Effect of thyroparathyroidectomy on the activities of thymidylate synthetase and thymidine kinase during liver regeneration after partial hepatectomy

1987 ◽  
Vol 72 (4) ◽  
pp. 455-461 ◽  
Author(s):  
Rieko Nakata ◽  
Ikuyo Tsukamoto ◽  
Masamitsu Miyoshi ◽  
Shosuke Kojo
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Time Dependence ◽  
Thymidine Kinase ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Thymidylate Synthetase ◽  
High Dose ◽  
Regenerating Liver ◽  
Relative Contribution

1. Thyroparathyroidectomy (TPTX) carried out at 72 h before partial hepatectomy (PH) reduced the induction of hepatic thymidylate synthetase (TS) and thymidine kinase (TK), which are rate-determining enzymes in DNA synthesis, at 24 h after PH. 2. When TPTX was carried out at 24 h before PH, TK activity at 24 h after PH was not reduced at all, yet TS activity was reduced significantly. Thus the effect of TPTX differed in time dependence between TS and TK. 3. The depression of TK activity in rats which were subjected to TPTX at 72 h before PH, was recovered by Ca2+ supplementation. This result demonstrated that the rise of TK activity in regenerating liver is regulated by plasma Ca2+. 4. Since a high dose of tri-iodothyronine (T3) was required to cause elevation of the activities of these enzymes and DNA content in 24 h-regenerating liver of TPTX rats, the relative contribution of T3 to liver regeneration may be small.

DEOXYCYTIDYLATE DEAMINASE LEVELS IN REGENERATING RAT LIVER

1961 ◽  
Vol 39 (6) ◽  
pp. 1043-1054 ◽  
Author(s):  
D. K. Myers ◽  
C. Anne Hemphill ◽  
Constance M. Townsend
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Deoxyribonucleic Acid ◽  
Regenerating Liver ◽  
Regenerating Rat Liver ◽  
High Level ◽  
Early Regeneration

Deoxycytidylate deaminase activity and net synthesis of deoxyribonucleic acid (DNA) in vivo were found to increase at approximately the same time during the early stages of liver regeneration. However, deaminase activity in the regenerating liver remained at a high level for 1 day after DNA synthesis had slowed down again during the later stages of regeneration. The increase in deaminase activity was restricted as a result of exposure to 600 r X radiation during early regeneration, but this effect only became evident 11–16 hours after the irradiation. Irradiation on the second day after partial hepatectomy, when deaminase levels in control regenerating livers were relatively constant, failed to affect the deaminase activity immediately but did produce a 40–50% decrease in activity 11–16 hours later. Other antimitotic agents, e.g., colchicine, had little effect on deaminase activity.

Influence of epidermal growth factor on liver regeneration after partial hepatectomy in mice

1991 ◽  
Vol 128 (3) ◽  
pp. 425-431 ◽  
Author(s):  
S. Noguchi ◽  
Y. Ohba ◽  
T. Oka
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Sharp Peak ◽  
Submandibular Glands ◽  
Total Liver ◽  
Epidermal Growth

ABSTRACT The role of epidermal growth factor (EGF) in liver regeneration was studied in mice after partial hepatectomy. Two weeks before partial hepatectomy, mice were sham-operated (control) or sialoadenectomized (removal of submandibular glands) to reduce plasma EGF levels. Sialoadenectomized mice showed low plasma EGF levels (29·7 ±6·6 pmol/l; mean ± s.e.m.) compared with controls (66·0±8·3 pmol/l). After partial hepatectomy, sialoadenectomized mice were treated with or without a daily s.c. injection of 5 μg EGF and the rate of DNA synthesis in the regenerating liver was monitored by [125I]iododeoxyuridine uptake. Control mice showed a sharp peak of DNA synthesis at 48 h after partial hepatectomy while sialoadenectomized mice showed a delayed and broad peak at 84 h. Treatment of sialoadenectomized mice with EGF (5 μg/mouse per day) completely restored the pattern of DNA synthesis so that a sharp peak appeared at 48 h. The total liver DNA content of the control mice (79·1±2·5% of the preoperative level; mean ± s.e.m.) was significantly (P < 0·01) higher than that of the sialoadenectomized mice (65·2±3·0%) 3 days after partial hepatectomy, but this difference disappeared on day 7 when liver regeneration was almost completed in both groups. Treatment of sialoadenectomized mice with EGF increased total liver DNA content (78·2±2·9%) to that of control mice on day 3 after partial hepatectomy. In addition, normal mice showed a rapid increase in plasma EGF levels at 1–8 h after partial hepatectomy, whereas sialoadenectomized mice showed low plasma EGF levels throughout the course of the experiment. These results suggest that EGF derived from the submandibular glands plays a role in promoting the early stage of liver regeneration. Journal of Endocrinology (1991) 128, 425–431

α-Adrenergic regulation of the activity of thymidylate synthetase and thymidine kinase during liver regeneration after partial hepatectomy

