卷 82, 编号 9 (2017)

Formation of appropriate gut microbiota is essential for human health. The first two years of life is the critical period for this process. Selection of mutualistic microorganisms of the intestinal microbiota is controlled by the FUT2 and FUT3 genes that encode fucosyltransferases, enzymes responsible for the synthesis of fucosylated glycan structures of mucins and milk oligosaccharides. In this review, the mechanisms of the selection and maintenance of intestinal microorganisms that involve fucosylated oligosaccharides of breast milk and mucins of the newborn’s intestine are described. Possible reasons for the use of fucose, and not sialic acid, as the major biological signal for the selection are also discussed.

The essential amino acid threonine is not synthesized in vertebrates, so it must be obtained from food. During evolution, the decomposition of threonine has changed. Because the decomposition of threonine catalyzed by threonine dehydratase is irreversible, in the present work attention is focused on threonine dehydrogenase to show the inability of this enzyme to synthesize threonine in a reaction that would be the reverse of the reaction of threonine decomposition. The reason why threonine dehydrogenase cannot be used for the biosynthesis of threonine in mammalian tissues is discussed. It is concluded that some quantity of threonine is involved in transamination.

Remote ischemic preconditioning of hind limbs (RIPC) is an effective method for preventing brain injury resulting from ischemia. However, in numerous studies RIPC has been used on the background of administered anesthetics, which also could exhibit neuroprotective properties. Therefore, investigation of the signaling pathways triggered by RIPC and the effect of anesthetics is important. In this study, we explored the effect of anesthetics (chloral hydrate and Zoletil) on the ability of RIPC to protect the brain from injury caused by ischemia and reperfusion. We found that RIPC without anesthesia resulted in statistically significant decrease in neurological deficit 24 h after ischemia, but did not affect the volume of brain injury. Administration of chloral hydrate or Zoletil one day prior to brain ischemia produced a preconditioning effect by their own, decreasing the degree of neurological deficit and lowering the volume of infarct with the use of Zoletil. The protective effects observed after RIPC with chloral hydrate or Zoletil were similar to those observed when only the respective anesthetic was used. RIPC was accompanied by significant increase in the level of brain proteins associated with the induction of ischemic tolerance such as pGSK-3β, BDNF, and HSP70. However, Zoletil did not affect the level of these proteins 24 h after injection, and chloral hydrate caused increase of only pGSK-3β. We conclude that RIPC, chloral hydrate, and Zoletil produce a significant neuroprotective effect, but the simultaneous use of anesthetics with RIPC does not enhance the degree of neuroprotection.

Changes in expression levels of genes encoding carbonic anhydrases α-CA1, α-CA2, α-CA4, β-CA1, β-CA2, βCA3, β-CA4, β-CA5, and β-CA6 in Arabidopsis thaliana leaves after light increase from 80 to 400 μmol PAR quanta·m−2·s−1 were investigated under short day (8 h) and long day (16 h) photoperiods. The expression of two forms of the gene, At3g01500.2 and At3g01500.3, encoding the most abundant carbonic anhydrase of leaves, β-CA1, situated in chloroplast stroma, was found. The content of At3g01500.3 transcripts was higher by approximately an order of magnitude compared to the content of At3g01500.2 transcripts. When plants were adapted to high light intensity under short day photoperiod, the expression level of both forms increased, whereas under long day photoperiod, the content of At3g01500.3 transcripts increased, and the content of transcripts of At3g01500.2 decreased. The expression levels of the At3g01500.3 gene and of genes encoding chloroplast carbonic anhydrases α-CA1, α-CA4, α-CA2 and cytoplasmic carbonic anhydrase β-CA2 increased significantly in response to increase in light intensity under short day, and these of the first three genes increased under long day as well. The expression level of the gene encoding α-CA2 under long day photoperiod as well as of genes of chloroplast β-CA5 and β-CA4 from plasma membranes and mitochondrial β-CA6 under both photoperiods depended insignificantly on light intensity. Hypotheses about the roles in higher plant metabolism of the studied carbonic anhydrases are discussed considering the effects of light intensity on expression levels of the correspondent genes.

Recent proteomic profiling of mouse brain preparations using the ubiquitin receptor, Rpn10 proteasome subunit, as an affinity ligand revealed a representative group of proteins bound to this sorbent (Medvedev, A. E., et al. (2017) Biochemistry (Moscow), 82, 330-339). In the present study, we investigated interaction of the Rpn10 subunit of proteasomes with some of these identified proteins: glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase, and histones H2A and H2B. The study revealed: (i) quantitative affinity interaction of the proteasome subunit immobilized on a Biacore-3000 optical biosensor cuvette with both the GAPDH (K_d = 2.4·10–6 M) and pyruvate kinase (K_d = 2.8·10^–5 M); (ii) quantitative high-affinity interaction of immobilized histones H2A and H2B with the Rpn10 subunit (Kd values of 6.5·10^–8 and 3.2·10^–9 M, respectively). Mass spectrometric analysis revealed the presence of the ubiquitin signature (GG) only in a highly purified preparation of GAPDH. We suggest that binding (especially high-affinity binding) of non-ubiquitinated proteins to the Rpn10 proteasome subunit can both regulate the functioning of this proteasomal ubiquitin receptor (by competing with ubiquitinated substrates) and promote activation of other pathways for proteolytic degradation of proteins destined to the proteasome.

The role of phosphatidylinositol-3 kinase (PI3K) and protein kinase A (PKA) in leptin and ghrelin regulation of formation of adaptive (a) subpopulations of CD4+ T-lymphocytes (helper (h) cells producing interleukin-17A) (aTh17) and of T-regulatory lymphocytes (aTreg) in the context of physiological pregnancy is established. It is shown that leptin at a concentration typical for the second half of pregnancy (trimesters II-III) enhances the differentiation of aTh17 with a high level of interleukin-17A (IL-17A) production and the expression of the chemokine receptor CCR6 with the participation of PI3K. Simultaneously, leptin reduces formation of aTreg expressing the suppressor molecule CTLA-4, which determines the function of these cells. Ghrelin at a concentration characteristic of the first half of pregnancy (trimesters I-II), in contrast, enhances aTreg formation and, in parallel, reduces the level aTh17 (that express CCR6) and the IL-17A production by aTh17. PKA, likewise PI3K, participates in regulatory effects of ghrelin on the formation of aTh17 and aTreg. The combined action of leptin and ghrelin (via PKA participation) enhances formation of only aTreg, which determines the priority of this molecular mechanism and explains why the investigated hormones with reciprocal differentiating potential do not come into antagonism at the level of immune system cells during pregnancy.