Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “LIVER REGENERATION”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 199 records · Page 11Linked to original sources
PubMed1986

Enhanced production of dolichol, but not dolichyl phosphate, in the earliest stages of rat liver regeneration.

The regenerating liver presents a changed ability to use mevalonate 16 hr after partial hepatectomy. The dolichol content and its synthesis from mevalonate is increased, while no variation of dolichyl-P and ubiquinone parameters are detectable. The greater amount of mevalonate utilized to form dolichol, but not dolichyl-P, in this proliferating system, raises some questions about the physiological significance of these isoprenoid compounds and about their biosynthetic sequence.

Animals↗
PubMed1984

Effects of postoperative adjuvant chemotherapy on liver regeneration in partially hepatectomized rats.

Five-fluorouracil (5-FU) was given to rats at various periods following two-thirds hepatectomy and the effects of this drug on the regenerating liver were investigated. In one group of rats, two-thirds hepatectomy was carried out (Group I). In four other groups, 20 mg/kg 5-FU was given intravenously three times: 0, 24, 48 hours (Group II); 12, 36, 60 hours (Group III); 24, 48, 72 hours (Group IV); and 3, 4, 5 days (Group V) after the same operation. The peaks of DNA synthesis and mitoses of liver cells were noted on the first postoperative day in Groups I, IV and V. Persistent suppression and delay of DNA synthesis was induced in Groups II and III, while in Group IV, DNA synthesis and liver cell divisions were suppressed temporarily after the drug administration but recovered thereafter. There was no significant suppression in Group V. The serum albumin levels and survival rates paralleled the DNA synthesis. These results indicate that in case of postoperative adjuvant chemotherapy, great care must be directed to the time when DNA synthesis and mitosis of hepatocytes have not yet reached their peaks, because adjuvant chemotherapy in this period may be life-threatening.

Animals↗
PubMed1975

Effect of a single treatment with the alkylating carcinogens dimethylnitrosamine, diethylnitrosamine and methyl methanesulphonate, on liver regenerating after partial hepatectomy. II. Alkylation of DNA and inhibition of DNA replication.

Experiments were carried out to determine whether replication of alkylated DNA could be involved in the initiation of hepatocellular carcinoma which results from a single administration of dimethylnitrosamine (DMN) given after partial hepatectomy. The incidence of tumours is higher when DMN is given during the wave of DNA synthesis induced by the operation than when given in the early prereplicative stage. Therefore the alkylation of DNA in the regenerating liver by DMN given at these times and the effect of DMN on DNA synthesis were investigated. The extent, duration and pattern of alkylation of DNA, including the formation of 0-6-methylguanine, were similar whether DMN was given in the early pre-replicative stage (6 h after the operation) or during the period of DNA synthesis (at 24 h). DMN given a 6 h very greatly reduced the wave of DNA replication which would otherwise have ensued. When given at 24 h, by which time DNA synthesis was already taking place, DMN reduced the rate of incorporation of (-3H)thymidine after 1-2 h delay. However, in neither case was DNA synthesis reduced to the level occurring in normal intact liver. Treatment with diethylnitrosamine (DEN) at 6 h or at 24 h had a similar effect to DMN on the wave of DNA replication induced by partial hepatectomy. Methyl methanesulphonate (MMS given in the early pre-replicative stage delayed the wave of DNA synthesis by about 8 h, but when it did take place the extent of synthesis was as great as in untreated animals. When given during the period of DNA replication, MMS rapidly reduced the rate of synthesis. As in the case of the nitrosamines, synthesis was not reduced to the level occuring in normal intact animals. The difference from the nitrosamines lies in the nature of the alkylated bases formed in DNA. The fact that a single treatment with DMN induces cancer in partially hepatectomised animals but not in intact adult animals is not considered to be due to a gross difference in the nature of the alkylation of DNA. The experiments described support the concept that replication of DNA containing bases which are likely to mispair during replication may be necessary to 'fix' the lesion and thus cause a permanent inheritable change in the genetic material.

