enzyme isoforms
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Plants ◽  
2022 ◽  
Vol 11 (2) ◽  
pp. 175
Author(s):  
Gergana Mihailova ◽  
Ivanina Vasileva ◽  
Liliana Gigova ◽  
Emiliya Gesheva ◽  
Lyudmila Simova-Stoilova ◽  
...  

In this study, the contribution of nonenzymatic (ascorbate, glutathione) and enzymatic antioxidants (superoxide dismutase, catalase, glutathione reductase, glutathione S-transferase) in the first hours of recovery of the resurrection plant Haberlea rhodopensis from drought- and freezing-induced desiccation was assessed. The initial stage of recovery after desiccation is critical for plants, but less investigated. To better understand the alterations in the activity of antioxidant enzymes, their isoenzyme patterns were determined. Our results showed that ascorbate content remained high during the first 9 h of rehydration of desiccated plants and declined when the leaves′ water content significantly increased. The glutathione content remained high at the first hour of rehydration and then strongly decreased. The changes in ascorbate and glutathione content during recovery from drought- and freezing-induced desiccation showed great similarity. At the beginning of rehydration (1–5 h), the activities of antioxidant enzymes were significantly increased or remained as in dry plants. During 7–24 h of rehydration, certain differences in the enzymatic responses between the two plant groups were registered. The maintenance of a high antioxidant activity and upregulation of individual enzyme isoforms indicated their essential role in protecting plants from oxidative damage during the onset of recovery.


2021 ◽  
Vol 22 ◽  
Author(s):  
Haneen A . Basheer ◽  
Lina Elsalem ◽  
Anwar Salem ◽  
Artysha Tailor ◽  
Keith Hunter ◽  
...  

Background: The increased glutamine metabolism is a characteristic feature of cancer cells. The interconversion between glutamine and glutamate is catalyzed by two glutaminase isoforms, GLS1 and GLS2, which appear to have different roles in different types of cancer. We investigated for the first time the protein expression of GLS1 and GLS2, and their correlation with advanced clinicopathological parameters in head and neck cancers. Method: Consecutive slides from a tissue microarray comprised of 80 samples ranging from normal to metastatic, were stained immunohistochemically for GLS1, GLS2, HIF-1α or CD147. Following analysis by two expert pathologists we carried out statistical analysis of the scores. Results: GLS1 and GLS2 are upregulated at protein level in head and neck tumours compared to normal tissues and this increased expression correlated positively (GLS1) and negatively (GLS2) with tumor grade, indicating a shift of expression between GLS enzyme isoforms based on tumor differentiation. Increased expression of GLS1 was associated with high CD147 expression; and elevated GLS2 expression was associated with both high CD147 and high HIF-1α expressions. The correlation of the GLS1 and GLS2 with HIF-1α or CD147 was strongly associated with more advanced clinicopathological parameters. Conclusion: The increased expression of GLS1 and GLS2 may be explored as a new treatment for head and neck cancers.


2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Elahe Karimi ◽  
Emran Heshmati ◽  
Khosrow Khalifeh

Abstract We compared the binding properties and dynamics of three experimentally reviewed isoforms of human dihydrofolate reductase (DHFR). The cytoplasmic variants including isoforms1 and 2 (iso1 and iso2) are produced by alternative splicing; while the mitochondrial form is located in the mitochondria. The iso1 as the canonical sequence contains 187 residues, and iso2 differs from the iso1, where it has 1–52 residues missing at the N-terminus of canonical sequence. Here, the structural models of the iso2 and mitochondrial forms were constructed by the MODELLER program using the crystal structure of the iso1 as the template. Bioinformatics analysis on ligand-bearing structures demonstrates that mitochondrial variant forms more stable complex with ligands compared with iso1 and 2, indicating their different binding properties. The root mean square fluctuation (RMSF) data suggest that C-terminus of iso1 contains two representative highly flexible fragments, while iso2 contains a highly flexible fragment at N-terminus end. Interestingly, both ends of mitochondrial variant have a degree of rigidity. Finally, the observation of differences in structural dynamics and binding properties predicts that the simultaneous existence of enzyme isoforms is a way to increase the speed of the enzyme maneuver in response to various environmental conditions. This prediction needs to be tested experimentally.


2021 ◽  
Vol 28 (1) ◽  
Author(s):  
Kunal Nepali ◽  
Jing-Ping Liou

AbstractEpigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively to ascertain conclusive benefits in diverse malignancies. Literature precedents indicates that substantial amount of efforts were directed towards the use of epigenetic tools in monotherapy as well as in combination regimens at the clinical level, however, the preclinical/preliminary explorations were inclined towards the identification of prudent approaches that can leverage the anticancer potential of small molecule epigenetic inhibitors as single agents only. This review article presents an update of FDA approved epigenetic drugs along with the epigenetic inhibitors undergoing clinical stage investigations in different cancer types. A detailed discussion of the pragmatic strategies that are expected to steer the progress of the epigenetic therapy through the implementation of emerging approaches such as PROTACS and CRISPR/Cas9 along with logical ways for scaffold fabrication to selectively approach the enzyme isoforms in pursuit of garnering amplified antitumor effects has been covered. In addition, the compilation also presents the rational strategies for the construction of multi-targeting scaffold assemblages employing previously identified pharmacophores as potential alternatives to the combination therapy.


