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Thyroid hormone stimulates γ‐glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures
Author(s) -
Dasgupta Asmita,
Das Sumantra,
Sarkar Pranab Kumar
Publication year - 2005
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.20657
Subject(s) - glutathione , cycloheximide , medicine , endocrinology , hormone , catabolism , oxidative stress , biology , thyroid , homeostasis , enzyme , chemistry , metabolism , biochemistry , protein biosynthesis
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 γ‐glutamyl transpeptidase (γGT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral γGT 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 γGT by 25‐30% within 4–6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of γGT by 30–40% within 4–6 hr. The induction of γGT by TH was blocked by actinomycin D or cycloheximide. γGT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the γGT‐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 γGT by TH and a faster processing of GSH. Because the products of γGT reaction are putative precursors for neuronal GSH, the activation of γGT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. © 2005 Wiley‐Liss, Inc.