Paradoxical role of C1561T glutamate carboxypeptidase II (GCPII) genetic polymorphism in altering disease susceptibility

Gene ◽  
2012 ◽  
Vol 497 (2) ◽  
pp. 273-279 ◽  
Author(s):  
Shree Divyya ◽  
Shaik Mohammad Naushad ◽  
Anthony Addlagatta ◽  
P.V.L.N. Murthy ◽  
Ch Ram Reddy ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Disease Susceptibility ◽  
Glutamate Carboxypeptidase Ii ◽  
Glutamate Carboxypeptidase

scholarly journals Determination of the Role of Glutamate Carboxypeptidase II Paralogs in Folate Metabolism in Caenorhabditis elegans

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Jessica M. Derham ◽  
Hashni E. Gamage ◽  
Claire M. Kennedy ◽  
Gopal R. Periyannan
Keyword(s):  
Caenorhabditis Elegans ◽  
Folate Metabolism ◽  
Glutamate Carboxypeptidase Ii ◽  
Glutamate Carboxypeptidase

Association of genetic polymorphism of cytokines and antioxidant enzymes with the development of asbestosis

2020 ◽  
Vol 60 (12) ◽  
pp. 898-903
Author(s):  
Lyudmila P. Kuzmina ◽  
Anastasiya G. Khotuleva ◽  
Evgeniy V. Kovalevsky ◽  
Nikolay N. Anokhin ◽  
Iraklij M. Tskhomariya
Keyword(s):  
Antioxidant Enzymes ◽  
Genetic Polymorphism ◽  
Genetic Predisposition ◽  
Risk Groups ◽  
Dust Exposure ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Gstp1 Gene ◽  
Polymorphic Variants

Introduction. Various industries widely use chrysotile asbestos, which determines the relevance of research aimed at the prevention of asbestos-related diseases. It is promising to assess the role of specific genes, which products are potentially involved in the development and regulation of certain links in the pathogenesis of asbestosis, forming a genetic predisposition to the disease. The study aims to analyze the presence of associations of genetic polymorphism of cytokines and antioxidant enzymes with asbestosis development. Materials and methods. Groups were formed for examination among employees of OJSC "Uralasbest" with an established diagnosis of asbestosis and without lung diseases. For each person included in the study, dust exposure doses were calculated considering the percentage of time spent at the workplace during the shift for the entire work time. Genotyping of single nucleotide polymorphisms of cytokines IL1b (rs16944), IL4 (rs2243250), IL6 (rs1800795), TNFα (rs1800629) and antioxidant enzymes SOD2 (rs4880), GSTP1 (rs1610011), CAT (rs1001179) was carried out. Results. The authors revealed the associations of polymorphic variants A511G IL1b gene (OR=2.457, 95% CI=1.232-4.899) and C47T SOD2 gene (OR=1.705, 95% CI=1.055-2.756) with the development of asbestosis. There was an increase in the T allele IL4 gene (C589T) frequency in persons with asbestosis at lower values of dust exposure doses (OR=2.185, 95% CI=1.057-4.514). The study showed the associations of polymorphism C589T IL4 gene and C174G IL6 gene with more severe asbestosis, polymorphism A313G GSTP1 gene with pleural lesions in asbestosis. Conclusion. Polymorphic variants of the genes of cytokines and antioxidant enzymes, the protein products directly involved in the pathogenetic mechanisms of the formation of asbestosis, contribute to forming a genetic predisposition to the development and severe course of asbestosis. Using the identified genetic markers to identify risk groups for the development and intense period of asbestos-related pathology will optimize treatment and preventive measures, considering the organism's characteristics.

Design, Synthesis, and Pharmacological Evaluation of Glutamate Carboxypeptidase II (GCPII) Inhibitors Based on Thioalkylbenzoic Acid Scaffolds

2012 ◽  
Vol 55 (12) ◽  
pp. 5922-5932 ◽  
Author(s):  
Doris Stoermer ◽  
Dilrukshi Vitharana ◽  
Niyada Hin ◽  
Greg Delahanty ◽  
Bridget Duvall ◽  
...  
Keyword(s):  
Design Synthesis ◽  
Glutamate Carboxypeptidase Ii ◽  
Pharmacological Evaluation ◽  
Glutamate Carboxypeptidase

S1 pocket of glutamate carboxypeptidase II: A new binding site for amyloid-β degradation

2013 ◽  
Vol 438 (4) ◽  
pp. 765-771 ◽  
Author(s):  
Suk Kyung Lee ◽  
Hyunyoung Kim ◽  
You-Hoon Cheong ◽  
Min-Ju Kim ◽  
Sangmee Ahn Jo ◽  
...  
Keyword(s):  
Binding Site ◽  
Amyloid Β ◽  
Glutamate Carboxypeptidase Ii ◽  
Glutamate Carboxypeptidase

scholarly journals Replication of GWAS-identified neuroblastoma risk loci strengthens the role of BARD1 and affirms the cumulative effect of genetic variations on disease susceptibility