Alkylation↗
PubMed1989

Interaction of ketosis and liver regeneration in the rat.

Monoacetoacetin, the monoglyceride of acetoacetate, was investigated as a nutritional support for the regenerating liver. Following partial hepatectomy, rats were either fed an oral diet ad libitum or administered by total parenteral feeding glucose alone, monoacetoacetin-glucose mixture, or lipid emulsion-glucose for the nonprotein calories. Five rats from each treatment were killed at 6-hr intervals beginning 12 hr after partial hepatectomy and ending at 72 hr. The number of cells synthesizing DNA and the number of cells in mitosis were compared. Rats fed orally or infused with glucose alone or with lipid emulsion had similar parameters throughout. Rats infused with monoacetoacetin had approximately double the number of cells in mitosis and DNA synthesis compared to the other treatments. This stimulation by monoacetoacetin persisted 72 hr. It was concluded from the data that acetoacetate was the agent responsible for increased DNA synthesis and mitosis, but the mechanism for the stimulation was not identified.

3-Hydroxybutyric Acid↗
PubMed1992

Gene expressions and activities of protein phosphatases PP1 and PP2A in rat liver regeneration after partial hepatectomy.

We have examined the levels of gene expressions and activities of protein phosphatases, PP1 and PP2A, in rat regenerating livers. PP1 alpha mRNA started to increase from 6 h after partial hepatectomy (PH) and showed two peaks at 12 and 48 h. PP2A mRNA level showed two peaks at 6 and 10-12 h. Protein phosphatase activities were determined both in non-nuclear fraction and in nuclei. While spontaneous PP1 activity in non-nuclear fraction was nearly constant, potential PP1 activity revealed by Co(2+)-trypsin treatment showed a small peak between 7 and 12 h. In nuclei, both spontaneous and potential PP1 activity began to increase from 4-7 h after PH, reached a maximum (about 2.5-fold over control levels) at 12 h, the time which corresponds to the G1 to S transition in the cell cycle, and then declined back to control levels by 7 days. PP2A activity in non-nuclear fraction was nearly constant in both spontaneous and potential forms. PP2A activity in both forms in nuclei was very low throughout. These results suggest the possibility that PP1 in nuclei plays some role in the G1 to S transition in the cell cycle of hepatocyte proliferation.

Animals↗
PubMed1998

Use of proliferating cell nuclear antigen as a marker of liver regeneration after partial hepatectomy in rats.

In order to document and compare proliferating cell nuclear antigen (PCNA) mRNA and protein levels with more traditional parameters of hepatic regenerative activity in a rat model, adult male Sprague-Dawley rats (4 to 6 per group) were killed at various times up to 96 hours after 70% partial hepatectomy. At each time interval, tissue PCNA mRNA abundance and protein levels were documented (by Northern and Western blot analysis, respectively) and compared with the results of PCNA immunostaining and 3H-thymidine incorporation into hepatic DNA. Tissue PCNA protein levels were also documented in additional groups of rats 12, 24, 36, and 48 hours after sham or 30% partial hepatectomy. PCNA mRNA expression after partial hepatectomy was variable: almost undetectable at 24 hours, levels returned to baseline at 36 hours, then fell again to low levels at 96 hours. PCNA protein levels remained stable for 36 hours, increased to fourfold above baseline (p < 0.01) at 48 hours, then remained elevated for the duration of the 96-hour study. Changes in PCNA by immunostaining were similar but tended to occur somewhat earlier (significant increases being detectable at 24 hours), whereas 3H-thymidine incorporation detected the earliest increases in DNA synthesis at 12 hours and peaked at 36 hours. Peak PCNA protein levels correlated with the extent (0%, 30%, or 70%) of hepatic resection. The results indicate that PCNA protein level as determined by Western blot analysis, but not PCNA mRNA expression, correlates with PCNA immunostaining and 3H-thymidine incorporation in the regenerating liver. These findings support the use of PCNA protein determinations as an additional quantitative measure of hepatic regenerative activity after partial hepatectomy in rats.

