NAP Family CG5017 Chaperone Pleiotropically Regulates Human AHR Target Genes Expression in Testis.

To study the regulatory mechanism of the Aryl hydrocarbon receptor (AHR), target genes of transcription are necessary for understanding the normal developmental and pathological processes. Here, we examined the effects of human AHR ligands on male fecundity. To induce ectopic human gene expression, we used transformed with human under the control of a yeast promoter element capable of activation in the two-component system.

[Aryl-hydrocarbon receptor as a potential target for anticancer therapy].

Aryl-hydrocarbon receptor (Aryl Hydrocarbon Receptor, AHR) is a ligand-dependent transcription factor, whose functions are related to xenobiotic detoxification, response to inflammation, and maintenance of tissue homeostasis. Recent investigations suggest that AHR also plays an important role in the processes of carcinogenesis. Increased expression of AHR is observed in several types of tumors and tumor cell lines.

Xenobiotic-induced activation of human aryl hydrocarbon receptor target genes in is mediated by the epigenetic chromatin modifiers.

Aryl hydrocarbon receptor (AHR) is the key transcription factor that controls animal development and various adaptive processes. The AHR's target genes are involved in biodegradation of endogenous and exogenous toxins, regulation of immune response, organogenesis, and neurogenesis. Ligand binding is important for the activation of the AHR signaling pathway.

Combination of hypomorphic mutations of the Drosophila homologues of aryl hydrocarbon receptor and nucleosome assembly protein family genes disrupts morphogenesis, memory and detoxification.

Aryl hydrocarbon receptor is essential for biological responses to endogenous and exogenous toxins in mammals. Its Drosophila homolog spineless plays an important role in fly morphogenesis. We have previously shown that during morphogenesis spineless genetically interacts with CG5017 gene, which encodes a nucleosome assembly factor and may affect cognitive function of the fly.

[Gene expression modulation is an evolutionary resource of adaptive alterations in the morphogenesis of insect limbs].

Hypomorphic mutations have been investigated of the genes spineless (ss), Distal-less (Dll), leg-arista-wing complex/TBP-related factor 2(lawc/Trf2), CG5017, and hsp 70 in order to explore the effects of their expression level on the formation of distal structures of antenna and legs of Drosophila melanogaster. We demonstrated the effect of the CG5017, hsp 70, Dll, and lawc gene transcription level on phenotypic manifestation of the ss gene mutation and the involvement of these genes into morphogenesis regulation of Drosophila melanogaster limbs. The total decrease in the level of the CG5017, hsp 70, Dll, and laws gene expression level was shown to promote a loss of the segmented pattern of distal structures of legs and antennae and a reversion of Drosophila limb morphogenesis to the evolutionarily earlier progenitors of insects.

[Interaction of the ss and CG5017 genes in the regulation of morphogensis of limbs in Drosophila melanogaster].

The influence of the P-element built into the area of the CG5017 gene on the mutation of the spineless (ss) gene was studied. It was shown that the insertion of the P-element decreased the level of transcription of CG5017 approximately twofold. Modulation of the level of transcription of the CG5017 gene helped demonstrate, for the first time, its influence on the phenotypic manifestation of the mutation of the ss gene, which shows their interaction in the process of regulation of morphogenesis of limbs in Drosophila melanogaster.

[Nitric oxide synthase mediates regulation of cell polarity and movement during Drosophila melanogaster morphogenesis].

The effect of expression of the enzyme producing nitric oxide on Drosophila melanogaster morphogenesis was studied using ectopic expression of a truncated splice form of the enzyme that has a dominant negative effect on the full-length enzyme form. The suppressed enzyme expression was shown to affect the cell polarity and movement as well as the structural pattern of organs during Drosophila development. The effect of nitric oxide production on the intercellular distribution of significant factors of cell polarity, protein products of the Strabismus and Prospero genes, has been revealed.

[Regulation of multimeric structure of NO-synthase as a new factor of organogenesis].

The effect of NO on organogenesis in Drosophila is discussed. A new model of regulation of the activity of NO-producing enzyme, NO synthase is described, which takes into account endogenous synthesis of its reduced isoform. The reduced isoform of NO synthase is capable of suppressing the enzymatic activity of full-sized NO synthase during formation of a heterodimer in vivo and in vitro.

Nitric oxide is a regulator of hematopoietic stem cell activity.

Hematopoietic stem cells give rise to various multipotent progenitor populations, which expand in response to cytokines and which ultimately generate all of the elements of the blood. Here we show that it is possible to increase the number of stem and progenitor cells in the bone marrow (BM) by suppressing the activity of NO synthases (NOS). Exposure of mice to NOS inhibitors, either directly or after irradiation and BM transplantation, increases the number of stem cells in the BM.

Regulation of multimers via truncated isoforms: a novel mechanism to control nitric-oxide signaling.

Nitric oxide (NO) is an essential regulator of Drosophila development and physiology. We describe a novel mode of regulation of NO synthase (NOS) function that uses endogenously produced truncated protein isoforms of Drosophila NOS (DNOS). These isoforms inhibit NOS enzymatic activity in vitro and in vivo, reflecting their ability to form complexes with the full-length DNOS protein (DNOS1).

