[Caspase-2: what do we know today?].

Apoptosis (programmed cell death) is essential machinery for multicellular organisms. Apoptosis plays an important role in cell differentiation, damaged cell elimination and immune system homeostasis. This review is focused on various mechanisms of signal transduction through caspase-2 which believed to be one of the most enigmatical protease involved in apoptosis. Caspase-2 is activated upon stimulation by such agents as genotoxic stress, death receptors ligation, ER stress, metabolic changes, etc. In addition, caspase-2 may act as a tumor suppressor and has been implicated in cell response to oxidative stress and neurodegenerative progression during ischemic brain damage. Thus, variety of signal pathways triggered by caspase-2 place this protease apart from other members of the family and suggests a prominent role in apoptosis. Here, we analyse different functions of this unique caspase and discuss possible applications of accumulated knowledge in advanced oncology and medicine.

[Molecular mechanisms of radiation-induced cell death]. / Molekuliarnye mekhanizmy radiatsionnoi gibeli kletok.

Current data on the molecular mechanisms responsible for radiation-induced interphase death of lymphoid cells are presented. This radiobiological phenomenon is considered to be a special case of the general biological event of programmed cell death. Ionizing radiation and factors inducing terminal differentiation and programmed cell death are shown to activate some specific genes, whose products are needed for further steps of cellular self-destruction.

[Radiation disturbance of RNA metabolism during interphase death of lymphoid cells]. / Radiatsionnye narusheniia obmena RNK pri interfaznoi gibeli limfoidnykh kletok.

The data are reviewed concerning the radiation--induced disturbances of RNA metabolism in lymphoid cells. The role of the observed disorders in activation and realization of the interphase cell death program is discussed.

[Transcription of repeated and unique DNA nucleotide sequences in rat thymus cells stimulated with phytohemagglutinin]. / Transkriptsiia povtoriaiushchikhsia i unikal'nykh posledovatel'nostei DNK kletok timusa krbsy, stimulirovannykh fitogemaggliutininom

Transcription of unique and repeated DNA sequences in normal and phytohemagglutinin (PHA)-stimulated rat thymus cells is studied. It is found that heterogenous nuclear RNA (hnRNA) contains the transcript both from unique and repeat-d DNA sequences. PHA does not induce re-distribution of hnRNA fractions transcripted from different for their recurrency genome regions. Moreover, hnRNA from normal thymus cells competes with RNA from stimulated cells within the range of COt values (10(-3)-10(-4)) in which the hybridization has been carried out. It is concluded that no activation of new genome regions takes place in thymocytes.

[Study of the template properties and protein composition of the products of postradiation degradation of chromatin in the rat thymus]. / Issledovanie matrichnykh svoistv i belkovogo sostava produktov postradiatsionnoi degradatsii khromatina timusa krys.

In order to verify the assumption that the products of postirradiation degradation of the chromatin originate mainly at the genome sites active in transcription a study was made of the template activity of PDN, its sensitivity to DNAase I, and the protein composition of individual PDN fractions: The radiation-induced chromatin degradation in lymphoid cells was shown to occur in both the active and the repressed genome sites.

[Molecular mechanisms of interphase death of lymphoid cells. Distribution of transcribable sequences in products of the postradiation degradation of rat thymus chromatin]. / Molekuliarnye mekhanizmy interfaznoi gibeli limfoidnykh kletok. Raspredelenie transkribiruemykh posledovatel'nostei v produktakh posttradiatsionnoi degradatsii khromatina timusa krys.

The method of hybridization was used to study the presence of the transcribed sequences in PDN subfractions. As a component of mononucleosomes possessing a high electrophoretic motility DNA was enriched with the diverse unique transcribed siquences. It was shown that during the postirradiation degradation of the chromatin the mononucleosome fragments of PDN were mainly formed from the genome sites active in transcription whereas the high molecular weight fragments contained its repressed sequences.

[Molecular mechanisms of interphase death of lymphoid cells. Distribution of nuclease attack sites in chromatin and kinetic complexity of DNA in PDN]. / Molekuliarnye mekhanizmy interfaznoi gibeli limfoidnykh kletok. Kharakter raspredeleniia mest nukleaznoi ataki v khromatine i kineticheskaia slozhnost' DNK v sostave PDN.