Animals↗
PubMed1999

Quercetin inhibited DNA synthesis and induced apoptosis associated with increase in c-fos mRNA level and the upregulation of p21WAF1CIP1 mRNA and protein expression during liver regeneration after partial hepatectomy.

Quercetin, a widely distributed bioflavonoid, inhibited DNA synthesis in regenerating liver after partial hepatectomy. This inhibition was accompanied by apoptosis, evidenced by in situ end-labeling and gel electrophoresis of DNA fragmentation. Characteristic DNA fragmentation was detected as early as 2 h after injection. Northern blot analysis revealed that quercetin induced the increases in c-fos and p21WAF1CIP1 mRNA levels within 2 h. The expression of p21 protein was also enhanced, while p53 mRNA and protein levels were not affected by quercetin. These results suggest that quercetin-induced apoptosis is associated with the increase in c-fos mRNA level and the upregulation of p21 mRNA and protein expression, probably in a p53-independent pathway.

Animals↗
PubMed2003

Circadian rhythms. Liver regeneration clocks on.

In some simple protozoans and unicellular algae, the cell cycle clock is strongly influenced by the circadian clock, such that mitotic cell division takes place only at certain times of the day. Now, as Schibler reports in his Perspective, new work on regenerating liver cells in mice (Matsuo et al.) reveals that the cell cycle clock of mammalian cells is also under the yoke of the master circadian oscillator.

ARNTL Transcription Factors↗
PubMed1992

Interactions among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration.

In regenerating liver, a physiologically normal model of cell growth, LRF-1, JunB, c-Jun, and c-Fos among Jun/Fos/LRF-1 family members are induced posthepatectomy. In liver cells, high levels of c-Fos/c-Jun, c-Fos/JunB, LRF-1/c-Jun, and LRF-1/JunB complexes are present for several hours after the G0/G1 transition, and the relative level of LRF-1/JunB complexes increases during G1. We provide evidence for dramatic differences in promoter-specific activation by LRF-1- and c-Fos-containing complexes. LRF-1 in combination with either Jun protein strongly activates a cyclic AMP response element-containing promoter which c-Fos/Jun does not activate. LRF-1/c-Jun, c-Fos/c-Jun, and c-Fos/JunB activate specific AP-1 and ATF site-containing promoters, and in contrast, LRF-1/JunB potently represses c-Fos- and c-Jun-mediated activation of these promoters. Repression is dependent on a region in LRF-1 that includes amino acids 40 to 84 (domain R) and the basic/leucine zipper domain. As the relative level of LRF-1/JunB complexes increases posthepatectomy, c-Fos/Jun-mediated ATF and AP-1 site activation is likely to decrease with simultaneous transcriptional activation of the many liver-specific genes whose promoters contain cyclic AMP response element sites. Thus, through complex interactions among LRF-1, JunB, c-Jun, and c-Fos, control of delayed gene expression may be established for extended times during the G1 phase of hepatic growth.

3T3 Cells↗
PubMed1992

Effect of endotoxin on rat liver regeneration after partial hepatectomy.

Lipopolysaccharide administered intraperitoneally to rats just after partial (70%) hepatectomy at the dose from 0.04 to 4 mg/kg body weight inhibited the induction of thymidylate synthase and thymidine kinase which are rate-determining enzymes of DNA synthesis, resulting in the impairment of DNA synthesis in the regenerating liver. This effect may be due to the hepato-toxic nature of endotoxin.

Animals↗
PubMed1989

[Change in the number of epidermal growth factor receptors of hepatocytes during liver regeneration in rats].

