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C Nadal

Publications and source records attributed to C Nadal.

At least 37 records · Page 2Linked to original sources
PubMed1986

Some aspects of the regulation of hepatocyte proliferation.

Studies of hepatocyte proliferation during physiologic growth of the rat and after experimental stimulations such as partial hepatectomy and injection of irritants show that an inhibitory mechanism is associated with decreasing proliferation and causes hepatocytes to be less sensitive to mitotic stimuli. An inhibitory glycopeptide linked to a high molecular weight protein, alpha 2-macroglobulin in man, has been characterized. This glycopeptide blocks the cell cycle of hepatocytes at the G1-S transition in vivo.

Animals↗
PubMed1985

[Inhibitory effect of human alpha 2-macroglobulin and a peptide released by trypsin, on the G1-S transition of hepatocytes in vivo].

Highly purified human alpha 2 M inhibits hepatocyte proliferation. 1 mg of alpha 2 M corresponds to 1 baby rat unit (BRU). alpha 2 M is bound to a low molecular weight glycopeptide, which is released during trypsinization of alpha 2 M. 3 micrograms of trypsin-treated alpha 2 M release 1 BRU. alpha 2 M and the glycopeptide have been shown to be identical, respectively, to high and low molecular weight components present in normal human plasma. Both components inhibit the G1-S transition of the hepatocyte cycle. alpha 2 M acts as an antagonist to the inhibitory effect of the glycopeptide when the molar ratio of trypsin to alpha 2 M is greater than 2.

Adult↗
PubMed1984

[Demonstration in human plasma of 2 factors inhibiting hepatocyte multiplication by blocking the cell cycle at the level of G1-S transition].

A factor which inhibits the G1-S transition of synchronized proliferating hepatocytes is detected in human serum or plasma. This activity is associated with an electronegatively charged component of high molecular weight in the native serum. Serum and plasma submitted to trypsin hydrolysis or to liver microsomes, release an ultrafiltrable component of low molecular weight which displays the same activity as the high molecular weight one from the native serum. This inhibitory system of hepatocyte proliferation is similar to that already described in Rat serum. It is species independent.

Adult↗
PubMed1983

Partial purification of rat and human serum factors inhibiting the G1-S transition in rat hepatocytes.

A low molecular weight compound, which inhibits the G1-S transition in rat hepatocytes, was purified from rat trypsin-treated serum by DEAE-cellulose chromatography and high-performance liquid chromatography on three different stationary phases. This procedure led to a 34500-fold purification with a 29% yield. Inactivation of the purified material by specific enzymes showed that the inhibitor is a glycopeptide containing a peptide moiety, N-acetylneuraminic acid and galactose residues. Amino acid analyses indicated the possible existence of a pentapeptide structure. The same purification procedure was applied to the corresponding human inhibitor. Inactivation by specific enzymes showed that it is also a glycopeptide.

Amino Acids↗
PubMed1983

Plasma levels of growth hormone, corticosterone and insulin, during induced hepatocyte synchronization in young rats.

A wave of synchronous hepatocytes entering the cell cycle can be obtained in vivo after a subcutaneous injection (e.g. of casein) in rats at around Post-natal Day 10, when plasma growth hormone (GH) levels reach a low plateau (40 +/- 2 ng/ml) and liver cell proliferation rate is high. The present work reports the following changes in plasma hormone concentrations after synchronization of 20% of the hepatocyte population: (1) during the G1 phase (i.e. 6-12 hr after the mitogenic trigger), plasma GH concentration has dropped further (25 +/- 1.5 ng/ml). It was back to 90% of control levels during the S phase, mitosis and the following response including a transitory decrease in labelling index below control values. Injected together with the irritating mitotic trigger, a single dose of rat GH reduced the cell synchronization and post-synchronization effects by 50%. (2) Plasma corticosterone levels varied inversely to those of GH, increasing to twice the control values during G1 and were back to physiological levels when synchronized hepatocytes entered the S phase. (3) Variations in insulin levels were similar to that of corticosterone, with narrower ranges and reduced amplitudes. Our data suggest a possible correlation between the observed variations in plasma hormone levels and the induced synchronous hepatocyte response.

Animals↗
PubMed1983

Rat serum factors inhibiting the G1-S transition in hepatocytes. II. Properties of the low molecular weight factor.

