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Biomedical subjects

T M Astakhova

Publications and source records attributed to T M Astakhova.

10 recordsLinked to original sources

Peculiarities of proteasome pool formation in rat spleen and liver during postnatal development.

Changes in the specific activity and amounts of 26S and 20S proteasome pools in rat spleen and liver during postnatal development and appearance in them of immune subunits were studied. Two decreases in chymotrypsin-like activity of the proteasome pools were recorded during the first three weeks after birth. The activity minimum fell on the 11th and 19th days, and the first decrease was more prolonged and pronounced than the second. The decrease in the specific activity of the 26S proteasome pools was associated with a reduction of their quantity. The 20S proteasome pools displayed no such decreases. Noticeable quantities of immune subunits LMP7 and LMP2 were revealed by Western blotting in the spleen on the 7th day and on the 19th day in the liver, concurrently with the beginning of the decrease in the proteasome activity. It was concluded that during the first three weeks of postnatal development the proteasome pools in rat spleen and liver were replaced twice, and in the spleen (a lymphoid organ) a qualitatively new pool containing immune subunits appeared nearly two weeks earlier than in the liver (a non-lymphoid organ). The appearance of immune proteasomes in different organs and tissues during some weeks after birth seems to explain the immune system inefficiency during embryogenesis and early postnatal development.

Animals↗

[Sex hormone receptors, prostaglandins and cAMP, in functional activity of the uterus].

The levels of progesterone and estrogen receptors, cAMP and prostaglandins E2 and F2 alpha were studied in the decidua of pregnant women, which was obtained during surgical, spontaneous or prostaglandin-induced abortion or by pregnancy termination with vacuum aspiration after RU-486 treatment (before the onset of abortion). Our data have allowed the authors to suggest that (i) for the maintenance of normal activity of decidua during pregnancy, the following points are considerably important: the constant ratio of progesterone and estrogen receptors in favor of progesterone receptors, low PG levels and high cAMP levels; (ii) both spontaneous and induced abortion are characterized by decreases in the levels of progesterone receptor (which in turn changes the ratio of progesterone and estrogen receptors in favor of the latter), by increased PG levels and decreasing cAMP concentrations.

Abortion, Induced↗

[Prostaglandin content in decidual tissue of women in spontaneous abortion].

Prostaglandins E2 and F2 alpha were measured in decidual tissue of women after spontaneous abortions at pregnancy terms 8 to 10 weeks and after abortions induced by sulprostone, a synthetic prostaglandin E2 analog, at pregnancy term 4-5 weeks. Women in whom pregnancy was terminated surgically at relevant periods were controls. Prostaglandin E2 concentration was found to be 5 times higher and that of prostaglandin F2 alpha 40 times higher in women with spontaneous abortions than in surgical abortion. In sulprostone-induced abortion prostaglandin concentrations in decidual tissue were the same as in controls. These data indicate that a drastic increase of prostaglandin levels in spontaneous abortion is not only a result of myometrial contractions or decidual tissue rejection, but an important component in the chain of events leading to miscarriage.

Abortifacient Agents, Nonsteroidal↗

The effect of RU486 on progesterone and oestrogen receptor concentration in human decidua on early pregnancy.

Concentrations of progesterone receptor (PR) and oestrogen receptor (ER) were measured by radioligand assay in decidual tissue of women undergoing termination of early pregnancy (amenorrhoea up to 49 days). Pregnancies were terminated by vacuum aspiration at 12 or 36 h after oral administration of placebo or antiprogestin RU486 in different doses. Treatment with RU486 decreased decidual PR content, the effect being observed at 12 h as well as at 36 h after 600 mg RU486 and at 36 h after 3 x 25 mg RU486 given at 12 h intervals. PR concentration 12 h after a single dose of 25 mg RU486 was not affected. ER content was unchanged at 12 h after RU486 but increased 36 h after 600 mg and 3 x 25 mg RU486. Our data suggest that apart from blocking progesterone action, RU486 may exert its abortifacient effect through decreasing the PR concentration. The simultaneous decrease of PR concentration and an increase of ER concentration changes the balance between them in favour of ER, which might also play a role in the abortifacient effect of RU486.

Cell Nucleus↗

[Multiple forms of the proteasomes and some approaches to their separation].

A technique for proteasome isolation from rat liver was developed; it allows isolation of 26S proteasome fraction free from 20S proteasome admixture. The technique includes consecutive stages of protein fractionation by different concentrations of ammonium sulfate, gel filtration on Sepharose 2B, and high-speed ultracentrifugation.

