The Phosphorylation of Proteins in Hippocampal Slices: Effects of Noradrenaline and of Pretreatment with Kainic Acid

Hofstein, Raphael; Segal, Menachem

doi:10.1111/j.1471-4159.1982.tb03969.x

Cited by 3 publications

(2 citation statements)

References 29 publications

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“…Brain PDH kinase and phosphatase have similar properties to those found in peripheral tissue (Booth and Clark, 1978; Sheu et aI., 1983 Sheu et aI., , 1984, but the regulation of brain PDHC is still not fully un derstood (Kauppinen and Nicholls, 1986;Lai and Sheu, 1985). Apart from regulation of PDHC by feedback inhibition by metabolites of intermediary metabolism, external influences such as neurotrans mitters and neuromodulators may change the activ ity of the enzyme via second messenger systems (Hershkowitz, 1978;Sieghart, 1981;Hofstein and …”

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confidence: 78%

Pyruvate Dehydrogenase Activity in the Rat Cerebral Cortex following Cerebral Ischemia

Cardell

Koide

Wieloch

1989

J Cereb Blood Flow Metab

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Summary: The effect of cerebral ischemia on the activity of pyruvate dehydrogenase (PDH) enzyme complex (PDHC) was investigated in homogenates of frozen rat cerebral cortex following 15 min of bilateral common ca rotid occlusion ischemia and following 15 min, 60 min, and 6 h of recirculation after 15 min of ischemia. In frozen cortical tissue from the same animals, the levels of labile phosphate compounds, glucose, glycogen, lactate, and pyruvate were determined. In cortex from control ani mals, the rate of [l_14C]pyruvate decarboxylation was 9.6 ± 0.5 nmol CO2/(min-mg protein) or 40% of the total PDHC activity. This fraction increased to 89% at the end of 15 min of ischemia. At 15 min of recirculation following 15 min of ischemia, the PDHC activity decreased to 50% of control levels and was depressed for up to 6 h post ischemia. This decrease in activity was not due to a de crease in total PDHC activity. Apart from a reduction in ATP levels, the acute changes in the levels of energy metabolites were essentially normalized at 6 h of recov ery. Dichloroacetate (DCA), an inhibitor of PDH kinase, given to rats at 250 mg/kg i.p. four times over 2 h, signifThe pyruvate dehydrogenase (POH) complex (POHC) is a mitochondrial multienzyme complex composed of three enzyme activities, participating in the decarboxylation of pyruvate and formation of acetyl-CoA (Reed, 1981). It is a central enzyme in the metabolism of glucose and in acetylcholine syn thesis (Tucek and Cheng, 1974; Gibson et aI. , 1975), but has also been proposed to be important in neu ronal plasticity and accommodative processes via effects on the cellular calcium ion homeostasis (Morgan and Routtenberg, 1981; Browning et aI. , 1981;Baudry and Lynch, 1985 350icantly decreased blood glucose levels from 7.4 ± 0.6 to 5.1 ± 0.3 mmoUL and fully activated PDHC. In animals in which the plasma glucose level was maintained at control levels of 8. 3 ± 0.5 IJ-mol/g by intravenous infusion of glu cose, the active portion of PDHC increased to 95 ± 4%. In contrast, the depressed PDHC activity at 15 min fol lowing ischemia was not affected by the DCA treatment. In both DCA + glucose-treated control and recovery groups, the pyruvate levels decreased by 50%. No signif icant difference in the lactate levels was seen. We con clude that the depressed postischemic PDHC activity is not due to loss of enzyme protein nor to an increased PDH kinase activity, but is probably due to a decreased activity of PDH phosphatase. This could in turn be sec ondary to a change in the cellular levels of PDH phos phatase regulators, most probably a decreased intramito chondrial concentration of calcium. The postischemic de crease in PDH activity may be related to the postischemic metabolic depression. Key Words: Brain-Dichloro acetate-Ischemia-Pyruvate dehydrogenase-Rat.Phosphorylation-dephosphorylation of the a-subunit protein of POHC regulates the enzyme activity via reactions catalyzed by a PDH phos phatase that activates, and a PDH kinase that inac tivates, the enzyme (for review see Reed,...

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confidence: 78%

Pyruvate Dehydrogenase Activity in the Rat Cerebral Cortex following Cerebral Ischemia

Cardell

Koide

Wieloch

1989

J Cereb Blood Flow Metab

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“…Furthermore, changes in the activation state of PDHC (i.e., phosphorylation state of the 41,000 dalton peptide) have been reported as results of repetitive stimulation (Browning et al, 1978(Browning et al, , 1980, entorhinal cortex lesions (Baudry et al, 1982), and training (Morgan and Routtenberg, 1981). Glutamate (Sieghart,198l), calcium ion (Hershkowitz, 1978), and noradrenaline (Hofstein and Segal, 1982) also change the phosphorylation state of a peptide of similar size, which was suggested to be the a-peptide of pyruvate dehydrogenase (Sieghart, 1981 ;Magilan et al, 1981).…”

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confidence: 99%

Properties and Regional Distribution of Pyruvate Dehydrogenase Kinase in Rat Brain

Sheu

Lai

Blass

1984

Journal of Neurochemistry

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A method is described to measure directly in rat brain the activity of pyruvate dehydrogenase kinase (PDHa kinase; EC 2.7.1.99), which catalyzes the inactivation of pyruvate dehydrogenase complex (PDHC, EC 1.2.4.1, EC 2.3.1.12, and EC 1.6.4.3). The activity showed the expected dependence on added ATP and divalent cation, and the expected inhibition by dichloroacetate, pyruvate, and thiamin pyrophosphate. These results, and the properties of pyruvate dehydrogenase phosphate phosphatase (EC 3.1.3.43), indicate that the mechanisms of control of phosphorylation of PDHC seem qualitatively similar in brain to those in other tissues. Regionally, PDHa kinase is more active in cerebral cortex and hippocampus, and less active in hypothalamus, pons and medulla, and olfactory bulbs. Indeed, the PDHa kinase activity in olfactory bulbs is uniquely low, and is more sensitive to inhibition by pyruvate and dichloroacetate than that in the cerebral cortex. Thus, there are significant quantitative differences in the enzymatic apparatus for controlling PDHC activity in different parts of the brain.

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Protein Phosphorylation

Ehrlich¹

1984

Handbook of Neurochemistry

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The Phosphorylation of Proteins in Hippocampal Slices: Effects of Noradrenaline and of Pretreatment with Kainic Acid

Cited by 3 publications

References 29 publications

Pyruvate Dehydrogenase Activity in the Rat Cerebral Cortex following Cerebral Ischemia

Pyruvate Dehydrogenase Activity in the Rat Cerebral Cortex following Cerebral Ischemia

Properties and Regional Distribution of Pyruvate Dehydrogenase Kinase in Rat Brain

Protein Phosphorylation

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