scholarly journals Glucosidase Inhibitors Screening in Microalgae and Cyanobacteria Isolated from the Amazon and Proteomic Analysis of Inhibitor Producing Synechococcus sp. GFB01

2021 ◽  
Vol 9 (8) ◽  
pp. 1593
Author(s):  
Diana Gomes Gradíssimo ◽  
Vivian Cássia Oliveira da Silva ◽  
Luciana Pereira Xavier ◽  
Sidney Vasconcelos do Nascimento ◽  
Rafael Borges da Silva Valadares ◽  
...  

Microalgae and cyanobacteria are good sources for prospecting metabolites of biotechnological interest, including glucosidase inhibitors. These inhibitors act on enzymes related to various biochemical processes; they are involved in metabolic diseases, such as diabetes and Gaucher disease, tumors and viral infections, thus, they are interesting hubs for the development of new drugs and therapies. In this work, the screening of 63 environmental samples collected in the Brazilian Amazon found activity against β-glucosidase, of at least 60 min, in 13.85% of the tested extracts, with Synechococcus sp. GFB01 showing inhibitory activity of 90.2% for α-glucosidase and 96.9% against β-glucosidase. It was found that the nutritional limitation due to a reduction in the concentration of sodium nitrate, despite not being sufficient to cause changes in cell growth and photosynthetic apparatus, resulted in reduced production of α and β-glucosidase inhibitors and differential protein expression. The proteomic analysis of cyanobacteria isolated from the Amazon is unprecedented, with this being the first work to evaluate the protein expression of Synechococcus sp. GFB01 subjected to nutritional stress. This evaluation helps to better understand the metabolic responses of this organism, especially related to the production of inhibitors, adding knowledge to the industrial potential of these cyanobacterial compounds.

2018 ◽  
Vol 25 (23) ◽  
pp. 2637-2660 ◽  
Author(s):  
Francesco Miceli ◽  
Maria V. Soldovieri ◽  
Paolo Ambrosino ◽  
Laura Manocchio ◽  
Ilaria Mosca ◽  
...  

Background: The Kv7 (KCNQ) subfamily of voltage-gated potassium channels consists of 5 members (Kv7.1-5) each showing characteristic tissue distribution and physiological roles. Given their functional heterogeneity, Kv7 channels represent important pharmacological targets for the development of new drugs for neuronal, cardiovascular and metabolic diseases. <p> Objective: In the present manuscript, we focus on describing the pharmacological relevance and potential therapeutic applications of drugs acting on neuronally-expressed Kv7.2/3 channels, placing particular emphasis on the different chemotypes, and highlighting their pharmacodynamic and, whenever possible, pharmacokinetic peculiarities. <p> Methods: The present work is based on an in-depth search of the currently available scientific literature, and on our own experience and knowledge in the field of neuronal Kv7 channel pharmacology. Space limitations impeded to describe the full pharmacological potential of Kv7 channels; thus, we have chosen to focus on neuronal channels composed of Kv7.2 and Kv7.3 subunits, and to mainly concentrate on their involvement in epilepsy. <p> Results: An astonishing heterogeneity in the molecular scaffolds exploitable to develop Kv7.2/3 modulators is evident, with important structural/functional peculiarities of distinct compound classes. <p> Conclusion: In the present work we have attempted to show the current status and growing potential of the Kv7 pharmacology field. We anticipate a bright future for the field, and express our hopes that the efforts herein reviewed will result in an improved treatment of hyperexcitability (or any other) diseases.


2019 ◽  
Vol 26 (31) ◽  
pp. 5849-5861 ◽  
Author(s):  
Pan Jiang ◽  
Feng Yan

tiRNAs & tRFs are a class of small molecular noncoding tRNA derived from precise processing of mature or precursor tRNAs. Most tiRNAs & tRFs described originate from nucleus-encoded tRNAs, and only a few tiRNAs and tRFs have been reported. They have been suggested to play important roles in inhibiting protein synthesis, regulating gene expression, priming viral reverse transcriptases, and the modulation of DNA damage responses. However, the regulatory mechanisms and potential function of tiRNAs & tRFs remain poorly understood. This review aims to describe tiRNAs & tRFs, including their structure, biological functions and subcellular localization. The regulatory roles of tiRNAs & tRFs in translation, neurodegeneration, metabolic diseases, viral infections, and carcinogenesis are also discussed in detail. Finally, the potential applications of these noncoding tRNAs as biomarkers and gene regulators in different diseases is also highlighted.


