scholarly journals Carbonic Anhydrase Sensitivity to Pesticides: Perspectives for Biomarker Development

2020 ◽  
Vol 21 (10) ◽  
pp. 3562
Author(s):  
Maria Giulia Lionetto ◽  
Roberto Caricato ◽  
Maria Elena Giordano
Keyword(s):  
Carbonic Anhydrase ◽  
Environmental Medicine ◽  
Environmental Monitoring ◽  
Pesticide Exposure ◽  
Human Biomonitoring ◽  
Target Species ◽  
Physiological Processes ◽  
Occupational And Environmental Medicine

Carbonic anhydrase (CA) is a widespread metalloenzyme playing a pivotal role in several physiological processes. Many studies have demonstrated the in vitro and in vivo sensitivity of CA to the exposure to several classes of pesticides in both humans and wildlife. This review aims to analyze and to discuss the literature available in this field, providing a comprehensive view useful to foresee perspectives for the development of novel CA-based pesticide biomarkers. The analysis of the available data highlighted the ability of several pesticide molecules to interact directly with the enzyme in humans and wildlife and to inhibit CA activity in vitro and in vivo, with possible alterations of key physiological functions. The analysis disclosed key areas of further research and, at the same time, identified some perspectives for the development of novel CA-based sensitive biomarkers to pesticide exposure, suitable to be used in several fields from human biomonitoring in occupational and environmental medicine to environmental monitoring on non-target species.

scholarly journals A QUÍMICA NA AVALIAÇÃO DO IMPACTO À SAÚDE HUMANA DIANTE DA EXPOSIÇÃO AOS PESTICIDAS

Química Nova ◽  
2021 ◽  
Author(s):  
Jéssyca Medeiros ◽  
Raphael Acayaba ◽  
Cassiana Montagner
Keyword(s):  
Human Health ◽  
Pesticide Exposure ◽  
Human Health Risk ◽  
Human Biomonitoring ◽  
Epidemiological Studies ◽  
Target Species ◽  
Rural Environments ◽  
Pesticides Exposure

THE CHEMISTRY IN THE HUMAN HEALTH RISK ASSESSMENT DUE PESTICIDES EXPOSURE. Pesticides are widely used worldwide in urban and rural environments. Since most pesticides are not selective for target species the concern about possible impacts on human health has increased for the workers exposed to these substances (occupational exposure) and for the general population (environmental exposure). Epidemiological studies, in vivo and in vitro have associated several diseases with pesticide exposure, such as cancer, diabetes, Parkinson’s, and others. Therefore, chemistry plays an important role in evaluation of external (food and drinking water) and internal (human biomonitoring) exposure to pesticides through of analytical methodologies, for instance, chromatography coupled with mass spectrometry, proving to be an important complement in the evaluation of risks of pesticides in human health.

scholarly journals Protective effects of carbonic anhydrase inhibition in brain ischaemia in vitro and in vivo models

2021 ◽  
Vol 36 (1) ◽  
pp. 964-976
Author(s):  
Ilaria Dettori ◽  
Irene Fusco ◽  
Irene Bulli ◽  
Lisa Gaviano ◽  
Elisabetta Coppi ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Protective Effects ◽  
Brain Ischaemia ◽  
In Vivo Models ◽  
Carbonic Anhydrase Inhibition

scholarly journals DPP3/CDK1 contributes to the progression of colorectal cancer through regulating cell proliferation, cell apoptosis, and cell migration

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Yixin Tong ◽  
Yuan Huang ◽  
Yuchao Zhang ◽  
Xiangtai Zeng ◽  
Mei Yan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cell Apoptosis ◽  
Downstream Target ◽  
Normal Tissues ◽  
Physiological Processes ◽  
Mutual Regulation

AbstractAt present, colorectal cancer (CRC) has become a serious threat to human health in the world. Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase that may be involved in several physiological processes. However, whether DPP3 affects the development and progression of CRC remains a mystery. This study is the first to demonstrate the role of DPP3 in CRC. Firstly, the results of immunohistochemistry analysis showed the upregulation of DPP3 in CRC tissues compared with normal tissues, which is statistically analyzed to be positively correlated with lymphatic metastasis, pathological stage, positive number of lymph nodes. Moreover, the high expression of DPP3 predicts poor prognosis in CRC patients. In addition, the results of cell dysfunction experiments clarified that the downregulation of DPP3 significantly inhibited cell proliferation, colony formation, cell migration, and promoted apoptosis in vitro. DPP3 depletion could induce cell apoptosis by upregulating the expression of BID, BIM, Caspase3, Caspase8, HSP60, p21, p27, p53, and SMAC. In addition, downregulation of DPP3 can reduce tumorigenicity of CRC cells in vivo. Furthermore, CDK1 is determined to be a downstream target of DPP3-mediated regulation of CRC by RNA-seq, qPCR, and WB. The interaction between DPP3 and CDK1 shows mutual regulation. Specifically, downregulation of DPP3 can accentuate the effects of CDK1 knockdown on the function of CRC cells. Overexpression of CDK1 alleviates the inhibitory effects of DPP3 knockdown in CRC cells. In summary, DPP3 has oncogene-like functions in the development and progression of CRC by targeting CDK1, which may be an effective molecular target for the prognosis and treatment of CRC.