1985 ◽  
Vol 114 (3) ◽  
pp. 355-360 ◽  
Author(s):  
Rieko Nakata ◽  
Ikuyo Tsukamoto ◽  
Mariko Nanme ◽  
Sawami Makino ◽  
Masamitsu Miyoshi ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Thymidine Kinase ◽  
Partial Hepatectomy ◽  
Thymidylate Synthetase ◽  
Adrenergic Regulation

Effects of methotrexate on rat liver regeneration after partial hepatectomy

1992 ◽  
Vol 82 (2) ◽  
pp. 181-184 ◽  
Author(s):  
Ikuyo Tsukamoto ◽  
Shosuke Kojo
Keyword(s):  
Liver Regeneration ◽  
Thymidine Kinase ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Liver Weight ◽  
Regenerating Liver ◽  
Dna And Rna ◽  
Immunoblotting Assay

1. Methotrexate was administered immediately after partial (70%) hepatectomy, resulting in complete inhibition of dihydrofolate reductase in 24 h-regenerating liver. 2. At 48 h and 72 h after partial hepatectomy, thymidylate synthase activity was increased, whereas thymidine kinase was inhibited, by the injection of methotrexate. The DNA and RNA contents and the liver weight were also reduced in methotrexate-treated rats. 3. The immunoblotting assay showed that methotrexate stimulated the synthesis of thymidylate synthase protein in 48 h-regenerating liver. At the same time, thymidylate synthase activity was directly inhibited by methotrexate. The mechanisms of inhibition of these enzymes by methotrexate appeared to be different.

Vasopressin modulates liver regeneration in the Brattleboro rat

1983 ◽  
Vol 245 (2) ◽  
pp. G321-G324 ◽  
Author(s):  
W. E. Russell ◽  
N. L. Bucher
Keyword(s):  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Dna Content ◽  
Brattleboro Rat

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin deficiency (Brattleboro strain), both in rate of DNA synthesis and in return of liver DNA content to normal. Vasopressin treatment at physiological doses ameliorates the defect and thus appears to be an important modulator of liver regeneration in response to partial hepatectomy in the rat.

Restriction of gut-derived endotoxin impairs DNA synthesis for liver regeneration

1985 ◽  
Vol 249 (5) ◽  
pp. R563-R569 ◽  
Author(s):  
R. P. Cornell
Keyword(s):  
Liver Resection ◽  
Dna Synthesis ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Lipid A ◽  
Subcutaneous Administration ◽  
Endotoxin Tolerance ◽  
Polymyxin B ◽  
Gram Negative Bacteria ◽  
Higher Doses

The influence of restricting gut-derived endotoxin availability on liver regeneration after partial hepatectomy was evaluated. Partial hepatectomy was performed by 67% liver resection of ether-anesthetized rats. Liver regeneration was quantified after partial hepatectomy by [3H]thymidine incorporation into hepatic DNA; endotoxemia due to absorption of endogenous endotoxin from the gut into the portal circulation was determined by qualitative lysate assay of perchloric acid-extracted plasma samples, and plasma levels of the hepatotrophic factors insulin and glucagon were measured by radioimmunoassay. Treatments to restrict gut-derived endotoxin included chronic gavage with neomycin and cefazolin for gut sterilization, chronic gavage with cholestyramine to bind endotoxin within the gut, subcutaneous administration of polymyxin B to neutralize the lipid A portion of circulating endotoxin, intraperitoneal induction of endotoxin tolerance by progressively higher doses of endotoxin, and experimentation with isolator-reared defined flora Fisher rats that were Gram-negative bacteria deficient and therefore endotoxin deficient. All treatments to restrict endogenous endotoxin impaired DNA synthesis in regenerating livers particularly 21 h posthepatectomy when replication was increasing most rapidly in normal rats. We hypothesize that impairment of DNA synthesis after partial hepatectomy in endotoxin-restricted animals was due to the observed lack of normal systemic endotoxemic as well as hyperinsulinemic and hyperglucagonemic responses to 67% liver resection.

scholarly journals THE EFFECT OF CORTISONE ON DNA CONTENT OF RAT HEPATOCYTES

1956 ◽  
Vol 2 (6) ◽  
pp. 711-724 ◽  
Author(s):  
Charles U. Lowe ◽  
Royden N. Rand
Keyword(s):  
Dna Synthesis ◽  
Dna Content ◽  
Present Report ◽  
Rat Hepatocytes ◽  
Degraded Dna ◽  
X Rays ◽  
Regenerating Liver ◽  
Cell Integrity ◽  
Liver Homogenates

