Thyroid hormone stimulates γ‐glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures

Abstract

Hypothyroidism in the developing rat brain is associated with enhanced oxidative stress, one of the earliest manifestations of which is a decline in the level of glutathione (GSH). To investigate the role of thyroid hormone (TH) on GSH homeostasis, the effect of TH on gamma-glutamyl transpeptidase (gammaGT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral gammaGT at all postnatal ages examined (postnatal day 1-20) with a maximum inhibition of 42% at postnatal day 10. Intraperitoneal injection of TH to 15-day-old rat pups increased the specific activity of gammaGT by 25-30% within 4-6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of gammaGT by 30-40% within 4-6 hr. The induction of gammaGT by TH was blocked by actinomycin D or cycloheximide. gammaGT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the gammaGT-inhibitor, acivicin, GSH released in the culture medium of astrocytes increased linearly for at least 6 hr and TH had no effect on this accumulation pattern. In the absence of acivicin, GSH content of the medium from TH-treated cells was significantly lower than that of untreated controls due to activation of gammaGT by TH and a faster processing of GSH. Because the products of gammaGT reaction are putative precursors for neuronal GSH, the activation of gammaGT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress.

Aging is associated with dimerization and inactivation of the brain-enriched tyrosine phosphatase STEP

“…To determine GSH levels following DEM or H 2 O 2 treatment, HEK293 cells were washed twice with PBS, scraped with 0.1ml 2.5% SSA, incubated for 10 min on ice and then centrifuged at 13,000 rpm for 10 min (Dasgupta et al, 2005). The supernatant was used for GSH assay as described above.…”

Docosahexaenoic acid facilitates cell maturation and β-adrenergic transmission in astrocytes

“…Additionally, lactate dehydrogenase (LDH) assay was also used to analyze cell viability using a protocol published previously (30). Briefly, after treatment with the FAs, 10 ml of the medium was added to 190 ml of 80 mM Tris-HCl buffer, pH 7.2, containing 200 mM NaCl in the well of a microtiter plate.…”

Gestational Prooxidant-Antioxidant Imbalance may be at Higher Risk for Postpartum Thyroid Disease

“…More so, a progressive hypothyroidism during the postnatal period led to a decrease in the levels of total thiol (t-SH) [5,6] and glutathione (GSH) [36,37] and in the activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) associated with an increase in the levels of nitric oxide (NO) [5,6], hydrogen peroxide (H2O2) [38] protein carbonyl (PCa), LPO [36,38] and hydroxyl radical (·OH) [2,36]. These disorders caused oxidative stress [5,6,39]. On the other hand, hypothyroidism is associated with cellular ionic imbalance, augmented oxidative stress, and decreased GSH and glutathione-Stransferase (GST) [2,5,6,[39][40][41].…”

“…These disorders caused oxidative stress [5,6,39]. On the other hand, hypothyroidism is associated with cellular ionic imbalance, augmented oxidative stress, and decreased GSH and glutathione-Stransferase (GST) [2,5,6,[39][40][41]. Also, a reduction in the levels of free radical is predictable on account of the metabolic inhibition by the hypothyroid state [42][43][44].…”