Stimulation of Deoxyribonucleic Acid Synthesis in the Liver Parenchymal Cells of the Intact Rat

Short, John; Zemel, Reuben; Kanta, J; Lieberman, Irving

doi:10.1038/223956a0

Cited by 45 publications

(32 citation statements)

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“…alternatively, by a proliferative response seen after subcutaneous T 3 injections in unaltered animals (2,3). T 3 also has modest hepatotrophic effects (4) that are identified in the Eck fistula screen model by the stimulation of proliferation and the prevention of hepatocyte atrophy (5).…”

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confidence: 99%

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Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Francavilla¹

1994

Hepatology

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Subcutaneous injections of hormone triiodothyronine in rats resulted in peak blood levels at 24 hr with return to baseline by 96 hr. The injections stimulated a liver regeneration response that resembled in timing and in magnitude of DNA synthesis (peak, 24 hr) that induced by 40% hepatic resection. The principal proliferation was of hepatocytes. Although there were some temporal differences from the gene expression of transforming growth factor-a, transforming growth factor-~, and c-Ha-ras that are known to follow partial hepatectomy, the overall profile of these changes was similar to those after partial resection. The effect was liver specific and could be reproduced three times with no diminution in response in the same animal with injections at 10-day intervals. No response was detected in kidney or intestine. This effect in intact animals contrasted with the minimal ability of triiodothyronine to stimulate hepatocytes in culture. However, when the culture medium was enriched with epidermal growth factor, there was a dose-related response to triiodothyronine. The totality of these experiments provides a preliminary basis for the creation with pharmacological techniques of an in vivo hyperplastic hepatic condition permissive of transfection of new genes, as an alternative to partial hepatectomy. Although triiodothyronine was the test agent used, other hepatic growth factors singly or in combination could be candidates for this purpose.

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“…For the transfection of new genes, a process that is known to be facilitated and prolonged under conditions of cellular proliferation (8), T 3 may be an acceptable substitute for partial hepatectomy. 2 PJdCTP by use of T4 kinase (end labeling system; BRL).…”

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Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Francavilla¹

1994

Hepatology

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“…The activity of 14 C-cholesterol (Bq/g of tissue or ml of blood) was determined after ethanol-acetone extraction and saponification and radioactivity was quantitated by scintillation counting (11). Newly synthesized bile acids with incorporated 14 C-cholesterol in liver were assessed after ethanol extraction, precipitation by digitonin (10) and radioactivity was quantitated by scintillation counting.…”

Section: Analysesmentioning

confidence: 99%

“…Newly synthesized bile acids with incorporated 14 C-cholesterol in liver were assessed after ethanol extraction, precipitation by digitonin (10) and radioactivity was quantitated by scintillation counting. Liver DNA synthesis was determined by incorporation of methyl 3 H-thymidine to liver DNA (11). The radioactivity of the samples was measured by liquid scintillation system on Beckman Coulter LS 6000LL (Fullerton, CA, USA).…”

Section: Analysesmentioning

confidence: 99%

Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol

Živný

Zivna

Palička

et al. 2018

Acta Med. (Hradec Kralove, Czech Repub.)

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A B ST R AC T Introduction: The aim of study was to evaluate impact of long-term dietary cholesterol overload on the cholesterol homeostasis and liver regeneration. Material and Methods: Serum lipid parameters, 14 C-cholesterol incorporation, liver DNA synthesis and protein expression was determined in partially hepatectomized (PH) rats fed with a standard (SLD) or hypercholesterolemic (CHOL) diet. Results: 29-day intake of CHOL diet before PH produced increase in serum total cholesterol, LDL lipoprotein, and triglyceride concentration. PH provoked decrease in serum total cholesterol and triglyceride concentration in both groups. PH was associated with increase in serum ALT activity more pronounced in CHOL animals. Hepatic DNA synthesis was increased after PH in both groups, but lower in CHOL. Hypercholesterolemic diet reduced the absorption of radiolabelled cholesterol in intestine and then activity in blood and liver. The 14 C-cholesterol hepatic activities tend to increase after PH in both groups. CHOL diet produced up-regulation of Acyl-CoA:cholesterol acyltransferase-2 protein expression. PH was associated with increase of LDL receptor and Acyl-CoA:cholesterol acyltransferase-2 protein expression in both dietary groups. Discussion: Liver regeneration after PH is negatively influenced by CHOL diet. The increased uptake of cholesterol in the liver after PH associated with up-regulation of LDL receptor protein expression suggests preferential use of extrahepatic cholesterol by the liver.

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“…In addition, the interaction of TGF-(3 was tested with other molecules: epidermal growth factor (EGF), which is highly stimulatory in vitro (10) but not in vivo; and triiodothymanine (T 3)' which causes feeble stimulation only in the in vivo system (1,11). The results revealed a strong, although not absolute, specificity of the TGF-a interactions with TGF-(3.…”

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Effect on the Canine Eck Fistula Liver of Intraportal Tgf–β Alone or With Hepatic Growth Factors

et al. 1992

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Transforming growth factor-p canceled the hepatocyte proliferation caused. by transforming growth factor-Of when the two substances were mixed and administered through a disconnected central portal vein branch after creation of an Eck fistula. In contrast. transforming growth factor-p had no antidotal action on the stimulatory effects of insulin or full test doses of insulinlike factor-2, hepatocyte growth factor, epidermal growth factor or triiodothymanine. A minor antidotal effect on hepatic stimulatory substance activity could be detected., but only with hepatic stimulatory substance was given in doses smaller than those known to cause maximum stimulatory response. These results suggest a highly specific pharmacological and physiological interaction between transforming growth factor-a and transforming growth factor-p in the modulation of liver growth control. (HEPATOLOGY • q92; 16: 1267-1270 The Eck fistula (portacaval shunt) in dogs is a useful tool in the identification and study of hepatic growthmodulating substances, of which some of the most potent have little or no effect on hepatocytes in culture (1). This operation is followed by tripling of hepatocyte proliferation, atrophy of hepatocytes within 4 days to about half their original volume and establishment of a new stable state after 4 days (2). Growth stimulating substances, when infused into the tied-off central portal vein after this operation, augment further the heightened proliferation of the Eck fistula liver and prevent liver atrophy after creation ofthe fistula (1, 3-7). These effects have been termed hepatotrophic. In contrast, transforming growth factor-(3 (TGF-(3), a known inhibitor of hepatocyte proliferation in vitro (8,9), has the opposite effect in that it suppresses hepatocyte proliferation after creation of the Eck fistula and further reduces the size of the atrophied hepatocytes (1). The striking TGF-(3 effect is easily overridden with insulin (1).

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Stimulation of Deoxyribonucleic Acid Synthesis in the Liver Parenchymal Cells of the Intact Rat

Cited by 45 publications

References 5 publications

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Hepatocyte proliferation and gene expression induced by triiodothyronine in vivo and in vitro

Modulation of Rat Liver Regeneration after Partial Hepatectomy by Dietary Cholesterol

Effect on the Canine Eck Fistula Liver of Intraportal Tgf–β Alone or With Hepatic Growth Factors

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