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Thyroid Hormone Promotes Glutathione Synthesis in Astrocytes by up Regulation of Glutamate Cysteine Ligase Through Differential Stimulation of its Catalytic and Modulator Subunit mRNAs

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Title Thyroid Hormone Promotes Glutathione Synthesis in Astrocytes by up Regulation of Glutamate Cysteine Ligase Through Differential Stimulation of its Catalytic and Modulator Subunit mRNAs
 
Creator Dasgupta, Asmita
Das, Sumantra
Sarkar, Pranab K
 
Subject Cell Biology & Physiology
 
Description To elucidate how thyroid hormone (TH) modulates glutathione (GSH) biogenesis in developing brain, the effect of the hormone on the activity
of glutamate cysteine ligase (GCL), previously known as gamma-glutamyl synthetase (γ-GCS), has been investigated. Hypothyroidism in
developing rat brain declined the activity of GCL. Conversely, administration of TH to hypothyroid rats elicited an increase in the activity of the
enzyme. TH treatment of astrocytes resulted in a rapid increase in the level of GSH and this up regulation was completely inhibited by
L-buthionine S,R-sulfoximine. Kinetics of induction of GCL by TH in astrocytes were closely parallel to that of GSH and the induction was
sensitive to both cycloheximide and actinomycin D. Quantitative RT-PCR analysis revealed that astrocytes contained a basal excess of GCLC
(catalytic subunit of GCL) mRNA, relative to GCLM (modulator subunit of GCL) mRNA, the ratio being 4:1. TH treatment led to a differential
increase in the expression of these two mRNAs, which resulted in a decline in the stoichiometric ratio of GCLC:GCLM mRNA that may favor
holoenzyme formation with enhanced catalytic efficiency. TH treatment improved the antioxidative defense in astrocytes by enhancing their
hydrogen peroxide scavenging ability with a decrease in peroxide half-life from 7.4 to 4.2 min. The overall results suggest that TH plays a positive
role in maintaining GSH homeostasis in astrocytes and in protecting the brain from oxidative stress.
 
Date 2007
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1038/1/2007%2DFRBM.pdf
Dasgupta, Asmita and Das, Sumantra and Sarkar, Pranab K (2007) Thyroid Hormone Promotes Glutathione Synthesis in Astrocytes by up Regulation of Glutamate Cysteine Ligase Through Differential Stimulation of its Catalytic and Modulator Subunit mRNAs. Free Radical Biology & Medicine, 42. pp. 617-626.
 
Relation http://dx.doi.org/10.1016/j.freeradbiomed.2006.11.030
http://www.eprints.iicb.res.in/1038/