A histochemical study of succinic dehydrogenase activity in rat liver cancerogenesis induced by 3-methyl-4-dimethylaminoazobenzene

Résumé L'auteur a étudié histochimiquement l'activité de la succine déhydrogénase lors de la cancérogénèse expérimentale du foie des rats induite par le 3'-méthyl-4-diméthylaminoazobenzène. On a observé une augmentation de l'activité enzymatique dans les stades précancéreux (cholangiofibrose et hypertrophie parenchymateuse) suivie d'une diminution et disparition de cette activité dans les tumeurs développés.     

Influence of 2-methyl-2-(p-1,2,3,4-tetrahydro-1-naphthylphenoxy)propionic acid on the oxidation of cholesterol by rat liver mitochondria

Zusammenfassung Es wird gezeigt, dass bei männlichen Wistar-Ratten im 3-Wochen-Diätexperiment mit Zusatz von 0,3% 2-Methyl-2-(p-1,2,3,4-Tetrahydro-1-naphthylphenoxy)-Propionsäure (Su-13437) die Oxydation von 26-¹⁴C-Cholesterin zu¹⁴CO₂ durch Lebermitochondrien (bezogen auf mg/N) ähnlich wie bei den Kontrollen war. Bei den Versuchstieren war jedoch bei Abwesenheit von Cytosol im System die Oxydation durch Lebermitochondrien erhöht.

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Acknowledgment. This work was supported, in part, by a grant No. HE-03299 and a Research Career Award No. 4-K6-HE-0734 from the National Heart Institute, N.I.H. We are indebted to Dr. W. I.Taylor, CIBA Pharmaceutical Co., Summit, N.J., for the generous gift of Su-13,437.     

Protein synthesis stimulation in rat liver by chloroquine

Riassunto L'inoculazione endoperitoneale di Clorochina, a dosi comprese tra 15 e 45 mg/kg di peso corporeo determina una stimolazione precoce delle sintesi proteiche nel fegato di ratto. Questa azione non é correlata ad un aumento della sintesi di RNA, né appare conseguente ad una stimolazione corticosurrenalica. L'effetto osservato é brevemente discusso sulla base delle note interazioni tra lisosomi e Clorochina.     

Inhibition of DNA synthesis in regenerating rat liver by hydrocortisone

Résumé Dans le foie du rat en voie de régénération, la biosynthèse de DNA est inhibée au maximum par le hydrocortisone 17–19 h après l'opération. C'est pourquoi le foie en régénération est le plus sensible au hydrocortisone s'il est injecté pendant la période de la synthèse maximale de DNA.     

Pantothenic acid distribution and protein synthesis in the particulate fractions of rat liver

Zusammenfassung Ratten wurden während 10 Wochen mit durch Pantothensäure angereicherte Nahrung oder mit Pantothensäure-Mangeldiät gefüttert. Im Anschluss daran wurden die durch Differentialzentrifugation gewonnenen Fraktionen von Leberhomogenat auf ihren Protein- und Panthothensäuregehalt untersucht. Die Resultate deuten darauf hin, dass Panthothensäure die Synthese von Leberproteinen, insbesondere in der Überstands-Fraktion, stimuliert.

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Acknowledgement. Authors thank Dr. (Mrs.)A. Venkataraman and Dr.N. K. Dutta, Director of this Institute, for their encouragement and interest, and they are also grateful to Dr.M. J. Modak for his kind help.     

Oxidation of cholesterol by rat liver mitochondria: Influence of deuterium oxide

Résumé L'oxydation du cholestérol-26-¹⁴C et de l'octanoate de sodium-1-¹⁴C par une préparation de mitochondries de foie de rat a été effectuée en milieu aqueux à un pH de 8,5 et dans l'eau lourde (D₂O) à un pH de 8,1 et 8,5. La présence d'eau lourde a inhibé l'oxydation des deux substrats. L'oxydation du cholestérol dans l'eau lourde à un pH de 8,5 a été réduite de 60% à 70% de la valeur normale et de plus de 90 % dans l'eau lourde à un pH de 8,1. Aux deux valeurs de pH, l'oxydation de l'octanoate a été réduite de 50% à 70%.     

