Why Cancer?
John Melford in Pocket Guide to Cancer, 2017
A certain person has given genes a bad name by describing them as selfish. What does that make cancer? The persistence of genes that provide a survival advantage is eloquently demonstrated by the genetically inherited condition of sickle-cell anemia. Hemoglobin is a protein that carries oxygen around in the blood. It is made up of four protein molecules, two α-chains and two β-chains that cluster together to form a complex. Sufferers of sickle-cell anemia inherit faulty β-chain genes from both parents that impact the formation of the full hemoglobin complex. Instead of the four chains coming together to form a globular shape that is soluble, a long fibrous shape is formed that is not soluble. This happens because a gene mutation that brings about the substitution of a single amino acid on the β-chain of hemoglobin creates a sticky patch that causes it to aggregate, the effects of which are:
Carbon Monoxide Poisoning, Methemoglobinemia, and Sulfhemoglobinemia
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Oxygen transport to the tissues, the ultimate purpose of hemoglobin, is dependent on blood flow, which in turn is affected by cardiac output and by microcirculatory size and distribution, the Hb concentration, and O2 extraction by the tissues, which in turn is dependent on the shape of the oxygen-binding curve of the red cells and on tissue pO2. The shape of the oxygen equilibrium curve in Hb is sigmoidal. This shape is determined by the extent of cooperativity: The initial portion of the curve has a very low slope, reflecting a low affinity for oxygen by hemoglobin at the beginning of the loading process. In other words, when Hb is totally deoxygenated, it has a rather poor avidity for oxygen (Fig. 3). As the loading proceeds, and as the molecule binds more oxygen molecules, the slope of the reaction begins to change rapidly and becomes steep. This means that the affinity for oxygen has become much higher in spite of the sluggish beginning. In other words, the initial molecules of oxygen that bind a deoxy-Hb tetramer change this protein avidity for oxygen. This property assures that hemoglobin tetramers, once they begin to accept oxygen, will be fully oxygenated promptly.
Genetic Control of Host Resistance to Malaria
Mary M. Stevenson in Malaria: Host Responses to Infection, 2017
Because the intraerythrocytic multiplication of parasites of the Plasmodium species results in the symptomatology and pathology associated with malaria, inability of the parasite to develop normally once it invades the cell will result in less severe infections. In 1954, Allison14 suggested an association between the high incidence of the trait for sickle cell hemoglobin and resistance to falciparum malaria in areas of Africa where this form of malaria is epidemic. Later studies showed that individuals with the sickle cell trait, either in the homozygous or heterozygous form (i.e., genotypically either SS or AS), and those with the trait of normal hemoglobin (AA) had the same incidence of infection but the severity of the disease differed.15,16 The basis of less severe malaria in individuals with SS or AS hemoglobin appears to be due to the inability of the parasite to develop normally at low oxygen tensions which cause the cell to sickle.17 It has also been observed that invasion of cells containing hemoglobin S is prevented under low oxygen tensions;18 thus, the presence of hemoglobin S appears to limit both the invasion by P. falciparum and its development within erythrocytes under conditions of reduced oxygen to which parasitized red cells are exposed, particularly in the spleen.19
Krüppel-Like Factor 1 Gene Mutations in Thalassemia Patients from North Iran: Report of a New Mutation Associated with β-Thalassemia Intermedia
Published in Hemoglobin, 2019
Ahmad Tamaddoni, Sahar Khabaz Astaneh, Reza Tabaripour, Haleh Akhavan-Niaki
Thalassemia is an inherited blood disorder characterized by decreased Hb production. Hemoglobin is the major protein of red blood cells (RBCs) and carries oxygen. The thalassemia disorder results in excessive destruction of RBCs, which leads to anemia. Numerous interacting environmental and genetic factors such as modifier genes exert their influence on globin gene expression [14]. The KLF1 gene acts as an important erythroid-specific transcription factor that regulates the development of erythrocytes [20]. It functions as a regulator of fetal-to-adult globin change in the process of erythropoiesis. By binding to the β-globin gene promoter, KLF1 participates in HBB gene transcription activation. Moreover, it binds to the promoter of the BCL11A gene, and activates its expression, which in turn suppresses HBG1 and HBG2 gene expressions leading to γ-globin chain synthesis down-regulation. The γ chains along with α chains make up Hb F. By these two mechanisms, KLF1 decreases Hb F levels in adults [2,20–24]. KLF1 also has a role in histone modification, and modulates chromatin structure and facilitates TAL-1 and GATA-1 occupancy in the β-globin locus. Investigations indicated that reduced expression of KLF1 in erythroid K562 cells cause the decrease of γ-globin transcription with the loss of active chromatin structure and reduction in binding of GATA-1 and TAL-1 in the β-globin locus [25].