Ammonium Sulfate↗

[Changes in proteasome activity and subunit composition during postnatal development of rat].

The dynamics of the activities of 26S and 20S proteasomes in the rat liver and spleen have been studied during postnatal development from 1 to 90 days. The activities of proteasome forms both in spleen and in liver increased in adult animals as compared to one day rats. The activities of both proteasome forms in the liver did not differ significantly from those in the spleen at all stages of postnatal development. Using Western blot with monoclonal antibodies to Rpt6 subunit, we confirmed the presence of 26S proteasome in both organs at all stages of postnatal development. Studies with polyclonal antibodies to beta1i (LMP2) subunit showed the appearance of the immune subunit in the spleen by day 9 and in the liver only by day 23 of postnatal development. This result suggests the earlier formation of the spleen as an organ with immune functions.

Animals↗

[Exclusion of immune proteasomes from mouse ascitic carcinoma Krebs-II cells].

Pools of 26S and 20S proteasomes were studied in the spleen, liver, lung, and ascitic carcinoma Krebs-II of mouse. Western blotting demonstrated that the pool of 26S proteasomes in ascitic carcinoma Krebs-II was twice that in control lung cells and did not significantly differ by total 26S proteasome quantities from the spleen and liver. At the same time, the level of immune subunit LMP7 was 12 times lower in it compared to lung proteasomes and 4-5 times lower compared to spleen and liver proteasomes. Immune subunit LMP2 was undetectable by this technique in the ascitic carcinoma in contrast to the lung, spleen, and liver. All immune subunits in the studied organs and ascitic carcinoma Krebs-II are components of 26S but not 20S proteasomes.

Animals↗

[The effect of the synthetic analog of prostaglandin E2 sulprostone on the adenylate cyclase system in decidual tissue of women].

Activities of adenylate cyclase and phosphodiesterase were studied in decidual tissue of women, pregnancy of which was interrupted within the first term by means of synthetic analogue of prostaglandin E2 sulprostone; decidual tissue obtained after surgical abortion served as a control. Content of cAMP in decidual tissue was decreased 4-fold after administration of sulprostone. At the same time, activity od adenylate cyclase was decreased 2-3-fold, while activity of phosphodiesterase was unaltered. These data suggest that the decrease in cAMP concentration occurred as a result of inhibition of its synthesis. After administration of sulprostone the adenylate cyclase activity was decreased 3- and 4.5-fold in response to specific stimulators NaF and forskolin, respectively, thus indicating that content and activity of G protein, and apparently of catalytic subunits, were decreased. Long-term effect of prostaglandins on decidual tissue appears to cause a heterologous desensitization of adenylate cyclase and this phenomenon is responsible for pharmacologic action of prostaglandins.

Abortifacient Agents↗

[Estrogen and progesterone receptors in the decidual tissue of women administered prostaglandins and experiencing spontaneous abortion].

A study was made of the content of estrogen and progesterone receptors (ER and PR, respectively) in the cytosol and nuclei of the decidual tissue of women in induced and spontaneous abortion at 7-12 week pregnancy. Abortion was done surgically (control group) and in preliminary cervical dilatation with the help of intravaginal suppositories with a synthetic prostaglandin analog of E1-16.16-dimethyltrans-delta 2-PGE1 (ONO-802) group or laminaria. The level of ER in the cytosol and nuclei of the decidual tissue of the control group was twice as low as that of PR, and the ER/PR ratio in cell fractions as well as in general cell receptors was 0.58 +/- 0.09, 0.42 +/- 0.07 and 0.56 +/- 0.07, respectively. The suppositories with ONO-802 caused a statistically significant decrease in the PR content in each of the cell fractions and cytoplasmic ER resulting in an increase in the ER/PR ratio to 0.87 +/- 0.06 (P less than 0.05) in the cytosol, 0.09 +/- 0.24 (P less than 0.05) in the nuclei, and 0.86 +/- 0.8 (P less than 0.05) in the total cell. A decrease in the PR level in both cell fractions and the ER level in the fraction of the nuclei with an acute increase in the content of cytoplasmic ER was marked in spontaneous abortion. The ER/PR ratio also rose to ER and was 1.98 +/- +/- 0.2 (P less than 0.001) in the cytosol and 1.02 +/- 0.16 (P less than 0.05) in the total cell. It was concluded that an absolute and/or relative decrease in the PR level plays an important role in mechanism of abortion.

Abortifacient Agents, Nonsteroidal↗