2012 ◽  
Vol 34 (3) ◽  
pp. 605-611 ◽  
Author(s):  
Mario Capasso ◽  
Sharon J. Diskin ◽  
Francesca Totaro ◽  
Luca Longo ◽  
Marilena De Mariano ◽  
...  
Keyword(s):  
Disease Susceptibility ◽  
Cumulative Effect ◽  
Genetic Variations

Structural Insight into the Pharmacophore Pocket of Human Glutamate Carboxypeptidase II⊥

2007 ◽  
Vol 50 (14) ◽  
pp. 3267-3273 ◽  
Author(s):  
Cyril Bařinka ◽  
Miroslava Rovenská ◽  
Petra Mlčochová ◽  
Klára Hlouchová ◽  
Anna Plechanovová ◽  
...  
Keyword(s):  
Glutamate Carboxypeptidase Ii ◽  
Structural Insight ◽  
Glutamate Carboxypeptidase ◽  
Insight Into

scholarly journals Immunotoxicity of Xenobiotics in Fish: A Role for the Aryl Hydrocarbon Receptor (AhR)?

2021 ◽  
Vol 22 (17) ◽  
pp. 9460
Author(s):  
Helmut Segner ◽  
Christyn Bailey ◽  
Carolina Tafalla ◽  
Jun Bo
Keyword(s):  
Immune System ◽  
Aryl Hydrocarbon Receptor ◽  
Disease Susceptibility ◽  
Immune Cell ◽  
Physiological Role ◽  
Immune Gene ◽  
Immune Systems ◽  
Aryl Hydrocarbon ◽  
The Impact

The impact of anthropogenic contaminants on the immune system of fishes is an issue of growing concern. An important xenobiotic receptor that mediates effects of chemicals, such as halogenated aromatic hydrocarbons (HAHs) and polyaromatic hydrocarbons (PAHs), is the aryl hydrocarbon receptor (AhR). Fish toxicological research has focused on the role of this receptor in xenobiotic biotransformation as well as in causing developmental, cardiac, and reproductive toxicity. However, biomedical research has unraveled an important physiological role of the AhR in the immune system, what suggests that this receptor could be involved in immunotoxic effects of environmental contaminants. The aims of the present review are to critically discuss the available knowledge on (i) the expression and possible function of the AhR in the immune systems of teleost fishes; and (ii) the impact of AhR-activating xenobiotics on the immune systems of fish at the levels of immune gene expression, immune cell proliferation and immune cell function, immune pathology, and resistance to infectious disease. The existing information indicates that the AhR is expressed in the fish immune system, but currently, we have little understanding of its physiological role. Exposure to AhR-activating contaminants results in the modulation of numerous immune structural and functional parameters of fish. Despite the diversity of fish species studied and the experimental conditions investigated, the published findings rather uniformly point to immunosuppressive actions of xenobiotic AhR ligands in fish. These effects are often associated with increased disease susceptibility. The fact that fish populations from HAH- and PAH-contaminated environments suffer immune disturbances and elevated disease susceptibility highlights that the immunotoxic effects of AhR-activating xenobiotics bear environmental relevance.

scholarly journals Glutamate Carboxypeptidase II in Aging Rat Prefrontal Cortex Impairs Working Memory Performance

2021 ◽  
Vol 13 ◽  
Author(s):  
Dibyadeep Datta ◽  
Shannon N. Leslie ◽  
Elizabeth Woo ◽  
Nishita Amancharla ◽  
Ayah Elmansy ◽  
...  
Keyword(s):  
Working Memory ◽  
Memory Performance ◽  
Cognitive Disorders ◽  
Glutamate Carboxypeptidase Ii ◽  
Prefrontal Cortical ◽  
Aging Rat ◽  
Medial Pfc ◽  
Improved Performance ◽  
Glutamate Carboxypeptidase ◽  
Pentanedioic Acid

Glutamate carboxypeptidase II (GCPII) expression in brain is increased by inflammation, and reduces NAAG (N-acetyl aspartyl glutamate) stimulation of mGluR3 signaling. Genetic insults in this signaling cascade are increasingly linked to cognitive disorders in humans, where increased GCPII and or decreased NAAG-mGluR3 are associated with impaired prefrontal cortical (PFC) activation and cognitive impairment. As aging is associated with increased inflammation and PFC cognitive deficits, the current study examined GCPII and mGluR3 expression in the aging rat medial PFC, and tested whether GCPII inhibition with 2-(3-mercaptopropyl) pentanedioic acid (2-MPPA) would improve working memory performance. We found that GCPII protein was expressed on astrocytes and some microglia as expected from previous studies, but was also prominently expressed on neurons, and showed increased levels with advancing age. Systemic administration of the GCPII inhibitor, 2-MPPA, improved working memory performance in young and aged rats, and also improved performance after local infusion into the medial PFC. As GCPII inhibitors are well-tolerated, they may provide an important new direction for treatment of cognitive disorders associated with aging and/or inflammation.

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