Processes ◽  
2020 ◽  
Vol 8 (11) ◽  
pp. 1424
Author(s):  
María Magdalena Vilchis-Landeros ◽  
Deyamira Matuz-Mares ◽  
Héctor Vázquez-Meza

Hydrogen peroxide (H2O2) is an important oxidizing molecule that regulates the metabolisms of aerobic organisms. Redox signaling comprises physiological oxidative stress (eustress), while excessive oxidative stress causes damage to molecules. The main enzymatic generators of H2O2 are nicotinamide adenine dinucleotide phosphate oxidases or NADPH oxidases (NOXs) and mitochondrial respiratory chains, as well as various oxidases. The NOX family is constituted of seven enzyme isoforms that produce a superoxide anion (O2−), which can be converted to H2O2 by superoxide dismutase or spontaneously. H2O2 passes through the membranes by some aquaporins (AQPs), known as peroxyporins. It diffuses through cells and tissues to initiate cellular effects, such as proliferation, the recruitment of immune cells, and cell shape changes. Therefore, it has been proposed that H2O2 has the same importance as Ca2+ or adenosine triphosphate (ATP) to act as modulators in signaling and the metabolism. The present overview focuses on the metabolic processes of liver and adipose tissue, regulated by the H2O2 generated by NOXs.


2020 ◽  
Author(s):  
Sharon Huws ◽  
Timofey Skvortsov ◽  
Fernanda Godoys Santos ◽  
Stephen Courtney ◽  
Karen Siu Ting ◽  
...  

Abstract BackgroundButyrivibrio and Pseudobutyrivibrio dominate in anaerobic gastrointestinal microbiomes, particularly the rumen, where they play a key role in harvesting energy from the diet. Within these genera, 5 rumen species have been classified (B. fibrisolvens, B. hungatei, B. proteoclasticus, P. ruminis and P. xylanivorans); nonetheless, the phylogeny and evolution of these genera is still unclear. Given the recent increase in available genomes, a re-investigation of the phylogenetic systematics and evolution of Butyrivibrio and Pseudobutyrivibrio is timely.ResultsWe show, using both a 16S rDNA and 40 gene marker phylogenetic tree, that 6 species, namely 1. P. ruminis, 2. P. xylanivorans, 3. B. fibrisolvens, 4. Butyrivibrio sp., 5. B. hungatei, and 6. B. proteclasticus likely exist. Pangenome analysis at 100% core definition showed a high abundance of accessory genes (91.50 to 99.34%) compared with core genes (0.66 to 8.50%), illustrating possession of very open genomes. Across the 71 genomes, 870 COGs (clusters of orthologous genes) were shared by all taxa, suggesting evolution through speciation from a common ancestor. Further analysis of Carbohydrate-Active Enzymes (CAZymes) genes show that most are within the accessory genome and orthologous in descent with numerous within-family CAZyme isoforms apparent, CAZyme family tree lineages show that these isoforms largely group according to the 6 species, suggesting extensive horizontal gene transfer within these families.ConclusionsWe show the extensive genomic variation found within Butyrivibrio, and to a lesser extent, Pseudobutyrivibrio. and demonstrate the existence of a new Butyrivibrio species. The Butyrivibrio and Pseudobutyrivibrio genomes are very open with very low % core genomes and high % accessory genomes., and possess a number of GH isoforms that we hypothesise facilitate metabolic plasticity and resilience under dietary perturbations. This study utilizes all currently available genomes and consequently provides a major advancement in our understanding of these important anaerobic bacteria.


Botanica ◽  
2020 ◽  
Vol 26 (1) ◽  
pp. 28-39
Author(s):  
Ekaterina Stoynova-Bakalova ◽  
Natalia Ivanova ◽  
Dimitar Bakalov ◽  
Liliana Gigova

AbstractThe aim of the study was to investigate the potential beneficial effects of exogenous application of methyl jasmonate (MeJa) and phenylurea cytokinin (4PU-30) on zucchini (Cucurbita pepo L.) cotyledons subjected to high temperature (HT) and combined HT plus excess copper (Cu2+) stress. Compared to HT stressed zucchini cotyledons, exposure to excess Cu2+ prior to HT treatment inhibited the growth, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities, increased glutathione-Stransferase (GST) and peroxidase (Px) total activities, and induced new enzyme isoforms (GST4, GST8, and Px4). The effect of MeJa on the double-stressed plants was to increase SOD, GPx and Px total activities and stimulate the activity of GST8, GST9, GST10, SOD5, Px3 and Px8 isoenzymes. In addition to SOD, GPx and Px, 4PU-30 increased GST total activity, up-regulated Px1 and GR1, and had a higher stimulatory effect on SOD5, Px3, GPx3, GST9 and GST10 activities. Copper, 4PU-30 and MeJa treatments changed the abundance and pattern (MeJa) of soluble zucchini polypeptides in a specific manner. MeJa and especially 4PU-30 applied alone, or in combination, stimulated the growth of later HT-treated cotyledons. 4PU-30 counteracted better than MeJa in the HT+heavy metal-caused inhibition of the growth. The data indicated that both MeJa and 4PU- 30 may protect the zucchini plants from high temperature and combined high temperature plus excess copper stress, but 4PU-30 was more effective; the protective effect was related to the changes in the gene expression, total antioxidant enzyme activities and the activity of individual isoforms of the enzymes.


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