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Titolo:
Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenaseof rat brain in vitro: relevance to sporadic Alzheimer's disease?
Autore:
Yun, SW; Hoyer, S;
Indirizzi:
Univ Heidelberg, Dept Pathochem & Gen Neurochem, D-69120 Heidelberg, Germany Univ Heidelberg Heidelberg Germany D-69120 , D-69120 Heidelberg, Germany
Titolo Testata:
JOURNAL OF NEURAL TRANSMISSION
fascicolo: 3, volume: 107, anno: 2000,
pagine: 355 - 368
SICI:
0300-9564(2000)107:3<355:EOLLOG>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
CEREBRAL GLUCOSE-METABOLISM; ACTIVE-SITE; YEAST HEXOKINASE; LATE-ONSET; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE; NEUROFIBRILLARY CHANGES; ENERGY-METABOLISM; EXPOSURE; INACTIVATION; DEMENTIA;
Keywords:
lead; brain glucose metabolism; hexokinase; pyruvate dehydrogenase; Alzheimer's disease;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
76
Recensione:
Indirizzi per estratti:
Indirizzo: Hoyer, S Univ Heidelberg, Dept Pathochem & Gen Neurochem, Neuenheimer Feld220-221,D-69120 Heidelberg, Germany Univ Heidelberg Neuenheimer Feld 220-221 Heidelberg Germany D-69120
Citazione:
S.W. Yun e S. Hoyer, "Effects of low-level lead on glycolytic enzymes and pyruvate dehydrogenaseof rat brain in vitro: relevance to sporadic Alzheimer's disease?", J NEURAL TR, 107(3), 2000, pp. 355-368

Abstract

Lead is known to be a potent inhibitor of many enzymes working in the brain, thus possibly inducing functional problems in the brain under pathophysiological conditions. Among such enzymes are those involved in glucose metabolism and energy production. We investigated the inhibitory effects of low-level lead on brain hexokinase (HK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH, pyruvate kinase (PK) and pyruvate dehydrogenase complex (PDHc) with rat brain homogenate. PDHc was distinctively inhibited when low-dose lead acetate was added last of all (IC50 = 5 mu M) to the reaction mixture. The other enzymes were completely resistant to 5 mu M of lead acetate. When the homogenate was preincubated with lead acetate HK was dramatically inhibited by low-level lead acetate (1-5 mu M), in a manner dependent on both preincubation time and lead concentration. However, the inhibitory effect wasabolished by coincubation with its substrates, glucose or ATP. The resultssuggest that exposure to low levels of lead may increase the risk of cerebral hypometabolism caused by direct inhibition of specific glucose-utilizing enzymes. In this context, lead might be regarded as a risk factor in the abnormal glucose metabolism seen in some kinds of neurodegenerative disorders such as sporadic Alzheimer's disease.

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Documento generato il 24/01/20 alle ore 12:14:40