Enzymatic synthesis of trisialoganglioside by particulate fractions of rat liver

Summary Rat liver contains a particulate (membrane-bound) glycosyl transferase, concentrated in Golgi apparatus fractions, which catalyzes the synthesis of a trisialoganglioside from the ganglioside precursor disialohematoside (G_D3). Sialic acid was not incorporated into exogenous G_D1a from CMP-N-acetylneuraminic acid suggesting that G_D1a is an endproduct of the monosialoganglioside pathway. Thus, the disialoganglioside pathway may be a primary source of trisialoganglioside and higher ganglioside homologs in adult rat liver.     

Albumin synthesis in regenerating rat liver cells

Riassunto Gli autori hanno studiatoin vitro il problema della sintesi dell'albumina in sezioni di fegato normale e rigenerante di ratto. La quantità di albumina prodotta durante l'incubazione non presenta notevoli variazioni nelle due situazioni studiate. Al contrario l'incorporazione di glicina marcata nella albumina del fegato rigenerante risulta nettamente aumentata rispetto a quella del fegato normale. Tale comportamento viene interpretato come espressione di un ricambio albuminico più elevato nel fegato rigenerante che nel normale.

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This investigation was aided by a grant from C.N.R., Roma, and was made during a tenure by one of us (G. G.) of a Scholarship from C.N.R., Roma.     

Effect of prostaglandin E1 on cholesterol biosynthesis in rat liver

Riassunto La prostaglandina E₁ (PGE₁) ha un duplice effetto sulla sintesi epatica del colesterolo: a basse concentrazioni determina un incremento della incorporazione di acetato in colesterolo, mentre a concentrazini superiori a 50 nmoli essa determina una riduzione di questo paramentro.     

Digoxin and ouabain increase the synthesis of cholesterol in human liver cells

Digoxin and ouabain are steroid drugs that inhibit the Na⁺/K⁺-ATPase, and are widely used in the treatment of heart diseases. They may also have additional effects, such as on metabolism of steroid hormones, although until now no evidence has been provided about the effects of these cardioactive glycosides on the synthesis of cholesterol. Here we report that digoxin and ouabain increased the synthesis of cholesterol in human liver HepG2 cells, enhancing the activity and the expression of the 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the cholesterol synthesis. This effect was mediated by the binding of the sterol regulatory element binding protein-2 (SREBP-2) to the HMGCR promoter, and was lost in cells silenced for SREBP-2 or loaded with increasing amounts of cholesterol. Digoxin and ouabain competed with cholesterol for binding to the SREBP-cleavage-activating protein, and are critical regulators of cholesterol synthesis in human liver cells. Received 10 January 2009; received after revision 11 February 2009; accepted 6 March 2009     

Effect of aflatoxin B1 on the incorporation of14C-acetate into cholesterol by rat liver

Résumé L'administration d'aflatoxine B₁ (2 et 5 mg/kg, i.p., 24 h avant le sacrifice) a résulté en un abaissement de 80% de l'incorporation du l-¹⁴C-acétate en cholestérol par des coupes de tissu de foie. Le même traitement n'a pas altéré l'activité des drug metabolizing enzymes au niveau des microsomes du foie.     

Inhibition of rat liver glutamine synthetase by phosphonic analogues of glutamic acid

Summary Analogues of glutamic acid, -methylglutamic acid and glutamine in which the -or -COOH groups are replaced by PO₃H₂ or P(O)(OH₃)OH functions competitively inhibit rat liver glutamine synthetase. The K₁ values are comparable to or lower than K_M for L-glutamate.This study was supported by grant R.1.9.