scholarly journals STUDY OF THE PHARMACOLOGICAL ACTIVITY OF NOVEL EPOR/CD131 HETERORECEPTOR AGONISTS IN MICE WITH ENDOTHELIAL-SPECIFIC EXPRESSION OF MUTANT POLG GENE

2021 ◽  
Vol 9 (4) ◽  
pp. 294-305
Author(s):  
М. В. Korokin ◽  
M. V. Kubekina ◽  
A. V. Deykin ◽  
O. V. Antsiferov ◽  
V. M. Pokrovskii ◽  
...  

The aim of the research was to study antiatherosclerotic and endothelial kinds of a protective activity of peptides mimicking an erythropoietin a-helix B tertiary structure with laboratory codes EP-11-1 (UEHLERALNSS), EP-11-2. (UEQLERALNCS), EP-11-3 (UEQLERALNTS).Materials and methods. The study was conducted on 96 C57Bl/6J male double transgenic Polgmut/mut/Cdh5-CRE mice. Atherosclerosis was induced by a balloon injury accompanied by Western diet. Then, for 27 days, the drugs under study were administered once per 3 days at the dose of 20 μg/kg. On the 28th day, the animals were euthanized and the area of atherosclerotic plaques was collected for an assessment. The expression of genes associated with the processes of inflammation, apoptosis, and angiogenesis was determined in the tissues of the aorta. In addition, the endothelial protective effect of peptides in isolated segments of the thoracic aorta of wild and transgenic ransgenic Polgmut/mut mice was studied.Results. The assessment of the plaque size in the animals with the Polgmut/mut/Cdh5-CRE genotype against the background of the peptides under study did not reveal statistically significant differences in comparison to control. However, a quantitative PCR showed a statistically significant decreased expression of pro-apoptotic factors p-53 and Bax, and also increase the expression of anti-apoptotic factor Bcl-2 against the background of the peptides EP-11-1 and EP-11-2 administration. The administration of EP-11-1 and the original peptide pHBSP resulted in a statistically significant decrease in the Bax/Bcl-2 ratio. Compounds EP-11-1, EP-11-2, and EP-11-3 were more effective than the original peptide pHBSP, in reducing the increased expression of genes for inflammatory markers iNos, intercellular adhesion molecules Icam-1, Vcam-1 and E-selectin. The use of EP-11-1 led to a more efficient, in comparison with pHBSP, restoration of endothelial-dependent vasodilation of the aortic segments in mice with endothelial-specific overexpression of the mutant Polg gene.Conclusion. The study carried out on a murine model of the endothelial-specific expression of mutant gamma polymerase has shown that derivatives of the pHBSP peptide with laboratory codes EP-11-1, EP-11-2, EP-11-3, obtained by BLAST-searching for groups of pHBSP related peptides, have atheroprotective and endothelial protective kinds of a protective activity, which is more pronounced in comparison with the original peptide pHBSP.

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Longmei Zhai ◽  
Xiaomin Wang ◽  
Dan Tang ◽  
Qi Qi ◽  
Huseyin Yer ◽  
...  

AbstractsGrafting is a highly useful technique, and its success largely depends on graft union formation. In this study, we found that root-specific expression of the auxin biosynthetic gene iaaM in tobacco, when used as rootstock, resulted in more rapid callus formation and faster graft healing. However, overexpression of the auxin-inactivating iaaL gene in rootstocks delayed graft healing. We observed increased endogenous auxin levels and auxin-responsive DR5::GUS expression in scions of WT/iaaM grafts compared with those found in WT/WT grafts, which suggested that auxin is transported upward from rootstock to scion tissues. A transcriptome analysis showed that auxin enhanced graft union formation through increases in the expression of genes involved in graft healing in both rootstock and scion tissues. We also observed that the ethylene biosynthetic gene ACS1 and the ethylene-responsive gene ERF5 were upregulated in both scions and rootstocks of the WT/iaaM grafts. Furthermore, exogenous applications of the ethylene precursor ACC to the junction of WT/WT grafts promoted graft union formation, whereas application of the ethylene biosynthesis inhibitor AVG delayed graft healing in WT/WT grafts, and the observed delay was less pronounced in the WT/iaaM grafts. These results demonstrated that elevated auxin levels in the iaaM rootstock in combination with the increased auxin levels in scions caused by upward transport/diffusion enhanced graft union formation and that ethylene was partially responsible for the effects of auxin on grafting. Our findings showed that grafting success can be enhanced by increasing the auxin levels in rootstocks using transgenic or gene-editing techniques.


BMC Genomics ◽  
2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Chenxu Ye ◽  
Humaira Rasheed ◽  
Yuehua Ran ◽  
Xiaojuan Yang ◽  
Lianxi Xing ◽  
...  

