Cancer stem cells are a small subset of cancer cells constituting a reservoir of self-sustaining cells with the exclusive ability to self-renew and maintain the tumor. These cells are identified by specific stem cell markers: antigens, molecules and signaling pathways. Transcription factors and molecules associated with oncogenesis, such as NF-κB, Bmi-1, Notch, WNT beta-catenin, Sonic hedgehog and their biochemical pathways, active only in a small minority of cancer cells might play key roles in determining the biology and the overall long-term behavior of a tumor. The molecules and pathways specific for cancer stem cells, which contribute to their drug resistance, are potential targets for new therapeutic strategies.
The 6-oxopurine xanthine (Xan, neutral form 2,6-diketopurine) differs from the corresponding 6-oxopurines guanine (Gua) and hypoxanthine (Hyp) in that, at physiological pH, it consists of a ≈ 1:1 equilibrium mixture of the neutral and monoanionic forms, the latter due to ionization of N(3)-H, in striking contrast to dissociation of the N(1)-H in both Gua and Hyp at higher pH. In xanthosine (Xao) and its nucleotides the xanthine ring is predominantly, or exclusively, a similar monoanion at physiological pH. The foregoing has, somewhat surprisingly, been widely overlooked in studies on the properties of these compounds in various enzyme systems and metabolic pathways, including, amongst others, xanthine oxidase, purine phosphoribosyltransferases, IMP dehydrogenases, purine nucleoside phosphorylases, nucleoside hydrolases, the enzymes involved in the biosynthesis of caffeine, the development of xanthine nucleotide-directed G proteins, the pharmacological properties of alkylxanthines. We here review the acid/base properties of xanthine, its nucleosides and nucleotides, their N-alkyl derivatives and other analogues, and their relevance to studies on the foregoing. Included also is a survey of the pH-dependent helical forms of polyxanthylic acid, poly(X), its ability to form helical complexes with a broad range of other synthetic homopolynucleotides, the base pairing properties of xanthine in synthetic oligonucleotides, and in damaged DNA, as well as enzymes involved in circumventing the existence of xanthine in natural DNA.
W ostatnich latach nową, dynamicznie rozwijającą się gałęzią nauki o odporności jest immunometabolizm. Dział ten bada jak przemiany metaboliczne zachodzące w komórkach układu odpornościowego, wpływają na ich przetrwanie, rozwój, ale także funkcje wykonawcze. W opracowaniu tym opisujemy przebieg podstawowych i pomocniczych szlaków pozyskania energii przez leukocyty, a w szczególności glikolizę, cykl Krebsa, szlak pentozofosforanowy oraz utlenienie kwasów tłuszczowych. Przedstawiamy znaczenie poszczególnych szlaków dla funkcjonowania leukocytów, rozwoju ich fenotypu (np. makrofagów M1 i M2), oraz przełączania szlaków podczas ich aktywacji. Zmiany te mogą wpływać na funkcje obronne w czasie reakcji zapalnej, infekcji lub uszkodzenia tkanek. Z drugiej strony, leukocyty mogą realizować różne programy metaboliczne, celem pozyskania energii do walki z patogenami. Zależność pomiędzy funkcjami obronnymi a metabolizmem rzuca także nowe światło na zrozumienie mechanizmów chorób metabolicznych, a przede wszystkim kompleksowej odpowiedzi immunologicznej.
EN
In recent years, a new branch of immunology called immunometabolism has been established. The discipline focuses on intracellular metabolic changes in immune cells that impact - influence their survival, development, as well as defense mechanisms. Here we provide a brief summary of basic and ancillary metabolic pathways which leukocytes utilize to obtain energy, with a special focus on glycolysis, TCA cycle, penthosophosphate pathway and fatty acid oxidation. Significance of the given metabolic path for leukocyte functioning, phenotype changes (e.g. M1 vs. M2 macrophages) and biochemical changes during activation is discussed. The metabolic changes can in fact shape the effector functions during inflammation, infection or tissue injury. On the other hand, leukocytes can adopt different metabolic programs to gain energy required to eliminate pathogens. An interplay between immunity and metabolism sheds new light on understanding of metabolic diseases but foremost on complex immune responses.
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