scholarly journals Crystal structure of human carbonic anhydrase II at 1.95 Å resolution in complex with 667-coumate, a novel anti-cancer agent

2005 ◽  
Vol 385 (3) ◽  
pp. 715-720 ◽  
Author(s):  
Matthew D. LLOYD ◽  
Richard L. PEDERICK ◽  
Ramanathan NATESH ◽  
L. W. Lawrence WOO ◽  
Atul PUROHIT ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Phase 1 ◽  
Structural Basis ◽  
Pharmacokinetic Studies ◽  
Reversible Binding ◽  
X Ray Crystallography ◽  
Hydrophobic Binding ◽  
Cancer Agent

CA (carbonic anhydrase) catalyses the reversible hydration of carbon dioxide into bicarbonate, and at least 14 isoforms have been identified in vertebrates. The role of CA type II in maintaining the fluid and pH balance has made it an attractive drug target for the treatment of glaucoma and cancer. 667-Coumate is a potent inhibitor of the novel oncology target steroid sulphatase and is currently in Phase 1 clinical trials for hormone-dependent breast cancer. It also inhibits CA II in vitro. In the present study, CA II was crystallized with 667-coumate and the structure was determined by X-ray crystallography at 1.95 Å (1 Å=0.1 nm) resolution. The structure reported here is the first for an inhibitor based on a coumarin ring and shows ligation of the sulphamate group to the active-site zinc at 2.15 Å through a nitrogen anion. The first two rings of the coumarin moiety are bound within the hydrophobic binding site of CA II. Important residues contributing to binding include Val-121, Phe-131, Val-135, Leu-141, Leu-198 and Pro-202. The third seven-membered ring is more mobile and is located in the channel leading to the surface of the enzyme. Pharmacokinetic studies show enhanced stability of 667-coumate in vivo and this has been ascribed to binding of CA II in erythrocytes. This result provides a structural basis for the stabilization and long half-life of 667-coumate in blood compared with its rapid disappearance in plasma, and suggests that reversible binding of inhibitors to CA may be a general method of delivering this type of labile drug.

Food supplement “carrageenan” and its effect on the organism

2020 ◽  
Author(s):  
O.E. Luneva ◽  
Keyword(s):  
Gastrointestinal Tract ◽  
Food Additives ◽  
Food Supplement ◽  
The Body ◽  
Laboratory Rats ◽  
Experimental Part ◽  
In Vivo Experiments ◽  
Physiological Processes

Food additives are positioned as harmless, although, their components affectthe physiological processes associated with the permeability of the wall of the gastrointestinal tract (GIT) and intestinal microbiota. This article describes thecarrageenan supplement and its effects on the body in in vitro and in vivo experiments. The experimental part is devoted to analysis of the intestinalmicrobiota of laboratory rats with the consumption of the carrageenan dietary supplement in the amount of about 4,4 % of the standard feed.

scholarly journals In Vitro and in Vivo Imaging of Nitroxyl with Copper Fluorescent Probe in Living Cells and Zebrafish

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2551 ◽  
Author(s):  
Sathyadevi Palanisamy ◽  
Yu-Liang Wang ◽  
Yu-Jen Chen ◽  
Chiao-Yun Chen ◽  
Fu-Te Tsai ◽  
...  
Keyword(s):  
Critical Role ◽  
Model Organism ◽  
Living Cells ◽  
Biological Species ◽  
Zebrafish Model ◽  
Physiological Processes ◽  
Collective Data ◽  
Angeli's Salt

Nitroxyl (HNO) plays a critical role in many physiological processes which includes vasorelaxation in heart failure, neuroregulation, and myocardial contractility. Powerful imaging tools are required to obtain information for understanding the mechanisms involved in these in vivo processes. In order to develop a rapid and high sensitive probe for HNO detection in living cells and the zebrafish model organism, 2-((2-(benzothiazole-2yl)benzylidene) amino)benzoic acid (AbTCA) as a ligand, and its corresponding copper(II) complex Cu(II)-AbTCA were synthesized. The reaction results of Cu(II)-AbTCA with Angeli’s salt showed that Cu(II)-AbTCA could detect HNO quantitatively in a range of 40–360 µM with a detection limit of 9.05 µM. Furthermore, Cu(II)-AbTCA is more selective towards HNO over other biological species including thiols, reactive nitrogen, and reactive oxygen species. Importantly, Cu(II)-AbTCA was successfully applied to detect HNO in living cells and zebrafish. The collective data reveals that Cu(II)-AbTCA could be used as a potential probe for HNO detection in living systems.

scholarly journals Polymorphisms in Brucella Carbonic anhydrase II mediate CO2 dependence and fitness in vivo

2019 ◽  
Author(s):  
JM García-Lobo ◽  
Y Ortiz ◽  
C González-Riancho ◽  
A Seoane ◽  
B Arellano-Reynoso ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Primary Cultures ◽  
Low Frequency ◽  
Carbonic Anhydrase Ii ◽  
Carbonic Anhydrases ◽  
Significant Difference ◽  
Dependent Strain