The properties were investigated of low molecular weight factors acting on the G1-S transition of baby rat hepatocytes. These factors were produced by incubating adult rat serum with trypsin or a 100,000 g liver microsomal fraction, and isolated by ultrafiltration. Enzyme degradation assays indicated that the active compound was in both cases a glycopeptide sensitive to pronase and papain and to the combination of neuraminidase and beta galactosidase. No loss of hepatocyte G1-S inhibitory activity was observed after heat treatment at pH 7.0. G50 gel filtration showed that both the G1-S inhibitory factors were collected in the last fractions eluted. The elution volume was slightly larger for the trypsin than for the microsomal-induced factor, suggesting a small difference between their molecular weight. These factors are believed to be glycopeptides with a molecular weight around 1400. They might be composed of a 3-sugar polysaccharide chain with a galactose preterminal and a neuraminic acid terminal, linked to a polypeptide chain of 6 to 8 amino acids.

Animals↗
PubMed1981

Rat serum factors inhibiting the G1-S transition in hepatocytes. I. Production of a low molecular weight inhibitor by proteases or liver fractions.

An attempt was made to detect the serum factors inhibiting the G1-S transition in synchronized, baby rat hepatocytes. In untreated adult rat serum, this inhibitory activity was always linked to high molecular weight (HMW) compounds. Incubation of serum with trypsin or chymotrypsin resulted in the formation of a low molecular weight (LMW) G1-S inhibitory factor. The same result was obtained with fractions from adult rat liver but not with kidney or spleen fractions. Separation of the LMW factor by ultrafiltration increased its specific activity by about 10(3). The active period in the cell cycle of both the LMW and HMW factors was the same: the late G1 phase. However, the activity of the LMW factor was not blocked by the Kunitz factor. An enzymatic transformation of the HMW factor might be induced by liver cell membrane-bound proteases and constitute a mechanism regulating hepatocyte proliferation.

Animals↗
PubMed1980

Lysosomal hydrolase activities in the developing rat liver.

The specific activity of three lysosomal proteinases (cathepsins B1, D, and L) as well as acid phosphatase and beta-galactosidase has been determined in the liver of both 7-10 day-old and young adult rats. Cathepsin B1 in suckling rats is markedly lower than in adults, while cathepsin D is only moderately lower and cathepsin L does not significantly differ. The activity of acid phosphatase is similar in the two groups of animals whereas that of beta-galactosidase in suckling rats is approx. twice as high as in adults. The activity of lysosomal hydrolases thus appears to be regulated individually during the development. Moreover it is suggested that the low activity of cathepsin B1 may be related to the low rate of cell protein catabolism characteristic of the developing liver (Conde and Scornik, 1977).

Acid Phosphatase↗
PubMed1979

Fluctuations in the level of liver cathepsins after partial hepatectomy.

Fluctuations in the level of liver cathepsins after partial hepatectomy were studied. The reduction in proteinase activities in dividing cells might conceivably reveal larger than that measured on the whole tissue since no more than 40-50% of residual liver cells takes part into the first mitotic wave after partial hepatectomy.

Animals↗
PubMed1979

Interference of sex-related factors in the response of liver cells to experimental mitotic stimuli.

Stimulation of liver cell multiplication was obtained under two different experimental conditions. (1) A single injection of casein solution resulted in (a) an identical synchronized mitotic wave response in 10-day old male and female rats and (b) a significantly lower response in adult male rats compared to females, a difference which was reduced by castration of males at birth but essentially maintained if animals were operated when 10 days old. (2) Partial hepatectomy shortly after puberty resulted in active hepatocyte multiplication occurring 3 hr earlier in females were ovariectomized at birth and significantly reduced when they were spayed at a later age. Hepatocytes of castrated females entered actively into S phase 2 hr later than the sham-operated controls. Unilateral ovariectomy on the other hand indicated that during compensatory and/or hypercompensatory activity of the single ovary there was a maximum difference between the male and female rate of [3H]thymidine uptake in liver nuclei 20 hr after hepatectomy. A further kinetic study (t = 25, 30,40, 65, 90 hr) indicated no significant sex-related difference in the number of S phases per 10,000 cells. The DNA content of regenerating versus control livers was comparable in both sexes at t = 22 and 90 hr but higher in females at t = 40 and 65 hr. A possible early postnatal interference of certain hormonal mechanisms in the receptivity to mitotic stimuli is postulated and discussed.

Animals↗
PubMed1977

Lysosomal enzyme activities in the regenerating rat liver.

