Akt Activation Emulates Chk1 Inhibition and Bcl2 Overexpression and Abrogates G2 Cell Cycle Checkpoint by Inhibiting BRCA1 Foci

Akt is perhaps the most frequently activated oncoprotein in human cancers. Overriding cell cycle checkpoint in combination with the inhibition of apoptosis are two principal requirements for predisposition to cancer. Here we show that the activation of Akt is sufficient to promote these two principal processes, by inhibiting Chk1 activation with concomitant inhibition of apoptosis. These activities of Akt cannot be recapitulated by the knockdown of Chk1 alone or by overexpression of Bcl2. Rather the combination of Chk1 knockdown and Bcl2 overexpression is required to recapitulate Akt activities. Akt was shown to directly phosphorylate Chk1. However, we found that Chk1 mutants in the Akt phosphorylation sites behave like wild-type Chk1 in mediating G2 arrest, suggesting that the phosphorylation of Chk1 by Akt is either dispensable for Chk1 activity or insufficient by itself to exert an effect on Chk1 activity. Here we report a new mechanism by which Akt affects G2 cell cycle arrest. We show that Akt inhibits BRCA1 function that induces G2 cell cycle arrest. Akt prevents the translocation of BRCA1 to DNA damage foci and, thereby, inhibiting the activation of Chk1 following DNA damage.     

The biological effects in animals related to the accident at the Chernobyl Atomic Electric Power Station. 1. The experimental model. The radiation loads on animals kept continuously under external and internal radiation exposure in the area of the Chernobyl Atomic Electric Power Station]

Irradiation conditions in which laboratory animals were kept in experimental laboratories of Chernobyl and Kiev after the accident at the Chernobyl A.P.S. are described. The data are presented on the spectral structural and activity of radionuclides in the diet as well as in the organs and tissues of the animals. The radiation loads have been estimated with regard to an external gamma component and the internal one contributed by the incorporated radionuclides. It has been shown that radiation doses received by the animals during their lifetime due to these contributions do not exceed units of cGy.     

Spectrofluorimetric determination of biogenic amines (serotonin, dopamine) in Metechinorhynchus salmonis (Acanthocephala)

Identification of serotonin and dopamine in M. salmonis was conducted by means of some fluorometric methods. The presence of negligible amount of a serotonin-like component and substance close in its spectral characteristics to dopamine was shown.     

The effect of administering corticoliberin into the striatum on the open-field and shuttle-box behaviors of KHA and KLA strain rats]

The effects of corticotropin-releasing hormone (CRH) injected into the dorsal neostriatum on the open-field and shuttle-box behavior were studied in rats with high (Koltushi high avoidance, KHA) and low (Koltushi low avoidance, KLA) capability for avoidance learning. The effects of this hormone on the behavior of these rat strains were different. In KLA rats with passive strategy of behavior the CRH injection led to a rapid locomotor activation in the open field, while the rats with active behavioral strategy (KHA) reacted to the injection by a significant decrease in locomotion and change for the passive mode of behavior. The same CRH effects on locomotion were obtained in the shuttle-box experiments. Moreover, in the KLA rats the neurohormone injection resulted in an improvement of avoidance learning in contrast to the KHA rats, in which CRH substantially impaired avoidance learning. The obtained evidence is discussed in terms of the important role of striatal CRH in the choice of behavioral strategy in stress.