Evaluation of the Function of a Rare Variant in the 3'-Untranslated Region of the β-Globin Gene
Published in Hemoglobin, 2022
Sogol Targholi, Zahra Noormohammadi, Elham Tafsiri, Morteza Karimipoor
Hemoglobin (Hb) is a protein in red blood cells (RBCs) that carry oxygen to tissues and comprise two pairs of α and β chains. During development from embryonic to adulthood, the composition of globin chains in the structure of Hb changes. The β-globin gene cluster is located on chromosome 11p15.5. In this cluster, in addition to the β-globin gene, ε, Aγ and Gγ, and δ genes are located. These genes are expressed at different stages of development. β-Thalassemia (β-thal) is one of the most common genetic disorders caused by the absence or reduced synthesis of the β-globin chain. It is most common in the Mediterranean regions, some parts of North and West Africa, the Middle East and the Indian subcontinent, the Far East, and Southeast Asia (known as the thalassemia belt). The prevalence of the disease is low in Western countries, for example, in the United States, there are only about a thousand patients with β-thal major (β-TM). Additionally, most of the carriers and patients living in Western countries are immigrants [1–4].
The effect of natural biomolecules on yttrium oxide nanoparticles from a Daphnia magna survival rate perspective
Published in Nanotoxicology, 2023
Egle Kelpsiene, Tingru Chang, Alexander Khort, Katja Bernfur, Inger Odnevall, Tommy Cedervall, Jing Hua
Vitellogenin-1 has previously been identified as one of the general proteins that bind to NPs after incubation with D. magna. Examples of such NPs include Au NPs (Mattsson et al. 2018), differently surface-charged polystyrene NPs (Kelpsiene et al. 2022), and Ag NPs (Gao et al. 2017). Vitellogenin-1 plays an important role in oogenesis and is highly expressed in females (Hara, Hiramatsu, and Fujita 2016, Gao et al. 2017). Hemoglobin is a polyfunctional molecule that is mainly involved in oxygen binding and transport (Ahmed, Ghatge, and Safo 2020). Serine protease has also been identified to extensively interact with 53 nm sized PS-NH2 NPs and to some extent with 200 nm sized PS-NH2 NPs (Kelpsiene et al. 2022). Our previous findings show that actin, alpha skeletal muscle commonly binds to both negatively and positively charged polystyrene NPs after incubation with D. magna (Kelpsiene et al. 2022). Actin protein plays an important role in the structure and motio of cells. Changes of its expression can lead to toxicity (Gunning et al. 2015). The presence of heat shock 70 kDa protein cognate is in line with previous findings where the protein was reported to be secreted by D. magna in response to metallic NPs (Ellis and Lynch 2020) and to 53 nm sized PS-NH2 NPs (Kelpsiene et al. 2022). Results of this study show lamin-A to only be detected in the 20–40 nm sized Y2O3 NPs sample, the same protein also shown to interact only with the 200 nm sized PS-NH2 NPs (Kelpsiene et al. 2022).
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