Interferon-γ effect on growth regulation of cells with different levels of EGF receptor expression

Interferon gamma (IFNγ) is known to inhibit the proliferation of some transformed cell lines. Recently, we demonstrated the transactivation of the epidermal growth factor receptor (EGFR) in response to IFNγ (Burova et al., 2007) and provided direct evidence for the dependence of IFNγ-induced EGFR transactivation on the EGFR expression level in epithelial cells (Gonchar et al., 2008). This study examines an antiproliferative effect of IFNγ on human epithelial cell lines—A431 and HeLa that express high levels of EGFR, as well as HEK293 that expresses low levels of EGFR. To characterize the IFNγ-induced changes in these cells, we studied cell growth, the cell cycle, and induction of apoptosis. The response to IFNγ differed in the compared cell lines; cell growth was inhibited in both A431 and HeLa cells, but not in HEK293 cells, as was shown by the cell count and MTT. The cell-cycle phases analyzed by flow cytometry were disturbed in A431 and HeLa cells in response to IFNγ. On the contrary, in HEK293 cells, the IFNγ treatment did not alter distribution by cell cycle phases. Our results indicate that IFNγ produces an antiproliferative effect that depends on the increased expression of EGFR in A431 and HeLa cells. Furthermore, it was demonstrated that IFNγ induced the caspase 3 activation in A431 cells, which suggests the involvement of active caspase 3 in the IFNγ-induced apoptosis.     

Gold nanoparticles disturb nuclear chromatin decondensation in mouse sperm in vitro

The effect of gold nanoparticles on mouse epididymal sperm has been studied using the model system of nuclear chromatin decondensation in vitro. It is shown that the treatment of gametes, preliminary membrane-freed by sodium dodecyl sulfate, in the mediums containing gold nanoparticles (with diameter ∼2.5 nm) in concentrations 1.0 × 10¹⁵ or 0.5 × 10¹⁵ particles/ml and following incubation in dithiothreitol solution (DTT) resulted in failure of chromatin decondensation process and nucleus structure. We conclude that gold nanoparticles possess spermatotoxicity. The mechanism of cytotoxic effect of gold nanoparticles may be related with their interaction with molecules of double-helix DNA. The model system studied in this research is applicable for further investigations of cytotoxic effects of nanoparticles of different origin and made of different metals.     

Mechanisms of induced processes in aqueous hemoglobin solutions at 77 K

ESR spectra of gamma-irradiated and frozen at 77 K human oxyhemoglobin and partially denaturated methemoglobin solutions were analysed. The quartet signal ascribed to the anion-radical of proximal histidine was shown to dominate in the spectra of both solutions. The spectra of methemoglobin solution irradiated with relatively small doses have an intensive singlet ascribed to the stabilized electron. The formation mechanism of free radicals is discussed.     

EFFECTS OF LEUCINE ON BRAIN SEROTONIN

Abstract— The effect of excess leucine in the diet on serotonin metabolism in the brain was investigated in experimental animals. It was found that:
(1) Animals receiving diets containing 3 % and 8 % leucine and those receiving jowar diets had significantly lower levels of serotonin in the brain.
(2) Intraperitoneal administration of the precursor amino acid 5-HTP increased the serotonin concentration in brain in both control and leucine-fed animals. However, the serotonin concentration in leucine-fed animals was significantly lower than that of pairfed controls. Larger amounts of the synthesized serotonin were found to be catabolized in 3 hr in leucine-fed animals than in control animals.
(3) The in vitro uptake of [¹⁴C]5-HTP by brain slices of animals fed leucine was found to be similar to that of control animals.
(4) The basal concentration of 5-HIAA in brain was higher in leucine-fed animals, suggesting a higher rate of catabolism of serotonin.
(5) Administration of nicotinic acid resulted in a further fall of serotonin concentration in the brains of leucine-fed animals but not in control animals.     

Genetische Aspekte bei Spermatogenesestörungen

The cause for infertility which affects about 10–15% of all couples may be found in approximately half of the cases in the male partners who usually exhibit reduced sperm counts in the ejaculate (i.e. oligozoospermia or azoospermia). The clinically most relevant genetic causes of spermatogenic failure are chromosomal aberrations including Klinefelter’s syndrome and Y chromosomal microdeletions of the AZF loci. Aside from the full clinical picture of cystic fibrosis, mutations in the CFTR gene can cause an isolated obstructive azoospermia without spermatogenic impairment. Genetic investigations should depend on the results of andrological examinations. Chromosomal aberrations are detected more frequently with decreasing sperm counts, where autosomes (e.g. translocations) are predominantly involved in men with oligozoospermia whereas in 10–15% azoospermia is caused by Klinefelter’s syndrome. Classical AZF deletions are found only in men with severe oligospermia or azoospermia and have a prognostic value. In contrast to men with AZFc deletions, carriers of complete AZFa and AZFb deletions have virtually no chance for testicular sperm extraction and a testicular biopsy is not advised. Rare cases of male infertility may be caused by specific syndromes or sperm defects (e.g. globozoospermia and disorders of ciliary structure).