Specific resistance to 8-azaguanine in cells with normal hypoxanthine phosphoribosyltransferase (HPRT) activity: the role of guanine deaminase

1981 ◽  
Vol 30 (2) ◽  
pp. 118-128 ◽  
Author(s):  
M.B. Meyers ◽  
S. Shin
Life ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 72
Author(s):  
Klaudia Staszak ◽  
Izabela Makałowska

This review summarizes the knowledge about retrogenes in the context of cancer and evolution. The retroposition, in which the processed mRNA from parental genes undergoes reverse transcription and the resulting cDNA is integrated back into the genome, results in additional copies of existing genes. Despite the initial misconception, retroposition-derived copies can become functional, and due to their role in the molecular evolution of genomes, they have been named the “seeds of evolution”. It is convincing that retrogenes, as important elements involved in the evolution of species, also take part in the evolution of neoplastic tumors at the cell and species levels. The occurrence of specific “resistance mechanisms” to neoplastic transformation in some species has been noted. This phenomenon has been related to additional gene copies, including retrogenes. In addition, the role of retrogenes in the evolution of tumors has been described. Retrogene expression correlates with the occurrence of specific cancer subtypes, their stages, and their response to therapy. Phylogenetic insights into retrogenes show that most cancer-related retrocopies arose in the lineage of primates, and the number of identified cancer-related retrogenes demonstrates that these duplicates are quite important players in human carcinogenesis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Min Choi ◽  
Seung Eun Baek ◽  
Ji On Kim ◽  
Eun Yeong Jeon ◽  
Eun Jeong Jang ◽  
...  

AbstractMonocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.


Author(s):  
Fulvio Reggiori ◽  
Hans-Joachim Gabius ◽  
Massimo Aureli ◽  
Winfried Römer ◽  
Sandro Sonnino ◽  
...  

AbstractGlycans have been shown to function as versatile molecular signals in cells. This prompted us to look at their roles in endocytosis, endolysosomal system and autophagy. We start by introducing the cell biological aspects of these pathways, the concept of the sugar code, and provide an overview on the role of glycans in the targeting of lysosomal proteins and in lysosomal functions. Moreover, we review evidence on the regulation of endocytosis and autophagy by glycans. Finally, we discuss the emerging concept that cytosolic exposure of luminal glycans, and their detection by endogenous lectins, provides a mechanism for the surveillance of the integrity of the endolysosomal compartments, and serves their eventual repair or disposal.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessia Oppezzo ◽  
Filippo Rosselli

AbstractHaematopoiesis, the process by which a restrained population of stem cells terminally differentiates into specific types of blood cells, depends on the tightly regulated temporospatial activity of several transcription factors (TFs). The deregulation of their activity or expression is a main cause of pathological haematopoiesis, leading to bone marrow failure (BMF), anaemia and leukaemia. TFs can be induced and/or activated by different stimuli, to which they respond by regulating the expression of genes and gene networks. Most TFs are highly pleiotropic; i.e., they are capable of influencing two or more apparently unrelated phenotypic traits, and the action of a single TF in a specific setting often depends on its interaction with other TFs and signalling pathway components. The microphthalmia-associated TF (MiTF) is a prototype TF in multiple situations. MiTF has been described extensively as a key regulator of melanocyte and melanoma development because it acts mainly as an oncogene. Mitf-mutated mice show a plethora of pleiotropic phenotypes, such as microphthalmia, deafness, abnormal pigmentation, retinal degeneration, reduced mast cell numbers and osteopetrosis, revealing a greater requirement for MiTF activity in cells and tissue. A growing amount of evidence has led to the delineation of key roles for MiTF in haematopoiesis and/or in cells of haematopoietic origin, including haematopoietic stem cells, mast cells, NK cells, basophiles, B cells and osteoclasts. This review summarizes several roles of MiTF in cells of the haematopoietic system and how MiTFs can impact BM development.


2021 ◽  
Author(s):  
Kanae Tsubotani ◽  
Sayuri Maeyama ◽  
Shigeru Murakami ◽  
Stephen W Schaffer ◽  
Takashi Ito

AbstractTaurine is a compatible osmolyte that infers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.


2020 ◽  
Vol 26 (3) ◽  
pp. 78-82
Author(s):  
Т. F. Golubova ◽  
А. I. Kreslov

Climate is an active, powerful factor that can have a powerful therapeutic effect. Climatotherapy is prescribed for the purpose of General strengthening effects on the body, to stimulate its defenses, increase non-specific resistance, especially in chronic or sluggish pathological processes. The effect of climate therapy is manifested in the body's responses to environmental factors, the main condition of which is the use of physiologically based methods of dosing climate procedures. The bioclimatic station (BCS) of the resort of Yevpatoria carries out meteorological observations of medical orientation and their dosing. The creation of a modern center of climatotherapy, as a scientific-clinical Department of medical climatology on the basis of the BCS will allow to organize a single service on introduction of modern methods of climatotherapy in Evpatoria and the Republic of Crimea, improve the quality of the holiday of climateprotection and effectiveness of climatotherapy.


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