The number of epidermal growth factor (EGF) receptors was determined for rat's hepatocytes under condition of their regeneratory proliferation, following a partial hepatectomy. In the normal hepatocytes two classes of EGF-receptors are distinguished, with high and low affinity, respectively. As early as 2 hours after the partial hepatectomy the total number of EGF-receptors sharply decreases, those with high affinity being not determined at all. The patterns of autophosphorylation of EGF-receptors with low affinity, examined in regenerating liver hepatocytes, remained the same as in the intact liver: their kinase activity was EGF-dependent, tyrosine residues of receptor molecules, with molecular mass equal to 150-170 kDa, underwent phosphorylation.

Animals↗
PubMed1982

Liver regeneration studies with rat hepatocytes in primary culture.

Adult rat parenchymal hepatocytes in primary culture can be induced to enter into DNA synthesis and mitosis. The optimal conditions for hepatocyte replication are low plating density (less than 10,000 cells/sq cm) and 50% serum from two-thirds partially hepatectomized rats (48 hr after hepatectomy). Approximately 80% of the hepatocytes enter the cell cycle, and most of these cells go through mitosis. The replicating hepatocytes remain positive for glucose-6-phosphatase and negative for gamma-glutamyl transpeptidase, and they accumulate fat, in analogy to regenerating liver. Most of the replicating hepatocytes enter into multiple consecutive rounds of DNA synthesis. Dose-response studies between control animal serum and hepatocyte labeling index indicate that in unoperated animals the serum contains substances stimulatory as well as inhibitory for hepatic growth, with the inhibitory effect prevailing at high concentrations. After partial hepatectomy, the inhibitory activity disappears whereas the hepatopoietin activity reaches almost 90% of maximal biological effectiveness at 25% serum concentration. Addition of hormones to the system shows that the hepatopoietin activity is not identical to epidermal growth factor, platelet-derived growth factor, thyroxine, glucagon, or hydrocortisone. Norepinephrine abolishes the difference between control and hepatectomized serum but does not restore hepatopoietin activity when added to heat-inactivated serum. The results show that this system of replicating hepatocytes can be used to investigate the trophic factors that control growth of normal and neoplastic hepatocytes.

Animals↗
PubMed1980

[some features of nuclear genome transcription at early stages of liver regeneration. RNA-polymerase activity of isolated nuclei].

The RNA-polymerase activity of isolated nuclei after 1, 3, 6, 12 and 24 hrs following partial hepatectomy was studied. The enzyme activity showed almost a 2-fold decrease after the first post-operative hour, followed by an increase of activity which reached its maximum after 6 hrs. A decrease of nuclear hepatocyte RNA-polymerase sensitivity to alpha-amanitine after 1 and 3 hrs following the surgery was found. After 6 hrs the enzyme was activated by alpha-amanitine. Using selective incorporation of four labelled ribonucleoside triphosphates, it was shown that alpha-amanitine causes a shift in the nucleotide composition of RNA synthesized in the regenerating liver towards the AU-type RNA.

Amanitins↗
PubMed2006

Delayed liver regeneration in mice lacking liver serum response factor.

Various immediate early genes (IEGs) upregulated during the early process of liver regeneration are transcriptional targets of the serum response factor (SRF). We show here that the expression of SRF is rapidly induced in rodent liver after partial hepatectomy. Because the inactivation of the SRF gene in mice is embryonic lethal, the in vivo role of SRF in liver regeneration after partial hepatectomy was analyzed in mutant mice conditionally deleted for SRF in the liver. We demonstrate that SRF is not an essential factor for liver ontogenesis. However, adult mutant mice show impaired liver regeneration after partial hepatectomy, associated with a blunted upregulation of various SRF target IEGs. In conclusion, our work suggests that SRF is an early response transcription factor that may contribute to the initial phases of liver regeneration through its activation of IEGs.

Animals↗
PubMed1994

The cellular reproduction in physiological and reparative liver regeneration.

