Inhibition of tumor growth in mice treated with synthetic muramyl dipeptide

Summary Treatment with synthetic MDP inhibited growth of transplantable, chemically induced tumors in syngeneic mice. The tumor-inhibitory effect was dependent on the schedule of MDP administration.Growth of SC transplants of a nonmetastasizing, MC-induced fibrosarcoma, MC11, was inhibited by local treatment with 200 g and 1,000 g MDP given SC 5–7 weeks before challenge. Treatment with lower (10 g and 100 g) doses of MDP and shorter (1–4 weeks) time intervals was not effective. Single doses of MDP (10–1,000 g) 1–3 weeks after challenge had no effect.Growth of IV-inoculated, metastasizing AAT-induced hepatoma A was inhibited by IV injections of 20 g MDP given 1 and 2 days prior to the challenge. Significant increases in the survival of hepatoma-bearing mice were observed only after injections of MDP incorporated in multilamellar liposomes.Abbreviations MDP n-acetylmuramyl-l-alanyl-d-isoglutamine - B10 C57BL/10ScSnPh mice - MC 3-methylcholanthrene - ATT o-amino-azotoluene - PBS phosphate-buffered saline     

Ubiquitous downregulation of InR gene expression affects stress associated hormone metabolism in Drosophila females

The effect of the ubiquitous downregulation of insulin receptor (InR) gene expression on the metabolism of juvenile hormone (JH) and dopamine (DA) in young females of D. melanogaster under normal conditions and heat stress is studied. The level of JH degradation and alkaline phosphatase activity (ALP, an enzyme regulating DA synthesis) were used as indicators of JH and DA levels, respectively. We demonstrated that, under normal conditions, the ubiquitous inhibition of the InR gene expression in D. melanogaster females induced an increase in the JH degradation and ALP activity. As we have already shown, this is indicative of the decrease in the concentration of the above hormones. It was also found that the total inactivation of InR does not affect the initiation of JH and DA metabolic system response to heat stress; however, it does affect its intensity. Thus, the involvement of the insulin signaling pathway in the regulation of the JH and DA metabolism in Drosophila females was demonstrated in vivo under normal and stress conditions.     

Mutation in the <Emphasis Type="Italic">Drosophila</Emphasis> insulin-like receptor substrate, <Emphasis Type="Italic">chico</Emphasis>, affects the neuroendocrine stress-reaction development

It is shown for the first time that the insulin receptor substrate gene chico controls the functioning of the systems of metabolism of dopamine and juvenile hormone in Drosophila melanogaster females under normal conditions and in thermal stress.     

Gene <Emphasis Type="Italic">dilp6</Emphasis> regulates octopamine metabolism in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The effect of strong hypomorphic mutation of the insulin-like protein gene (dilp6) on metabolism of octopamine (one of the main biogenic amines in insects) was studied in Drosophila melanogaster males and females. The activity of tyrosine decarboxylase (the key enzyme of octopamine synthesis) and the activity of octopamine-dependent N-acetyltransferase (the enzyme of its degradation) were measured. It was demonstrated that the activity of both studied enzymes is decreased under normal conditions in the dilp6⁴¹ mutants (as we previously demonstrated, this is correlated with an increased level of octopamine). It was also found that hypomorphic mutation of the dilp6 gene decreases the intensity of tyrosine decarboxylase response to heat stress. Thus, it was demonstrated for the first time that insulin-like DILP6 protein in drosophila influences the level of octopamine (regulating the activity of the enzyme degrading octopamine).     

The dopamine system stress reaction in adults of Drosophila virilis is controlled by genes of Chromosome 6

A linkage group of the gene responsible for changes of DA titer under stress in adults of D. virilis was determined. Line 160 of D. virilis, all autosomes of which bear visible recessive mutations, was used as an analyzer. Flies of lines 160 and 147 were shown to differ in DA content under normal conditions and in the way DA metabolic system reacts to stress. Among the offspring of the analyzing cross, groups of flies were found with one testable autosome from line 147 and all other chromosomes from line 160. Results of the DA titer measurements in flies of these groups under stress conditions have proved that the gene in question is linked to chromosome 6.     

Stress response in Drosophila melanogaster strain inactive with decreased tyramine and octopamine contents

Juvenile hormone hydrolysis, tyrosine decarboxylase activity, dopamine content and fitness (viability and fertility) were studied under normal and stress conditions in the adults of Drosophila melanogaster inactive strain carrying a mutation that decreases tyrosine decarboxylase activity and results in the lower contents of tyramine and octopamine. A sexual dimorphism of tyrosine decarboxylase activity, dopamine level and survival under heat stress in inactive flies was found. inactive adults showed higher dopamine levels and lower survival levels under heat stress as compared to wild type (Canton S) adults. Juvenile hormone degradation is decreased in young and increased in mature inactive females as compared to wild type. Fertility of the inactive strain did not differ from that of wild type strain under normal conditions, but after heat exposure the dynamics of its restoration was different. inactive females were found to develop the stress reaction, with juvenile hormone degradation, tyrosine decarboxylase activity, dopamine content and fertility levels used as the reaction indicators.     

Effects of octopamine on reproduction, juvenile hormone metabolism, dopamine, and 20-hydroxyecdysone contents in Drosophila

The effect of an experimentally increased octopamine content (feeding flies with OA) on the levels of juvenile hormone (JH) degradation, dopamine (DA), and 20-hydroxyecdysone (20E) contents, oogenesis, and fecundity of wild type Drosophila flies has been studied. OA feeding of the flies was found to (1) cause a considerable decrease in JH degradation in females, but not males, of D. melanogaster and D. virilis; (2) have no effect on DA content in D. melanogaster and D. virilis; (3) increase 20E contents in D. virilis females; (4) decrease to a large extent the number of vitellogenic (stages 8-10) and mature (stage 14) oocytes in D. virilis; and (5) decrease the fecundity of D. melanogaster and D. virilis. A possible mechanism of action of OA as a neurohormone on the reproductive function of Drosophila is discussed.     

Physiological Aspects of Wolbachia pipientis–Drosophila melanogaster Relationship

Journal of Evolutionary Biochemistry and Physiology - The intracellular bacterium Wolbachia pipientis is one of the most common prokaryotic symbionts of invertebrates. It is able to affect host...     

The <Emphasis Type="Italic">ecdysoneless</Emphasis><Superscript>1</Superscript> Gene Regulates Metabolism of the Juvenile Hormone and Dopamine in <Emphasis Type="Italic">Drosophila melanogaster</Emphasis>

The dopamine (DA) content and the level of juvenile hormone (JH) degradation were studied in females of the wild-type Canton S strain and the ecdysoneless ¹ (ecd ¹) mutant, which does not produce ecdysone at a restrictive temperature (29°C). Exposure at the restrictive temperature considerably increased the JH-hydrolyzing activity and the DA content in five-day ecd ¹ females compared with flies of both strains growing at 19°C and Canton S females exposed at 29°C. In one-day ecd ¹ females, the level of JH degradation also increased at the restrictive temperature, but the DA content was low. The effect of ecdysone deficiency on the stress reaction in Drosophila melanogaster females was studied using changes in DA content and JH degradation as the reaction indicators. The ecd ¹ mutation did not prevent the initiation of the stress reaction in females exposed at the restrictive temperature, but changed its intensity (stress reactivity). The interaction of 20-hydroxyecdysone with JH and DA in regulating Drosophila reproduction under normal conditions and in stress is discussed.