AbstractSome Brucella isolates are known to require an increased concentration of CO2 for growth, especially in the case of primary cultures obtained directly from infected animals. Moreover, the different Brucella species and biovars show a characteristic pattern of CO2 requirement, and this trait has been included among the routine typing tests used for species and biovar differentiation. By comparing the differences in gene content among different CO2-dependent and CO2-independent Brucella strains we have confirmed that carbonic anhydrase II (CA II), is the enzyme responsible for this phenotype in all the Brucella strains tested. Brucella species contain two carbonic anhydrases of the β family, CA I and CA II; genetic polymorphisms exist for both of them in different isolates, but only those putatively affecting the activity of CA II correlate with the CO2 requirement of the corresponding isolate. Analysis of these polymorphisms does not allow the determination of CA I functionality, while the polymorphisms in CA II consist of small deletions that cause a frameshift that changes the C-terminus of the protein, probably affecting its dimerization status, essential for the activity.CO2-independent mutants arise easily in vitro, although with a low frequency ranging from 10−6 to 10−10 depending on the strain. These mutants carry compensatory mutations that produce a full length CA II. At the same time, no change was observed in the sequence coding for CA I. A competitive index assay designed to evaluate the fitness of a CO2-dependent strain compared to its corresponding CO2-independent strain revealed that while there is no significant difference when the bacteria are grown in culture plates, growth in vivo in a mouse model of infection provides a significant advantage to the CO2-dependent strain. This could explain why some Brucella isolates are CO2-dependent in primary isolation. The polymorphism described here also allows the in silico determination of the CO2 requirement status of any Brucella strain.

scholarly journals USE OF MICRONUCLEUS EXPERIMENTS FOR THE DETECTION OF HUMAN CANCER RISKS: A BRIEF OVERVIEW

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Armen Nersesyan ◽  
◽  
Miroslav Mišík ◽  
Andriy Cherkas ◽  
Viktoria Serhiyenko ◽  
...  
Keyword(s):  
Blood Cells ◽  
Environmental Control ◽  
Human Cancer ◽  
Occupational Exposures ◽  
Human Biomonitoring ◽  
Target Cells ◽  
Cancer Risks ◽  
Wide Range

Introduction. Micronuclei (MN) are small extranuclear DNA-containing structures that are formed as a consequence of structural and numerical chromosomal aberrations. The advantage of MN experiments compared to conventional chromosomal analyses in metaphase cells is that the scoring is by far less time consuming and laborious. MN experiments are currently widely used for the routine screening of chemicals in vitro and in vivo but also for environmental control and human biomonitoring Objectives. The purpose of this review was to collect data on the use of MN experiments for the detection of increased cancer risks as a consequence of environmental, lifestyle and occupational exposures and the detection/diagnosis of different forms of cancer. Methods. Analysis of the literature on methods for MN experiments with humans; as well as the use of this technique in different areas of research. Results. To date, a wide range of protocols for human biomonitoring studies has been developed for the measurement of MN formation in peripheral blood cells and in epithelial from different organs (buccal and nasal cavity, cervix and bladder). In addition to MN, other nuclear anomalies can be scored which reflect genetic instability as well as acute toxicity and the division of target cells. Conclusions. The evidence is accumulating that MN can be used as a diagnostic tool for the detection of increased cancer risks as well as for the early diagnosis of cervical and bladder cancer

An Original Aspirin-Containing Carbonic Anhydrase 9 Inhibitor Overcomes Hypoxia-induced Drug Resistance to Enhance The Efficacy of Myocardial Protection

2021 ◽  
Author(s):  
Wen Zhou ◽  
Bin Zhang ◽  
Keyu Fan ◽  
Xiaojian Yin ◽  
Jinfeng Liu ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Carbonic Anhydrase ◽  
Myocardial Ischemia ◽  
Ph Value ◽  
Acquired Resistance ◽  
Vital Role ◽  
Carbonic Anhydrase 9 ◽  
Myocardial Hypoxia

Abstract Purpose Hypoxic microenvironment plays a vital role in myocardial ischemia injury, generally leading to the resistance of chemotherapeutic drugs. This induces an intriguing study on mechanism exploration and prodrug design to overcome the hypoxia induced drug resistance.Methods In this study, we hypothesized that the overexpression of carbonic anhydrase 9 (CAIX) in myocardial cells is closely related to the drug resistance. Herein, bioinformatics analysis, gene knockdown and overexpression assay certificated the correlation between CAIX overexpression and hypoxia. An original aspirin-containing CAIX inhibitor AcAs has been developed.Results Based on the downregulation of CAIX level, both in vitro and in vivo, AcAs can overcome the acquired resistance, and more effectively attenuate myocardial ischemia and hypoxia injury than that of aspirin. CAIX inhibitor is believed to recover the extracellular pH value so as to ensure the stable effect of aspirin.Conclusion Results indicate great potential of CAIX inhibitor for further application in myocardial hypoxia injury therapy.

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