2020 ◽  
Vol 17 ◽  
Author(s):  
Qian Lu ◽  
Hai-Zhu Xing ◽  
Nian-Yun Yang

Background: CCl4 acute liver injury (ALI) is a classical model for experimental research. However, there are few reports involved in the fundamental research of CCl4-induced ALI Ligustri Lucidi Fructus (LLF) are and its prescription have been used to treat hepatitis illness clinically. LLF and its active ingredients displayed anti-hepatitis effects, but the mechanism of function has not been fully clarified Objective: To investigate the proteomic analysis of CCl4-induced ALI, and examine the effects of active total glycosides (TG) from LLF on ALI of mice4, including histopathological survey and proteomic changes of liver tissues, and delineate the possible underlying mechanism. Methods: CCl4 was used to produce ALI mice model. The model mice were intragastrically administrated with TG and the liver his-topathological changes of mice were examined. At the end of test, mice liver samples were collected, after protein denaturation, re-duction, desalination and enzymatic hydrolysis, identification was carried out by nano LC-ESI-OrbiTrap MS/MS technology. The data was processed by Maxquant software. The differentially-expressed proteins were screened and identified, and their biological information was also analyzed based on GO and KEGG analysis. Key protein expression was validated by Western blot analysis Results: A total of 705 differentially-expressed proteins were identified during the normal, model and administration group. 9 signifi-cant differential proteins were focused based on analysis. Liver protein expression changes of CCl4-induced ALI mice were mainly involved in several important signal channels, namely FoxO signaling pathway, autophagy-animal, insulin signaling pathway. TG has anti-liver damnification effect in ALI mice, the mechanism of which is related to FoxO1 and autophagy pathways Conclusion: CCl4 inhibited expression of insulin-Like growth factor 1 (Igf1) and 3-phosphoinositide-dependent protein kinase 1 (Pdpk1) in liver cells and induced insulin resistance, thus interfered with mitochondrial autophagy and regeneration of liver cells and the metabolism of glucose and lipid, and caused hepatic necrosis in mice. TG resisted liver injury in mice. TG adjusted the expression level of key proteins Igf1 and Pdpk1 after liver injury and improved insulin resistance, thus promoted autophagy and resisted the liver damage


PPAR Research ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-16 ◽  
Author(s):  
Marion Peyrou ◽  
Pierluigi Ramadori ◽  
Lucie Bourgoin ◽  
Michelangelo Foti

Peroxisome-proliferator-activated receptors (PPARs) are ligand-activated nuclear receptors that exert in the liver a transcriptional activity regulating a whole spectrum of physiological functions, including cholesterol and bile acid homeostasis, lipid/glucose metabolism, inflammatory responses, regenerative mechanisms, and cell differentiation/proliferation. Dysregulations of the expression, or activity, of specific PPAR isoforms in the liver are therefore believed to represent critical mechanisms contributing to the development of hepatic metabolic diseases, disorders induced by hepatic viral infections, and hepatocellular adenoma and carcinoma. In this regard, specific PPAR agonists have proven to be useful to treat these metabolic diseases, but for cancer therapies, the use of PPAR agonists is still debated. Interestingly, in addition to previously described mechanisms regulating PPARs expression and activity, microRNAs are emerging as new important regulators of PPAR expression and activity in pathophysiological conditions and therefore may represent future therapeutic targets to treat hepatic metabolic disorders and cancers. Here, we reviewed the current knowledge about the general roles of the different PPAR isoforms in common chronic metabolic and infectious liver diseases, as well as in the development of hepatic cancers. Recent works highlighting the regulation of PPARs by microRNAs in both physiological and pathological situations with a focus on the liver are also discussed.


2018 ◽  
Vol 47 (6) ◽  
pp. 1259-1268 ◽  
Author(s):  
Marhaini Mostapha ◽  
Noorhasmiera Abu Jahar ◽  
Kamalrul Azlan Azizan ◽  
Sarani Zakaria ◽  
Wan Mohd Aizat ◽  
...  

2021 ◽  
Vol 97 (6) ◽  
pp. 578-586
Author(s):  
N. A. Plekhanov ◽  
S. P. Zadnova ◽  
A. A. Kritsky ◽  
T. A. Polunina ◽  
N. V. Kotova ◽  
...  

