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Evolutionary Biology of Parasitism
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The demands imposed on the same parasite in different hosts can have some interesting consequences, as pointed out by the following artificial situation. Some strains of the rodent parasite Plasmodium berghei that are routinely passaged by syringe (and not mosquitoes) to new hosts are resistant to the antimalarial compound atovaquone, conferring on them an ability to survive exposure to this drug when in the blood of mice. The basis for resistance lies in mutations in the cytochrome b gene (cytB) of the mitochondrion. These mitochondria nonetheless retain a low but necessary activity for bloodstream parasites. However, if these parasites are allowed to be transmitted by mosquitoes in which demands for oxidative respiration for P. berghei are much higher, the atovaquone-resistant mutants perish because of their mutated cytochrome b proteins. One lesson here is that if resistance to atovaquone facilitated by cytochrome b mutants were to arise in a human host, the mutant parasites would likely die in the mosquito vector, thus slowing or altogether preventing the spread of cytB-based atovaquone resistance.
A Pharmacological Appraisal of Antimalarial Plant Species
Published in Namrita Lall, Medicinal Plants for Cosmetics, Health and Diseases, 2022
Mahwahwatse J. Bapela, Precious B. Ramontja, Mcebisi J. Mabuza
Antifolates include two classes of antimalarial drugs that interfere with folate metabolism, a pathway essential for DNA replication and protein synthesis of malaria parasites. They specifically target two enzymes involved in the biosynthesis of tetrahydrofolate, the dihydropteroate synthase (DHPS) and dihydrofolate reductase (DHFR) (Rudrapal, 2011). Sulphonamides, sulphadoxine (Figure 18.3), sulphones, dapsone and sulphalene act as competitive inhibitors against DHPS, thereby preventing the formation of dihydropteroate. The second class includes proguanil, chloroproguanil, cycloguanil and pyrimethamine, which inhibit DHFR, consequently preventing the reduction of dihydrofolate (DHF) to tetrahydrofolic acid (THF). The combination of both classes of antifolates proved to have a synergistic effect against malaria, though clinical resistance developed quickly, compromising their use in many malaria-endemic areas (Heinberg and Kirkman, 2015). Atovaquone (Figure 18.3) is a hydroxynaphthoquinone that is used in combination with proguanil for prophylaxis and therapy of asymptomatic malaria. It is active against all Plasmodium species, inhibiting the exoerythrocytic stage in humans and the oocyst development in the mosquitoes. It acts by inhibiting the mitochondrial electron transport chain, thereby leading to a breakdown of the mitochondrial membrane potential (Barton et al., 2010). The prevalence of mutations of the cytochrome b gene has resulted in therapy failure of atovaquone (Siregar et al., 2015).
The Genetic Basis of NEC Susceptibility
Published in David J. Hackam, Necrotizing Enterocolitis, 2021
Lovya George, Wei Yu, Alain Cuna, Venkatesh Sampath
Gut ischemia followed by reperfusion produces reactive oxygen species (Figure 47.1). Oxidative stress coupled with immature antioxidant defenses can contribute to inflammation and tissue injury. Whether red cell transfusion confers increased risk of NEC, referred to as TANEC (transfusion associated NEC), is a matter of debate, but a recent meta-analysis suggests no increased risk (70, 71). Data from a large multicenter study by Patel et al. (72) suggest that severe anemia, and not transfusion, increases the risk for NEC. It has been suggested that TANEC might be the result of a two-hit process where red blood cell (RBC) transfusion on the background of an immature gut, prone to inflammation, generates an exaggerated immune response resulting in mucosal injury (73). Genetic variants that limit antioxidant defenses can hypothetically increase the risk of NEC (74). Sampath et al. (75) investigated loss-of-function SNPs in six antioxidant genes belonging to the NF-E2-related factor 2-dependent antioxidant response elements (Nrf2-ARE) pathway but found no evidence of association between the tested SNPs and NEC. Huizing et al. (76) looked at the C242T polymorphism of cytochrome B-245 alpha chain (a gene related to NADPH oxidase family) and found no association of this variant with NEC.
Catalpol promotes mitochondrial biogenesis in chondrocytes
Published in Archives of Physiology and Biochemistry, 2022
Dan Chen, Jing Guo, Longguang Li
Since the nuclear DNA level is relatively stable, we concluded that a 30 μM catalpol treatment for 48 h increased more than half of the mitochondrial mass. We then measured the expression of five mitochondrial importing proteins encoding genes including translocase of outer mitochondrial membrane 22 (Tomm22), translocase of outer mitochondrial membrane 70 (Tomm70), mitochondrial import inner membrane translocase subunit 50 (Timm50), NADH dehydrogenase [ubiquinone] iron-sulphur protein 3 (NDUFS3), and ATP synthase subunit D (ATP5d) by the PCR method. It showed that the same dose and time of catalpol treatment increased twofold expression of all these genes. Third, we measured the expression of mitochondrial protein cytochrome B and the result again confirmed that catalpol increased the expression of cytochrome B (Figure 3(C)) by 1.7-fold high. These experiments indicate that catalpol promotes mitochondrial biogenesis in chondrocytes.
Strobilurin fungicide kresoxim-methyl effects on a cancerous neural cell line: oxidant/antioxidant responses and in vitro migration
Published in Toxicology Mechanisms and Methods, 2018
Evangelia Flampouri, Dimitra Theodosi-Palimeri, Spyridon Kintzios
Strobilurins, a class of systemic fungicides, are among the best-selling agricultural fungicides worldwide and are used primarily as plant protectants against most major fungal and oomycete pathogens (Fernndez-ortuo et al. 2010). First appeared towards the end of the 1990s, their synthesis was based on the natural compounds of the saprotrophic wood-rotting fungi, Oudemansiella mucida and Strobirullus tenacellus and their mode of action results from the inhibition of mitochondrial respiration. They act through binding to the quinol oxidation (Qo) (ubiquinol) site of cytochrome b (complex III) in the mitochondria and thereby interfere with electron transfer between cytochrome b and cytochrome c, obstructing reduced nicotinamide adenine dinucleotide (NADH) oxidation and adenosine triphosphate (ATP) synthesis (Sauter et al. 1999).
Montelukast promotes mitochondrial biogenesis via CREB/PGC-1α in human bronchial epithelial cells
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2019
Huan Wang, Yali Cheng, Ying Liu, Jiang Shi, Zhe Cheng
To assess the effects of montelukast in mitochondrial biogenesis, mitochondrial mass of Beas-2b cells was examined using MitoTracker red staining. As shown in Figure 3(A), 10 µM montelukast treatment significantly increased MitoTracker red staining, suggesting that montelukast has an important impact in increasing mitochondrial mass. Induction of mtDNA expression mediated by TFAM is an essential event of mitochondrial biogenesis. Here, our findings indicate that the presence of montelukast significantly increased mtDNA/nDNA (Figure 3(B)). The mitochondrial protein cytochrome B is an important respiratory subunit. Consistently, montelukast remarkably upregulated the expression of cytochrome B (Figure 3(C)).