Homozygous deletion of glutathione S-transferase Theta 1 and Mu1 increase the risk of non-syndromic oral clefts in a Mexican population

2021 ◽  
pp. 105246
Author(s):  
Mariana G. Lecourtois-Amézquita ◽  
Betzaida Cuevas-Córdoba ◽  
Juan Santiago-García
Keyword(s):  
Homozygous Deletion ◽  
Mexican Population ◽  
Glutathione S Transferase ◽  
Oral Clefts

scholarly journals Deletion of Ser-171 causes inactivation, proteasome-mediated degradation and complete deficiency of human transaldolase

2004 ◽  
Vol 382 (2) ◽  
pp. 725-731 ◽  
Author(s):  
Craig E. GROSSMAN ◽  
Brian NILAND ◽  
Christina STANCATO ◽  
Nanda M. VERHOEVEN ◽  
Marjo S. van der KNAAP ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Conformational Changes ◽  
Proteasome Inhibitors ◽  
Homozygous Deletion ◽  
Enzymic Activity ◽  
Glutathione S Transferase ◽  
Rapid Degradation ◽  
Reticulocyte Lysates ◽  
H Protein

Homozygous deletion of three nucleotides coding for Ser-171 (S171) of TAL-H (human transaldolase) has been identified in a female patient with liver cirrhosis. Accumulation of sedoheptulose 7-phosphate raised the possibility of TAL (transaldolase) deficiency in this patient. In the present study, we show that the mutant TAL-H gene was effectively transcribed into mRNA, whereas no expression of the TALΔS171 protein or enzyme activity was detected in TALΔS171 fibroblasts or lymphoblasts. Unlike wild-type TAL-H–GST fusion protein (where GST stands for glutathione S-transferase), TALΔS171–GST was solubilized only in the presence of detergents, suggesting that deletion of Ser-171 caused conformational changes. Recombinant TALΔS171 had no enzymic activity. TALΔS171 was effectively translated in vitro using rabbit reticulocyte lysates, indicating that the absence of TAL-H protein in TALΔS171 fibroblasts and lymphoblasts may be attributed primarily to rapid degradation. Treatment with cell-permeable proteasome inhibitors led to the accumulation of TALΔS171 in whole cell lysates and cytosolic extracts of patient lymphoblasts, suggesting that deletion of Ser-171 led to rapid degradation by the proteasome. Although the TALΔS171 protein became readily detectable in proteasome inhibitor-treated cells, it displayed no appreciable enzymic activity. The results suggest that deletion of Ser-171 leads to inactivation and proteasome-mediated degradation of TAL-H. Since TAL-H is a regulator of apoptosis signal processing, complete deficiency of TAL-H may be relevant for the pathogenesis of liver cirrhosis.

scholarly journals GSTT1 Gene Deletion Is Associated with Lung Cancer in Mexican Patients

2004 ◽  
Vol 19 (6) ◽  
pp. 259-261 ◽  
Author(s):  
M. P. Gallegos-Arreola ◽  
B. C. Gómez-Meda ◽  
G. Morgan-Villela ◽  
M. R. Arechavaleta-Granell ◽  
L. Arnaud-López ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Gene Deletion ◽  
Lung Cancer Risk ◽  
Homozygous Deletion ◽  
Glutathione S Transferase ◽  
Gstt1 Null Genotype ◽  
Lung Cancer Patients ◽  
Gstt1 Gene ◽  
Gst Activity

Glutathione S-transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco-derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking.We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty-one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.

scholarly journals Homozygous deletion of gene for glutathione S-transferase M1 in bladder cancer.

BMJ ◽  
1993 ◽  
Vol 307 (6902) ◽  
pp. 481-482 ◽  
Author(s):  
A K Daly ◽  
D J Thomas ◽  
J Cooper ◽  
W R Pearson ◽  
D E Neal ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Homozygous Deletion ◽  
Glutathione S Transferase

Inter-Individual Variation in Levels of the Detoxifying Enzyme Glutathione S-Transferase pi (GSTP1) in Placentas from a Mexican Population

2004 ◽  
Vol 2 (1) ◽  
pp. 41-51
Author(s):  
Penelope Quintana ◽  
Teresa Dodd-Butera ◽  
Carolyn Shaputnic ◽  
Martha Ramirez-Zetina ◽  
Ana Batista ◽  
...  
Keyword(s):  
Individual Variation ◽  
Mexican Population ◽  
Glutathione S Transferase ◽  
Detoxifying Enzyme

Frequency of glutathione S-transferase M1 deletion in smokers with emphysema and lung cancer

1997 ◽  
Vol 16 (7) ◽  
pp. 356-360 ◽  
Author(s):  
DJ Harrison ◽  
AM Cantlay ◽  
F. Rae ◽  
D. Lamb ◽  
Cad Smith
Keyword(s):  
Lung Cancer ◽  
Lung Disease ◽  
Cigarette Smoke ◽  
Lung Tissue ◽  
Odds Ratio ◽  
Homozygous Deletion ◽  
Control Group ◽  
Glutathione S Transferase ◽  
Gstm1 Gene ◽  
Wide Range

1 Genetic variation at the glutathione S-transferase M1 locus (GSTM1) has been associated with a number of apparently unrelated cancers, including lung cancer. Emphysema is a common lung disease often found concomitant with lung cancer. Both emphysema and lung cancer may result from chemical and oxidative damage caused by reactive species present in cigarette smoke or released from neutrophils recruited follow ing cigarette smoke induced injury. GSTM1 may protect against such damage through detoxification of cigarette smoke components. Polymorphism of this gene may thus influence susceptibility not just to lung cancer, but to other forms of lung disease. 2 Resection specimens from a group of 168 lung cancer patients were assessed for the presence of macro scopic centriacinar and panacinar emphysema. DNA was extracted from archival material and genotyped for the GSTM1 polymorphism using the polymerase chain reaction. A control group of 384 anonymous blood donations was used to determine the frequency of the GSTM1 gene deletion in a random control population. Reverse transcription on lung tissue was performed to investigate mRNA expression of GSTM1 and GSTM4. 3 In 57 lung cancer cases with no emphysema there was no association with homozygous deletion of the GSTM1 gene (51% null in cancer and 53% null in control groups). However in 111 patients with emphysema and lung cancer there was an increase in the frequency of deletion (65%, P=0.032) giving an odds ratio of 1.36(0.32-2.40). In 43 cases there was evidence of both centriacinar and panacinar emphy sema. The frequency of GSTM1 deletion was 70% (Odds ratio 2.11, 0.97 - 3.25). Both GSTM1 and GSTM4 mRNAs were expressed in lung tissue. 4 These findings suggest that GSTM1 has a general but rather small protective effect against toxicological injury in the lung which is not specific to cancer. This is of relevance in considering the health effects of exposure to a wide range of reactive chemicals in the environment.

Lamotrigine Use in Pregnancy May Cause Oral Clefts

2006 ◽  
Vol 2 (7) ◽  
pp. 1-14
Author(s):  
ELIZABETH MECHCATIE
Keyword(s):  
Oral Clefts ◽  
In Pregnancy

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome

VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Alejandra María Zúñiga-Muñoz ◽  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Elías Núñez-Garrido ◽  
Rodrigo Velázquez Espejel ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Glutathione S Transferase ◽  
Reduced And Oxidized Glutathione ◽  
Total Antioxidant ◽  
Elevated Activity ◽  
Acute Dissection ◽  
Thoracic Aneurysms

Abstract. Background: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. Patients and methods: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. Results: LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). Conclusions: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

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