Thyroid hormone stimulates gamma-glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures.
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.
Dasgupta
Asmita
A
Division of Neurobiology, Indian Institute of Chemical Biology, Jadavpur, Kolkata, India.
Das
Sumantra
S
Sarkar
Pranab Kumar
PK
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D013956:Antithyroid Agents / Q000494:pharmacology; D001253:Astrocytes / Q000187:drug effects* / Q000201:enzymology; D001835:Body Weight / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000201:enzymology / Q000254:growth & development; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D007037:Hypothyroidism / Q000139:chemically induced; D007150:Immunohistochemistry / Q000379:methods; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D011247:Pregnancy; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D013889:Thiouracil / Q000494:pharmacology; D013963:Thyroid Hormones / Q000494:pharmacology*; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D013956:Antithyroid Agents; D004791:Enzyme Inhibitors; D007555:Isoxazoles; D013963:Thyroid Hormones; D013889:Thiouracil; D005723:gamma-Glutamyltransferase; D005978:Glutathione; C006303:acivicin