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Basic Cell Biology
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Ribosomes (also referred to as ribonucleoprotein or microsomes) from widely different organisms are remarkably uniform in their general properties.17 These particles are composed of 40% protein and 60% RNA, and they constitute 80–90% of cellular RNA. Ribosomes are metabolically stable and occur in the cell either as a free form (70 S) or as subunits (50S and 30 S). During the process of protein synthesis, more than one ribosome is present on the messenger RNA (mRNA) strand, and ribosome-mRNA complexes are referred to as polysomes.
Physiology and Growth
Published in Paul Pumpens, Single-Stranded RNA Phages, 2020
Concerning protein synthesis in E. coli cells, both total and β-galactosidase synthesis were gradually reduced during the progress of the MS2 infection, whereas synthesis of the viral coat protein increased gradually until it accounted for 30%–40% of the total protein synthesized in the cell (Sugiyama and Stone 1968a,b). The distribution of polysomes obtained from the R17-infected cells shifted toward smaller polysomes as early as 10 minutes after infection (Hotham-Iglewski and Franklin 1967). The inhibition of the inducible β-galactosidase synthesis, although not complete, was apparent shortly after infection of E. coli with the phage R23 and was maximal after the first 20 min of infection (Watanabe and Watanabe 1968; Watanabe M et al. 1968). The primary effect of this phenomenon was explained by limitation of synthesis of enzyme-specific mRNA, whereas the inhibitory process was separated into two phases: early inhibition, which did not require the expression of the viral genome, and late inhibition, which required the expression of the viral RNA replicase gene (Watanabe and Watanabe 1968, 1970c).
Cellular Responses to Ischaemic CNS Injury
Published in Martin Berry, Ann Logan, CNS Injuries: Cellular Responses and Pharmacological Strategies, 2019
In the “light/pale” response there is the impression of an increase in cell size with clustering of organelles around the crenated nucleus, resulting in a lucency of the peripheral cytoplasm in which cytoplasmic organelles are scarce (Figure 2.6). In these cells there is also an increase in the size of the nucleolus. The “light” cells remain in some numbers scattered among intact or normal neurons in long-term survival, up to 10 months, after cardiac arrest. In these cells the nuclear chromatin is finely aggregated, the nuclear envelope is intact, and crenations are absent. The cytoplasm contains aggregates of lipofuscin granules and lysosomes. Ribosomes form aggregates or polysomes. The peripheral rim of the cytoplasm is void, providing the “pale” appearance of these cells.59 Although the present evidence is still largely anecdotal, there is now consensus in the literature that these “dark” and “pale” changes reflect the incidence of two discrete pathologies in neurons after an ischaemic insult. “Dark” neurons do not occur between 6 and 10 months after transient cardiac arrest,59 while “pale” cells are still numerous, occurring among morphologically intact cells. This has led to the suggestion that morphological changes in “pale” neurons, including both pyramidal and interneurons, are reversible59 and allow recovery after ischaemia.
The effects of transpositions of functional I retrotransposons depend on the conditions and dose of parental exposure
Published in International Journal of Radiation Biology, 2023
Based on the negative effect of maternal irradiation on survival, the cellular systems of controlling TEs can decrease and retrotransposons can become more active which ultimately leads to acceleration of the aging process under taken irradiation conditions. Under the influence of environmental stress factors, mRNA and proteins of retrotransposons can accumulate in stress granules (ribonucleoprotein complexes). They are formed due to stress-induced phosphorylation of the eukaryotic initiating factor (eIF), which inhibits the translation of mRNA. Then, mRNA leaves the polysome and interacts with Piwi proteins to form stress granules (Kedersha and Anderson 2002). This method of Piwi protein deposition prevents the silencing of RNA transcription of retrotransposons and causes their subsequent accumulation in somatic cells, leading to age-dependent changes and a decrease in lifespan (Hwang et al. 2019).
Streptogramins for the treatment of infections caused by Gram-positive pathogens
Published in Expert Review of Anti-infective Therapy, 2021
Sophie Reissier, Vincent Cattoir
Type A streptogramins block tRNAs attachment to both A and P sites of the peptidyl-transferase center (PTC), and thus preventing the two early steps of elongation (i.e. aminoacyl-tRNA binding to the A site and peptide bond formation with peptidyl-tRNA at the P site) Figure 2 [21,22]. Initially, it was thought that streptogramins A were only able to bind to 50S subunits and free 70S ribosomes and not to ribosomes involved in protein synthesis and polysomes [22]. However, it has been demonstrated that streptogramins A also interact with the entrance of the peptide exit tunnel, and likely bind to translating ribosomes [25]. Type B streptogramins share overlapping binding sites with macrolides and lincosamides (domains II and V of the 23S rRNA), and act similarly by inhibiting translocation, preventing polypeptide extension, and triggering the premature release of incomplete protein chains [21,22]. Streptogramins B binding site is located at the entrance to the ribosome tunnel, and does not contact the PTC Figure 2 [26]. They can interact with ribosomes at any step of protein synthesis, including translating ribosomes and polysomes, inhibiting elongation after a few cycles [22].
The efficacy and safety of a homoharringtonine-based protocol for children with acute myeloid leukemia: A retrospective study in China
Published in Pediatric Hematology and Oncology, 2020
Yanjing Tang, Chengjuan Luo, Shuhong Shen, Huiliang Xue, Ci Pan, Wenting Hu, Xiaoxiao Chen, Jiaoyang Cai, Jing Chen, Jingyan Tang
Homoharringtonine (HHT), a Chinese medicine extracted from Cephalotaxus species, has been widely used to treat adult AML and chronic myeloid leukemia in China since the 1970s.6–8 As a cell cycle-specific agent, it can achieve anti-tumor effects through the inhibition of protein synthesis, depolymerization of polysomes, and interference of ribosomal function. HHT can inhibit cell proliferation by obstructing the synthesis of DNA and RNA, and then inducing differentiation and apoptosis of tumor cells.9–11 Moreover, HHT might affect signaling pathways by regulating protein tyrosine kinase phosphorylation.12 Studies have shown that HHT has synergistic effects with cytarabine, leading to better curative effects with low cardiotoxicity in the treatment of adult AML patients in China.13 The previous clinical study XH-AML-99 for childhood AML, with HHT as one of the therapeutic agents, also proved to be effective with a 5-year EFS reaching 52.75% based on the data from the Shanghai Children’s Medical Center of China (SCMC).14 Therefore, we developed the AML-SCMC-2009 protocol to further investigate whether replacing most of anthracycline with HHT can also achieve good results while reducing adverse effects in children.