six-fold increase in tissue glycolysis caused by electrical excitation was almost completely inhibited by tetrodotoxin at 0.1mum and above, but this was associated with about 50% inhibition only in the output of (14)C from tissues preincubated with [(14)C]adenine. The (14)C-labelled compounds of which output was most inhibited by tetrodotoxin were adenosine, inosine and hypoxanthine whereas output in a nucleotide fraction was little affected.

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Effect of Ischemia on Known Substrates and Cofactors of the Glycolytic Pathway in Brain

Cited by 2,106 publications

References 38 publications

Sensitivity of the Endocochlear Potential Level to Cochlear Blood Flow during Hypoventilation

Sensitivity of the Endocochlear Potential Level to Cochlear Blood Flow during Hypoventilation

6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in rat brain

Output of [14C]adenine nucleotides and their derivatives from cerebral tissues. Tetrodotoxine-resistant and calcium ion-requiring components

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