The activity of four lysosomal enzymes (hyaluronidase, beta-N-acetylglucosaminidase, acid phosphatase, and cathepsin D) was studied in aqueous extracts of the light mitochondrial fraction of regenerating male rat liver. This tissue was chosen as a model for normal cell division in vivo. In the first wave of division, 40 to 50% of the cells divide synchronously. Activities were measured at 0, 9, 18 (end of G1 phase), 24 (S phase), and 30 hr (mitosis) and during regeneration, 4 and 11 days after partial hepatectomy. Activities were related to fresh tissue weight, to cellular DNA, and to protein content of the extracts. At 9 hr, there was an important increase in hyaluronidase and cathespin D activities (these two enzymes act upon macromolecules); beta-N-acetylglucosaminidase and acid phosphatase activities were only slightly increased. At the end of the G1 phase, 40 to 50% of the activity of all four enzymes was lost, which might indicate complete loss of activity in cells undergoing division. This depletion persisted until mitosis was complete. Four days later, there was a slow restoration of enzyme activities; after 11 days, hyaluronidase and cathepsin D exhibited about 80% of their initial activity, whereas beta-N-acetylglucosaminidase and acid phosphatase only regained about 50%. These results show that the lysosomal system perhaps plays some role in cell division.

Acetylglucosaminidase↗
PubMed1976

Inhibition of rat hepatocyte multiplication by serum and liver factors: physiological development and experimental induction.

Inhibition of the G1-S transition in synchronized baby rat hepatocytes was obtained by a subcutaneous injection of adult rat liver cytosol. This inhibitory activity was observed only with liver cytosol and not with kidney or spleen cytosol. The liver cell was a relatively specific target: no modifications were recorded in the kidney or submaxillary gland and inconsistant variations were found with tongue epithelium. The activity was associated with a non-dialysable factor. Physiological investigations support the opinion that the liver factor is the origin of the serum factor which had previously been described. Both factors were absent during the first three weeks of life. They appeared together during the 4th week in correlation with a decreasing rate of liver cell multiplication and then reached progressively their definitive adult levels. After 2/3 hepatectomy in adults, the liver cytosol retained its inhibitory activity, but the serum factor was reversibly neutralized by an antagonistic factor. Both inhibitory factors could be prematurely induced in baby rats and appeared transiently during the period of low mitotic activity following a wave of synchronized liver cells generated by an irritating stress. This inhibitory system is characteristic of the last developmental stages of the liver when growth decelerates before reaching a steady state. It seems to reduce the multiplication of hepatocytes by decreasing their sensitivity to stimuli initiating cell replication.

Age Factors↗
PubMed1975

Inhibition of rat hepatocyte multiplication by serum factors. Physiological significance.

A serum factor that inhibits the passage of hepatocytes from the G1 to the S phase and another that induces the production of binucleate hepatocytes were studied at different growth stages in the rat and under conditions inducing hepatocyte multiplication: partial hepatectomy and injection of irritants. A close relationship was found between the presence of these serum factors and the patterns of hepatocyte multiplication. When many S phase hepatocytes and few binucleate cells are produced in the liver, as in the first three weeks of life or after partial hepatectomy in adults, the mitotic inhibition and binucleate cell production activities are not found in the sera. Conversely, when the number of S phase hepatocytes decreases progressively and many binucleate cells are produced, as in weanling and adult rats or in baby rats during the late period after an irritating injection, these activities are present in the sera. These facts support the hypothesis that these factors play a role in the physiological regulatory mechanism of liver growth.

Animals↗
PubMed1975

Inhibitory and anti-inhibitory factors of rat serum active on the G1-S transition of hepatocyte cell cycle.

Rat hepatocytes are responsive to a serum factor inhibiting their progression through the cell cycle from the late G1 phase to the S phase. After fractionation of normal adult rat serum by two chromatographic steps on DEAE cellulose and sephadex gel filtration, the inhibitory activity was linked to proteins having a high electronegative charge and of apparent high molecular weight. Polyacrylamide gel electrophoretic analysis of active fraction showed that the alpha1 macroglobulin was its main component. Male and female baby rats were sensitive to the inhibitory factor from normal rats. Contrary to the normal adult rat serum the whole hepatectomized adult rat serum did not exhibit any ingibitory activity on the G1-S transition. However, two components having antagonist activities: an alpha1 globulin and a gamma globulin, were separated by chromatographic procedures from hepatectomized rat serum. (a) The alpha1 globulin showed an inhibitory activity. It had an apparent molecular weight lower than that found in normal rats. Its activity was sex related: only male baby rats were responsive. (b) The factor present in the gamma globulin fraction was found to be antagonistic to the alpha1 globulin factor. Its occurrence after hepatectomy explains the absence of inhibitory activity in the serum of hepatectomized rats.

Alpha-Globulins↗