Rats were treated with cortisone, x-radiation, and both agents in combination, and the effect noted on the DNA content of hepatocytes. Nuclei were enumerated both in whole liver homogenates and following isolation. The incorporation of P32 into DNA was also studied in relation to these agents. The following observations were made:— 1.The DNA content of nuclei fell both during cortisone administration and following x-radiation. In the former instance, the fall was progressive with continuing administration of hormone; in the latter instance, there was a return to normal 5 days after radiation. 2. Cortisone administration to x-radiated rats caused a fall in DNA/nucleus and prevented the return to normal at 5 days. 3. There was no evidence that the effects of cortisone and x-rays were additive in reducing DNA/nucleus. 4. These data indicate an alteration in DNA/nucleus, but simple changes in ploidy cannot be excluded. Either explanation requires that the agents used affect the DNA of non-regenerating nuclei. 5. Cortisone interfered with the incorporation of P32 into the DNA of regenerating liver. Only a small effect on DNA synthesis in resting liver was observed with cortisone or x-radiation. 6. DNA content of nuclei returned to normal 5 days after x-radiation and 3 days after discontinuance of cortisone. Slight increase in the incorporation of P32 by DNA was observed during recovery phases. 7. The hypothesis is proposed that the apparent losses and increases in DNA/nucleus were due to depolymerization and repolymerization of DNA. Following x-radiation and/or cortisone administration, it is proposed that some DNA is depolymerized and becomes cold acid-soluble and dissociated from organized chromatin. Later, conditions are such that this degraded DNA is repolymerized. 8. These data might be interpreted to indicate that a portion of the DNA is not essential to cell integrity; alternatively, there may be two or more species of DNA, one of which is more readily affected by the agents investigated in the present report.

Cholesterol metabolism in regenerating liver of the rat

1985 ◽  
Vol 249 (6) ◽  
pp. G679-G684 ◽  
Author(s):  
F. J. Field ◽  
S. N. Mathur ◽  
D. R. LaBrecque
Keyword(s):  
Dna Synthesis ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Cholesterol Synthesis ◽  
Cholesterol Metabolism ◽  
Reductase Activity ◽  
Plasma Cholesterol ◽  
Regenerating Liver ◽  
Acyltransferase Activity ◽  
Regenerating Rat Liver

The regenerating rat liver was used as a model to investigate the necessity for new cholesterol synthesis prior to the onset of cell division. Plasma cholesterol levels in partially hepatectomized rats were significantly decreased 24 and 48 h after surgery compared with levels in sham-operated animals. Hepatic cholesteryl ester content was also significantly increased in livers from partially hepatectomized animals, but the hepatic content of unesterified cholesterol was not affected. Hepatic triglyceride content was significantly increased within 6 h after surgery in the regenerating liver. The triglyceride levels reached a peak at 24 h, and by 72 h they had decreased back to levels that were no different from control. In the regenerating liver, microsomal 3-hydroxy-3-methylglutaryl CoA (HMG-CoA) reductase activity was increased 12 h after surgery. The activity of this enzyme remained significantly elevated throughout the 72-h period after surgery. In contrast, 12 h after partial hepatectomy the rate of hepatic cholesterol synthesis was significantly lower than that observed in livers from sham-operated rats. An increase in the rate of cholesterol synthesis was not observed until 48 h after partial hepatectomy, some 32 h after the start of DNA synthesis. Microsomal acyl-CoA:cholesterol acyltransferase activity was unchanged except for a 28% decrease at 72 h after partial hepatectomy. The data suggest that new cholesterol synthesis is not a requirement prior to the initiation of DNA synthesis in the regenerating rat liver.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Loss and reappearance of gap junctions in regenerating liver.

1978 ◽  
Vol 78 (2) ◽  
pp. 554-564 ◽  
Author(s):  
A G Yee ◽  
J P Revel
Keyword(s):  
Gap Junctions ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Rat Liver ◽  
Close Association ◽  
Freeze Fracture ◽  
Regenerating Liver ◽  
Bile Canaliculi ◽  
Zonulae Occludentes ◽  
Fracture Study

Changes in intercellular junctional morphology associated with rat liver regeneration were examined in a freeze-fracture study. After a two-thirds partial hepatectomy, both gap junctions and zonulae occludentes were drastically altered. Between 0 and 20 h after partial hepatectomy, the junctions appeared virtually unchanged. 28 h after partial hepatectomy, however, the large gap junctions usually located close to the bile canaliculi and the small gap junctions enmeshed within the strands of the zonulae occudentes completely disappeared. Although the zonulae occludentes bordering the bile canaliculi apparently remained intact, numerous strands could now be found oriented perpendicular to the canaliculi. In some instances, the membrane outside the canaliculi was extensively filled with isolated junctional strands, often forming very complex configurations. About 40 h after partial hepatectomy, very many small gap junctions reappeared in close association with the zonulae occludentes. Subsequently, gap junctions increased in size and decreased in number until about 48 h after partial hepatectomy when gap junctions were indistinguishable in size and number from those of control animals. The zonulae occludentes were again predominantly located around the canalicular margins. These studies provide further evidence for the growth of gap junctions by the accretion of particles and of small gap junctions to form large maculae.

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