RGD Reference Report - Thyroid hormone promotes glutathione synthesis in astrocytes by up regulation of glutamate cysteine ligase through differential stimulation of its catalytic and modulator subunit mRNAs. - Rat Genome Database

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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.

Authors: Dasgupta, A  Das, S  Sarkar, PK 
Citation: Dasgupta A, etal., Free Radic Biol Med. 2007 Mar 1;42(5):617-26. Epub 2006 Dec 15.
RGD ID: 10402376
Pubmed: PMID:17291985   (View Abstract at PubMed)
DOI: DOI:10.1016/j.freeradbiomed.2006.11.030   (Journal Full-text)

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 (gamma-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.




Biological Process

  
Object Symbol
Species
Term
Qualifier
Evidence
With
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Original Reference(s)
GclcRatcellular response to thyroxine stimulus  IEP  RGD 
GclmRatcellular response to thyroxine stimulus  IEP  RGD 


Genes (Rattus norvegicus)
Gclc  (glutamate-cysteine ligase, catalytic subunit) Gclm  (glutamate cysteine ligase, modifier subunit)