Abstract Background The reproductive plasticity of termite workers provides colonies with tremendous flexibility to respond to environmental changes, which is the basis for evolutionary and ecological success. Although it is known that all colony members share the same genetic background and that differences in castes are caused by differences in gene expression, the pattern of the specific expression of genes involved in the differentiation of workers into reproductives remains unclear. In this study, the isolated workers of Reticulitermes labralis developed into reproductives, and then comparative transcriptomes were used for the first time to reveal the molecular mechanisms underlying the reproductive plasticity of workers. Results We identified 38,070 differentially expressed genes and found a pattern of gene expression involved in the differentiation of the workers into reproductives. 12, 543 genes were specifically upregulated in the isolated workers. Twenty-five signal transduction pathways classified into environmental information processing were related to the differentiation of workers into reproductives. Ras functions as a signalling switch regulates the reproductive plasticity of workers. The catalase gene which is related to longevity was up-regulated in reproductives. Conclusion We demonstrate that workers leaving the natal colony can induce the expression of stage-specific genes in the workers, which leads to the differentiation of workers into reproductives and suggests that the signal transduction along the Ras-MAPK pathway crucially controls the reproductive plasticity of the workers. This study also provides an important model for revealing the molecular mechanism of longevity changes.


2019 ◽  
Author(s):  
Wenbo Liu ◽  
Jun Ni ◽  
Faheem Shah ◽  
Kaiqin Ye ◽  
Hao Hu ◽  
...  

APYRASEs, which directly regulated the intra- and extra-cellular ATP homeostasis, plays a pivotal role in the regulation of the adaptations to various stresses in mammals, bacteria and plants. In the present study, we identified and characterized the wheat APYRASE family members at the genomic level. The results showed that a total of eight APY homologs with conserved ACR domains were identified. The wheat APYs were further analyzed bioinformatically of their sequence alignment, phylogenetic relations and conserved motifs. Although they share highly conserved secondary structure and tertiary structure, the wheat APYs could be mainly categorized into three groups, according to the phylogenetic and structural analysis. Further, these APYs exhibited similar expression patterns in the root and shoot, among which TaAPY3-1 and TaAPY3-3 had the highest expression level. The time-course expression patterns of the eight APYs in the wheat seedlings in response to the biotic stress and abiotic stress were also investigated. TaAPY3-2, TaAPY3-3, and TaAPY6 exhibited strong sensitivity to all kinds of stresses in the leaves. Some APYs showed specific expression responses, such as TaAPY6 to the heavy metal stress, and TaAPY7 to the heat and salt stress. These results suggested that the stress-inducible APYs could have potential roles in the regulation of the adaptation to the environmental stresses. Moreover, the catalytic activity of TaAPY3-1 was further analyzed in the in vitro system. The results showed that TaAPY3-1 protein exhibited high catalytic activity in degradation of ATP and ADP, but not GTP, CTP and TTP. It also has an extensive range of temperature adaptability, but rather preferred relative acid pH conditions. In this study, the genome-wide identification and characterization of the APYs in wheat could be useful for further genetic modifications to generate high-stress tolerant wheat cultivars.


1992 ◽  
Vol 6 (3) ◽  
pp. 626-634 ◽  
Author(s):  
Ganesh M. Kishore ◽  
Stephen R. Padgette ◽  
Robert T. Fraley

Weed management is an integral part of agriculture; weeds lower both productivity and quality of agricultural products. A combination of mechanical, chemical, biological, and cultural methods is expected to deliver a sustainable weed management program for the next two decades. While chemical methods offer the most cost effective means of weed management, crop selectivity has hampered the use of the best chemicals for weed management. Recent progress in gene technology has facilitated the introduction and expression of genes to confer a wide range of traits to crop plants. Application of this technology has resulted in the development of crop plant genotypes that are resistant to a specific herbicide. This article describes the progress that has been made by our group toward the introduction of glyphosate tolerance to crop plants. Glyphosate [N-(phosphonomethyl)glycine] kills plants due to inhibition of the biosynthesis of aromatic compounds via the shikimate pathway. Our approach for introduction of glyphosate tolerance is based on insertion and expression in plants of a gene encoding a glyphosate-tolerant 5-enolpyruvylshikimate-3-phosphate (EPSP) synthase, a key enzyme of the shikimate pathway. The wild type enzyme present in plants is susceptible to inhibition glyphosate; variants of EPSP synthase have been produced that are less susceptible to inhibition by glyphosate. Expression of genes encoding these variants has been shown to confer glyphosate tolerance to plants. The degree of glyphosate tolerance is related to the tolerance characteristics of the EPSP synthase variant, its substrate activity, targeting to the plastid, and the level of expression of the variant gene. The tissue specificity of expression of the variant EPSP synthase has also been shown to be critical since glyphosate is a systemic herbicide and is translocated to many growing points within the plant. Our studies on glyphosate tolerance have substantially enhanced our understanding of the mode-of-action of glyphosate, the shikimate pathway, and protein sorting within plant cells, as well as developmental and tissue specific expression of genes in plants. Commercial use of glyphosate tolerance technology is expected to affect positively, the weed management arsenal available to the farmers, the sustainability of farm land and groundwater, and promote the use of a “soft” herbicide.