The Drosophila nitric-oxide synthase gene (dNOS) encodes a family of proteins that can modulate NOS activity by acting as dominant negative regulators.

Nitric oxide (NO) is involved in organ development, synaptogenesis, and response to hypoxia in Drosophila. We cloned and analyzed the only gene in the fly genome that encodes Drosophila nitric-oxide synthase (dNOS). It consists of 19 exons and is dispersed over 34 kilobases of genomic DNA.

Nitric oxide interacts with the retinoblastoma pathway to control eye development in Drosophila.

Animal organ development requires that tissue patterning and differentiation is tightly coordinated with cell multiplication and cell cycle progression. Several variations of the cell cycle program are used by Drosophila cells at different stages during development [1] [2]. In imaginal discs of developing larvae, cell cycle progression is controlled by a modified version of the well-characterized mammalian retinoblastoma (Rb) pathway [3] [4], which integrates signals from multiple effectors ranging from growth factors and receptors to small signaling molecules.

Nitric oxide and Drosophila development.

Mechanisms controlling the transition of precursor cells from proliferation to differentiation during organism development determine the distinct anatomical features of tissues and organs. NO may mediate such a transition since it can suppress DNA synthesis and cell proliferation. Inhibition of NOS activity in the imaginal discs of Drosophila larvae results in hypertrophy of tissues and organs of the adult fly, whereas ectopic overexpression of NOS has the reciprocal, hypotrophic, effect.

[The neurotropic effect of aplegin (carnitine) in cerebral hypoxia].

Intravenously injected aplegin (carnitine) competitively displacing glucose, includes metabolic shunt of fatty acids, the activity for which was determined by the presence of free carnitine and was not limited by oxygen unlike the aerobic glycolysis. This effect may have paramount importance in acute hypoxia of the brain, and in some other critical conditions. Carnitine has a potent neurotrophic activity.

[NO synthetase in the cells of different tissues and organs of the mouse].

Cellular NO synthase was assayed in bone marrow, spleen, thymus, lymph nodes, epidermis, hypodermic connective tissue, small gut, peritoneal exudate, liver, kidney, and heart by cytochemical and immunofluorescent methods. As a rule the enzymatic activity was found in differentiated cells that finished proliferation (mature hemopoietic cells, epithelium of gut villi, etc.).

Interaction between spineless-aristapedia gene and genes from Antennapedia and bithorax complexes of Drosophila melanogaster.

Mutations in the spineless-aristapedia (ssa) gene of Drosophila melanogaster are pleiotropic, and their classical manifestations include a reduction in size of all bristles (spineless phenotype), transformation of distal parts of antennae into tarsal segments of the mesothoracic leg (aristapedia phenotype), and, in extreme alleles, fusion of tarsal segments on all six legs and the transformed aristaes. We isolated a new allele, which is a severe loss-of-function mutation and, in addition to the above-mentioned features, is characterized by amplification of sex combs on the first leg. This phenotype can be caused by a change in the expression of the Sex combs reduced (Scr) gene of the ANTP-C.

Nitric oxide regulates cell proliferation during Drosophila development.

Cell division and subsequent programmed cell death in imaginal discs of Drosophila larvae determine the final size of organs and structures of the adult fly. We show here that nitric oxide (NO) is involved in controlling the size of body structures during Drosophila development. We have found that NO synthase (NOS) is expressed at high levels in developing imaginal discs.

The Drosophila trithorax gene encodes a chromosomal protein and directly regulates the region-specific homeotic gene fork head.

The activity of the Drosophila gene trithorax is required to maintain the proper spatial pattern of expression of multiple homeotic genes of the Bithorax and Antennapedia complexes, trithorax encodes two large protein isoforms of > 400 kD. We have detected its products at 16 discrete sites on larval salivary gland polytene chromosomes, 12 of which colocalize with binding sites of several Polycomb group proteins. The intensity of trithorax protein binding is strongly decreased in larvae carrying mutations in another trithorax group gene ash-1, and in the Polycomb group gene pco/E(z).

Regulation of tissue-specific expression of the esterase S gene in Drosophila virilis.

The esterase S gene (estS) of Drosophila virilis is specifically expressed in the ejaculatory bulbs of males. Its sequencing shows similarities between estS product and other esterases of different origin. The transcription of estS in ejaculatory bulbs is at least 2 orders of magnitude higher than in other tissues of males.

[A new allele variant of ssa and its participation in regulating the proliferation of the stem elements of the leg and antenna imaginal disks in Drosophila melanogaster].

Using a highly mutable FM/w oc system, we have established a new allele of ssa40aSc mutation whose phenotype is identical to ssa40aNs compound described in the literature. The following features are characteristic of the ssa40aSc flies phenotype: (1) the increased number of sex comb teeth, (2) complete fusion of tarsal segments, and (3) the decreased bristle size corresponding to that of ss flies. The first two features are evidence for the impaired stem cell proliferation in the antennal and leg imaginal discs which are determined to form distal structures.

[Injection of gene p53 into the pronuclei of mouse zygotes].

Attempts to transfer gene p53 via pAT153 vector to the mouse genome are described. Transgenic mice were obtained that carried sequences homologous to the pAT153 only. No transmission of foreign nucleotide sequences to progeny was observed.