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Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease.

ABSTRACT: GSTs are a family of inducible phase II enzymes that may play a neuroprotective role in Parkinson's disease (PD). GSTs may also modify PD risk by metabolizing compounds in cigarettes, as cigarette smoking is generally found to be associated with a decrease in PD risk. Using a population-based case-control study design, we examined polymorphisms of the mu, omega, pi, and theta classes of GST to elucidate the main effects and smoking-GST interactions on PD risk. From three rural California counties, we recruited 289 incident idiopathic PD cases, clinically confirmed by our study neurologist, and 270 population controls, marginally matched by age, gender, and race. We assessed main gene polymorphism associations and evaluated interactions between smoking and GST polymorphisms as departures from a multiplicative scale adjusting for age, gender, and race. We also restricted analyses to Caucasian subjects to address the potential for population stratification (n=235 cases, 220 controls). Among Caucasians, we observed a risk reduction in subjects carrying at least one variant allele for GSTO1 (OR=0.68, 95% CI: 0.47-0.98) and also GSTO2 (OR=0.64, 95% CI: 0.44-0.93); both genes were in strong linkage disequilibrium. No main gene effects were observed for the remaining polymorphisms. We noted a multiplicative interaction between ever having smoked regularly and GSTO1 (OR(interaction)=0.55, 95% CI: 0.33-0.92) and GSTO2 (OR(interaction)=0.54, 95% CI: 0.32-0.90). Results were similar when combining all races. These findings and the paucity of similar studies suggest a need for further inquiry into the association between GSTs, smoking, and PD risk.

SUBMITTER: Wahner AD

PROVIDER: S-EPMC1864949 | biostudies-literature | 2007 Feb

REPOSITORIES: biostudies-literature

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Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease.

Wahner Angelika D AD Glatt Charles E CE Bronstein Jeff M JM Ritz Beate B

Neuroscience letters 20061227 3

GSTs are a family of inducible phase II enzymes that may play a neuroprotective role in Parkinson's disease (PD). GSTs may also modify PD risk by metabolizing compounds in cigarettes, as cigarette smoking is generally found to be associated with a decrease in PD risk. Using a population-based case-control study design, we examined polymorphisms of the mu, omega, pi, and theta classes of GST to elucidate the main effects and smoking-GST interactions on PD risk. From three rural California countie ...[more]

PMID: 17194543

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Project description:Chloroplasts are organelles subjected to extreme oxidative stress conditions. Biomolecules produced in the chloroplasts act as signals guiding plant metabolism toward stress tolerance and play a major role in regulating gene expression in the nucleus. Herein, we used transplastomic plants as an alternative approach to expression of transgenes in the nucleus for conferring stress tolerance to abiotic stresses and herbicides. To investigate the morphophysiological and molecular mechanisms and the role of plastid expressed GSTs in tobacco stress detoxification and stress tolerance, we used transplastomic tobacco lines overexpressing a theta class glutathione transferase (GST) in chloroplasts. The transplastomic plants were tested under drought (0, 100, and 200 mM mannitol) and salinity (0, 150, and 300 mM NaCl) in vitro, and under herbicide stress (Diquat). Our results suggest that pt AtGSTT lines were tolerant to herbicide-induced oxidative and salinity stresses and showed enhanced response tolerance to mannitol-induced osmotic stress compared to WT plants. Overexpression of the Arabidopsis thaliana AtGSTT in the chloroplasts resulted in enhanced photo-tolerance and turgor maintenance under stress. Whole-genome transcriptome analysis revealed that genes related to stress tolerance, were upregulated in pt AtGSTT2a line under both control and high mannitol stress conditions. Transplastomic plants overexpressing the pt AtGSTT2a in the chloroplast showed a state of acclimation to stress, as only limited number of genes were upregulated in the pt AtGSTT2a transplastomic line compared to WT under stress conditions while at the same time genes related to stress tolerance were upregulated in pt AtGSTT2a plants compared to WT in stress-free conditions. In parallel, the metabolic profile indicated limited perturbations of the metabolic homeostasis in the transplastomic lines and greater accumulation of mannitol, and soluble sugars under high mannitol stress. Therefore, transplastomic lines seem to be in a state of acclimation to stress under stress-free conditions, which was maintained even under high mannitol stress. The results help to elucidate the role of GSTs in plant abiotic stress tolerance and the underlying mechanisms of the GSTs expressed in the chloroplast, toward environmental resilience of cultivated crops.

Dataset Information

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease.

Publications

Glutathione S-transferase mu, omega, pi, and theta class variants and smoking in Parkinson's disease.

Similar Datasets

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