Insects ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 186
Author(s):  
Ruizheng Tian ◽  
Yixiao Huang ◽  
Balachandar Balakrishnan ◽  
Maohua Chen

The pea aphid is a global insect pest, and variable phenotypes can be produced by pea aphids in the same genotype in response to changes in external environmental factors. However, detailed dynamic gene regulation networks and the core markers involved in different biological processes of pea aphids have not yet been reported. In this study, we obtained the published genomic and transcriptomic data, and performed transcriptome profiling of five pea aphid morphs (winged asexual female, wingless asexual female, wingless sexual female, winged male and wingless male) from each of three pea aphid genotypes, i.e., the transcriptomes from a total of 15 types of pea aphids were analyzed and the type-specific expression of genes in five different morphs was identified. The expression profiling was verified by quantitative real-time PCR (qPCR) analysis. Moreover, we determined the expression features and co-expression networks of highly variable genes. We also used the ARACNe method to obtain 263 core genes related to different biological pathways. Additionally, eight of the identified genes were aligned with transcription factor families, indicating that they act as transcription factors and regulate downstream genes. Furthermore, we found reliable markers using random forest methodology to distinguish different morphs of pea aphids. Our study provides a systematic and comprehensive approach for analyzing the core genes that may play important roles in a multitude of biological processes from the insect transcriptomes.


1969 ◽  
Vol 47 (2) ◽  
pp. 143-151 ◽  
Author(s):  
I. G. Walker ◽  
J. F. Smith

The lethal effect of sulfur mustard on L-cells was reduced by pretreating the cells with dithiothreitol (DTT), aminoethylisothiuronium bromide, mercaptoethylamine, and some alkyl derivatives of this compound. The disulfides of these agents were without protective activity. The protective mechanism by which DTT operated involved a simple inactivation of the sulfur mustard. This deduction was based on the finding that alkylation by mustard of cellular DNA, RNA, and protein was reduced by DTT treatment in parallel with the reduction in toxicity of the mustard. DTT at a tolerated dose of 100 mg/kg provided scant protection to mice against the nitrogen mustard HN2.


2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Sophie Tandonnet ◽  
Gisele Antoniazzi Cardoso ◽  
Pedro Mariano-Martins ◽  
Raquel Dietsche Monfardini ◽  
Vanessa A. S. Cunha ◽  
...  

Abstract Background The emergence of insecticide resistance is a fast-paced example of the evolutionary process of natural selection. In this study, we investigated the molecular basis of resistance in the myiasis-causing fly Cochliomyia hominivorax (Diptera: Calliphoridae) to dimethyl-organophosphate (OP) insecticides. Methods By sequencing the RNA from surviving larvae treated with dimethyl-OP (resistant condition) and non-treated larvae (control condition), we identified genes displaying condition-specific polymorphisms, as well as those differentially expressed. Results Both analyses revealed that resistant individuals have altered expression and allele-specific expression of genes involved in proteolysis (specifically serine-endopeptidase), olfactory perception and cuticle metabolism, among others. We also confirmed that resistant individuals carry almost invariably the Trp251Ser mutation in the esterase E3, known to confer OP and Pyrethroid resistance. Interestingly, genes involved in metabolic and detoxifying processes (notably cytochrome P450s) were found under-expressed in resistant individuals. An exception to this were esterases, which were found up-regulated. Conclusions These observations suggest that reduced penetration and aversion to dimethyl-OP contaminated food may be important complementary strategies of resistant individuals. The specific genes and processes found are an important starting point for future functional studies. Their role in insecticide resistance merits consideration to better the current pest management strategies.


2005 ◽  
Vol 94 (3) ◽  
pp. 763-773 ◽  
Author(s):  
Sunita Gopalan ◽  
Aneta Kasza ◽  
Weili Xu ◽  
Daniel L. Kiss ◽  
Katarzyna M. Wilczynska ◽  
...  

Blood ◽  
1999 ◽  
Vol 94 (6) ◽  
pp. 1855-1863 ◽  
Author(s):  
Sarah Ogilvy ◽  
Donald Metcalf ◽  
Leonie Gibson ◽  
Mary L. Bath ◽  
Alan W. Harris ◽  
...  

To develop a method for targeting expression of genes to the full hematopoietic system, we have used transgenic mice to explore the transcriptional regulation of the vav gene, which is expressed throughout this compartment but rarely outside it. Previously, we showed that a cluster of elements surrounding its promoter could drive hematopoietic-specific expression of a bacterial lacZ reporter gene, but the expression was confined to lymphocytes and was sporadically silenced. Those limitations are ascribed here to the prokaryotic reporter gene. With a human CD4 (hCD4) cell surface reporter, the vav promoter elements drove expression efficiently and stably in virtually all nucleated cells of adult hematopoietic tissues but not notably in nonhematopoietic cell types. In multiple lines, hCD4 appeared on most, if not all, B and T lymphocytes, granulocytes, monocytes, megakaryocytes, eosinophils, and nucleated erythroid cells. Moreover, high levels appeared on both lineage-committed progenitors and the more primitive preprogenitors. In the fetus, expression was evident in erythroid cells of the definitive but not the primitive type. These results indicate that a prokaryotic sequence can inactivate a transcription unit and that the vavpromoter region constitutes a potent transgenic vector for the entire definitive hematopoietic compartment.


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