The liver regeneration of male rats was examined autoradiographically under physiological and reparative conditions. The reparative regeneration was induced by a single injection of allylalcohol intraperitoneally. In both forms of regeneration a displacement of tritiated thymidine-marked hepatocytes from the periportal field to the perivenous field of the liver acinus could be recognized. The velocity of the cell migration after allylalcohol administration was higher than under physiological conditions. Physiological and reparative liver regeneration do not exclude each other but obviously coexist. A more intensively to be examined hepatocellular stem cell concept gains importance.

Animals↗
PubMed1986

Transcriptional switch from albumin to alpha-fetoprotein and changes in transcription of other genes during carbon tetrachloride induced liver regeneration.

During liver regeneration induced by CCl4 administration to rats, changes in the relative transcription rates of albumin and alpha-fetoprotein genes have been measured in conjunction with other liver-specific and general cellular function genes. Within 24 h following CCl4 administration, albumin gene transcription decreases by 85%, whereas alpha-fetoprotein transcription increases from undetectable levels to 50% of that observed for albumin. These changes precede maximal [3H]thymidine incorporation into DNA which peaks at 48 h. Other genes related to liver-specific functions, such as ligandin, alpha 1-antitrypsin, and cytochrome P-450's, as well as general cellular genes pro alpha 1- and pro alpha 2-collagen, beta-actin, and alpha-tubulin, respond in kinetic patterns often distinct from each other and from albumin and alpha-fetoprotein. Changes in the steady-state levels of albumin and alpha-fetoprotein mRNA correlate with changes in transcription, but there is a lag in alpha-fetoprotein mRNA accumulation, which peaks at 72 h following CCl4 administration. These studies indicate that reciprocal changes in albumin and alpha-fetoprotein gene transcription occur during CCl4-induced liver regeneration, leading to changes in the level of these specific mRNAs. These changes precede DNA synthesis and would appear to represent an alteration in differentiated function of hepatocytes in conjunction with the liver regenerative process.

Actins↗
PubMed1997

Specific activation of AP-1 but not Stat3 in regenerating liver in mice.

Liver regeneration following partial hepatectomy is regulated by hepatotrophic factors whose precise roles are still elusive. In cell culture studies, some of them have been shown to activate members of the family of the signal transducers and activators of transcription (Stat). To test this contention in vivo, nuclear extracts were isolated from livers of partially hepatectomized and sham-operated mice killed at 30 different time points between zero and 108 h after surgery. Stat3 DNA binding is rapidly induced after surgery in both partially hepatectomized and sham-operated mice. Maximum activation of Stat3 is achieved 4-6 h after resection, and elevated Stat3 activation is detected as late as 60 h after surgery in both groups. Activated Stat5 is found sporadically in both sham-operated and resected mice but appears to be absent in the first 12 h after partial hepatectomy. Neither Stat1, Stat2, Stat4 nor Stat6 is induced during the time of observation. In contrast, AP-1 DNA binding activity is specifically induced in regenerating mouse liver.

3T3 Cells↗
PubMed1987

Biliary lipid secretion in the regenerating liver of the rat.

The effect of two-thirds hepatectomy on biliary lipid secretion was studied in fasted rats. Bile acids, cholesterol and phospholipids were determined in the bile of rats with biliary drainage. Bile acid and phospholipid concentrations were not significantly modified during liver regeneration but there was a significant decrease in cholesterol concentrations in bile at 12 h after hepatectomy, with a gradual return to normal values. The molar percentage of cholesterol and the calculated lithogenic index of bile were also significantly decreased by 12 h. The biliary secretion of bile acids and phospholipids, expressed per gram of liver, showed a tendency to increase regeneration, but cholesterol secretion was significantly decreased from 12 to 48 h following liver resection. Some possibilities to explain the uncoupling between cholesterol secretion and bile acid secretion are discussed.

Animals↗