Objective — comparative study of protein expression in typical and genetically altered Vibrio cholerae strains of O1 serogroup, biovar El Tor by means of proteomic analysis.Materials and methods. Clinical V. cholerae strains — typical strain, M106 (Astrakhan, 1970) and genetically altered one, M1509 (Moscow, 2012) — were used as model ones. Strains were cultivated in LB broth (pH7.2). Then, cell and exoprotein lysate fractions were obtained and investigated in 2D electrophoresis. Different protein stains were examined using mass spectrometry. Survivability of V. cholerae strains under osmotic and oxidative stresses was studied during incubation of the strains in 3 M NaCl solution or 20 mM H2O2 solution.Results and discussion. When analyzing cell lysates, significant differences in protein expression with known function between studied strains were not detected. The great majority of identified proteins in the lysates is functionally associated with carbohydrate metabolism, amino acid metabolism, and energy processes in a cell. At the same time, exoprotein fraction of M1509 genovariant contained increased amount of proteins (peroxidase, superoxide dismutase, thioredoxin, outer membrane proteins OmpW, OmpT) protecting the cells of cholera vibrio from effect of stress factors of the environment. Further study of the resistance to osmotic and oxidative stresses revealed better survivability in the genovariant when exposed to the stated factors.Conclusion. The data of proteomic analysis of the typical and genetically altered V. cholera strains, biovar El Tor, testify to high levels of expression of the proteins that provide for vibrio resistance to the effect of environmental stress factors in genovariants, which is possibly one of the causes of their wide dissemination. In addition, the results obtained will allow for identification of new biomarkers which can be used for differentiation of typical strains and genovariants of V. cholerae, biovar El Tor.


Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2449
Author(s):  
Zhipeng Gao ◽  
Weiming Zhong ◽  
Ting Liu ◽  
Tianyu Zhao ◽  
Jiajing Guo

Listeria monocytogenes (LM) is one of the most serious foodborne pathogens. Listeriosis, the disease caused by LM infection, has drawn attention worldwide because of its high hospitalization and mortality rates. Linalool is a vital constituent found in many essential oils; our previous studies have proved that linalool exhibits strong anti-Listeria activity. In this study, iTRAQ-based quantitative proteomics analysis was performed to explore the response of LM exposed to linalool, and to unravel the mode of action and drug targets of linalool against LM. A total of 445 differentially expressed proteins (DEPs) were screened out, including 211 up-regulated and 234 down-regulated proteins which participated in different biological functions and pathways. Thirty-one significantly enriched gene ontology (GO) functional categories were obtained, including 12 categories in “Biological Process”, 10 categories in “Cell Component”, and 9 categories in “Molecular Function”. Sixty significantly enriched biological pathways were classified, including 6 pathways in “Cell Process”, 6 pathways in “Environmental Information Processing”, 3 pathways in “Human Disease”, 40 pathways in “Metabolism”, and 2 pathways in “Organic System”. GO and Kyoto Encyclopedia of Genes (KEGG) enrichment analysis together with flow cytometry data implied that cell membranes, cell walls, nucleoids, and ribosomes might be the targets of linalool against LM. Our study provides good evidence for the proteomic analysis of bacteria, especially LM, exposed to antibacterial agents. Further, those drug targets discovered by proteomic analysis can provide theoretical support for the development of new drugs against LM.


2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Xiaobei Ni ◽  
Xin Li ◽  
Yueshuai Guo ◽  
Tao Zhou ◽  
Xuejiang Guo ◽  
...  

Many pregnant women suffer miscarriages during early gestation, but the description of these early pregnancy losses (EPL) can be somewhat confusing because of the complexities of early development. Thus, the identification of proteins with different expression profiles related to early pregnancy loss is essential for understanding the comprehensive pathophysiological mechanism. In this study, we report a gel-free tandem mass tags- (TMT-) labeling based proteomic analysis of five placental villous tissues from patients with early pregnancy loss and five from normal pregnant women. The application of this method resulted in the identification of 3423 proteins and 19647 peptides among the patient group and the matched normal control group. Qualitative and quantitative proteomic analysis revealed 51 proteins to be differentially abundant between the two groups (≥1.2-fold, Student'st-test,P<0.05). To obtain an overview of the biological functions of the proteins whose expression levels altered significantly in EPL group, gene ontology analysis was performed. We also investigated the twelve proteins with a difference over 1.5-fold using pathways analysis. Our results demonstrate that the gel-free TMT-based proteomic approach allows the quantification of differences in protein expression levels, which is useful for obtaining molecular insights into early pregnancy loss.


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