Activation of the aryl hydrocarbon receptor (AhR), a conserved transcription factor best known as a target for highly toxic halogenated substances such as dioxin, under normal xenobiotic-free conditions is of considerable scientific interest. We have demonstrated previously that a photoproduct of tryptophan, 6-formylindolo[3,2-b]carbazole (FICZ), fulfills the criteria for an endogenous ligand for this receptor and proposed that this compound is the enigmatic mediator of the physiological functions of AhR. Here, we describe novel light-independent pathways by which FICZ can be formed. The oxidant H2O2 was shown to convert tryptophan to FICZ on its own in the absence of light. The enzymatic deamination of tryptamine yielded indole-3-acetaldehyde (I3A), which then rearranged to FICZ and its oxidation product, indolo[3,2-b]carbazole-6-carboxylic acid (CICZ). Indole-3-pyruvate (I3P) also produced I3A, FICZ, and CICZ. Malassezia yeast species, which constitute a part of the normal skin microbiota, produce a number of AhR activators from tryptophan. We identified both FICZ and CICZ among those products. Formation of FICZ from tryptophan or I3P produces a complex mixture of indole derivatives, some of which are CYP1A1 inhibitors. These can hinder the cellular clearance of FICZ and thereby increase its power as an AhR agonist. We present a general molecular mechanism involving dehydrogenations and oxidative coupling for the formation of FICZ in which I3A is the important precursor. In conclusion, our results suggest that FICZ is likely to be formed systemically.
Abstract.
1The data on the viscosity of the tar when dissolving non-substituted aromatic compounds (naphthalene and anthracene) were received. The viscosity coefficients of available empirical equations when adding the naphthalene and anthracene were determined. The rheological properties of the tar on a Brookfield viscometer were investigated with imitative additives. Irregular values of energy activation of viscous flow were established with the additive of certain amount of naphthalene that also correlated with the minimum value of the constant K2 of Walter equation and constant В in the equation of CornelissenWaterman. The above data allow to recommend the temperature ranges and optimal amount of naphthalene for obtaining coal tar with improved rheological properties.
Формирование адаптивного поведения ребенка происходит под влиянием процессов семейного взаимодействия и детерминировано семейной структурой, родительским копинг-стилем, полоролевыми стереотипами воспитания, а также характером детско-родительских отношений. Ребенок не копирует паттерн копинг-поведения родителя, а вынужден адаптироваться к нему в зависимости от того, как реально выстраиваются его отношения с взрослым и какими он их «видит».
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