On the basis of a quantitative correlation between single--and double-helix fragments of different length within PDN, a study was made of the pattern of distribution of the sites, attacked by nuclease, in the chromatin. It was shown that under the effect of ionizing radiation products of enzymic digestion of the chromatin. It was shown that under the effect of ionizing radiation products of enzymic digestion of the chromatin accumulated in thymocytes due to internucleosome degradation were excised from randomly localized genome sites. The analysis of the reassociation curves did not reveal distinctions in the kinetic complexity of the fractions of PDN and total DNA.

[Protein degradation during the interphase death of thymocytes induced by radiation and dexamethasone]. / Issledovanie degradatsii belkov pri interfaznoi gibeli timotsitov, indutsirovannoi radiatsiei i deksametazonom.

A study was made of protein degradation in rat thymocytes after exposure to ionizing radiation and dexamethasone. The pattern of degradation of 35S-methionine labelled proteins in gamma-irradiated cells and in those incubated in the presence of dexamethasone did not vary from that in control cells. No essential increase was noted in the intracellular protein degradation during interphase death of thymocytes.

[Biosynthesis of nuclear sap proteins in the thymocytes of irradiated rats]. / Biosintez belkov iadernogo soka v timotsitakh obluchennykh krys.

A study was made of biosynthesis of nuclear sap proteins in rat thymus cells exposed to 8 Gy gamma-radiation. Four hours following irradiation, changes were observed in the nuclear sap protein spectrum which were not associated with proteolysis.

[Radiation protective properties of a synthetic antagonist of glucocorticoids RU 38486]. / Issledovanie radiozashchitnogo deistviia sinteticheskogo antagonista gliukokortikoidov RU 38 486.

Radioprotective properties of synthetic antiglucocorticoid RU 38,486 were investigated. It was demonstrated that this antagonist of glucocorticoids possesses radioprotective effect in vitro and in vivo systems. Radioprotective properties at molecular level exhibited in inhibition of postirradiation endonuclease activation and in prevention of internucleosome chromatin degradation. Involvement of cytosol glucocorticoid receptors in initiation of radiation-induced programmed cell death is discussed.

[The spectra of de novo synthesized proteins in the early stages of radiation death of lymphocytes in the rat thymus]. / Issledovanie spektra de novo sintezirovannykh belkov na rannykh stadiiakh radiatsionnoi gibeli limfotsitov timusa krysy.

A comparative study was made of the spectrum of thymus cell proteins in the control and gamma-irradiated rats. It was shown that early after irradiation a group of proteins appeared in rat thymus cells which had not been traced, or detected in much lower amounts, in intact cells. Part of those polypeptides were referred to general stressor proteins, the other were specific for the effect of ionizing radiation. The spectrum of de novo synthesized enzymes changed with time after irradiation. Some of the proteins were found to induce chromatin degradation in the control cells and, presumably, to be involved in the implementation of the programmed cell death.

[Mechanism of thymocyte death in exposure to ultrahigh doses of gamma radiation]. / Issledovanie mekhanizma gibeli timotsitov pri vozdeistvii sverkhvysokikh doz gamma-izlucheniia.

A comparative study was made of the morphological and biochemical indices of rat thymus cells after gamma-irradiation with doses of 4-10 Gy (median), 20 Gy (high), and 200-400 Gy (superhigh). It was shown that 4 h after irradiation with superhigh doses the yield of polydeoxynucleotides (PDN) was twice as low as that observed after doses of 4-10 Gy. 24 h after irradiation the amount of the extracted PDN in thymocytes exposed to superhigh doses was markedly larger than that after 4 hours. After all doses applied chromatin degradation occurred at the internucleosome sites in a strict order, the activity of acid and alkaline nucleases being unchanged. A large number of cells have normal nuclear structure 4 h after irradiation (200-400 Gy), as was demonstrated by the electron microscopy data, while in 24 h no intact cells were virtually found in the thymus which correlated with the changes in the PDN yield. The mechanisms of the lymphoid cell death under the effect of different radiation doses are discussed.