Thyroid hormone stimulates γ-glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures
Thyroid hormone stimulates γ-glutamyl transpeptidase in the developing rat cerebra and in astroglial cultures
复制标题
DOI：
10.1002/jnr.20657
复制
发表时间：
2005-12-15
影响因子：
4.2
通讯作者：
Sarkar, PK
中科院分区：
文献类型：
--
作者：
Dasgupta, A;Das, S;Sarkar, PK
发育中的大鼠大脑中的甲状腺功能减退症与氧化应激增强有关，其最早的表现之一是谷胱甘肽（GSH）水平下降。为探讨甲状腺激素（TH）对GSH稳态的作用，研究了TH对GSH催化关键酶γ-谷氨酰转肽酶（γ-GT）的影响。甲状腺功能减退症下降的大脑γ GT的比活性在所有出生后年龄检查（出生后1-20天），最大抑制42%，在出生后第10天。15日龄大鼠腹腔注射TH，4-6小时内γ-GT比活性增加25-30%，TH处理原代培养的星形胶质细胞4 - 6小时内γ-GT比活性增加30-40%，TH对γ-GT的诱导作用可被放线菌素D或放线菌酮阻断。γ GT是一种胞外酶，通常参与星形胶质细胞释放的GSH的催化。在γ GT-抑制剂，阿西维星，GSH释放在星形胶质细胞的培养基中的存在下，线性增加至少6小时和TH没有影响这种积累模式。在不存在阿西维星的情况下，TH处理的细胞的培养基的GSH含量显著低于未处理的对照，这是由于TH激活γ GT和GSH的更快处理。由于γ-GT反应的产物是神经元GSH的假定前体，因此TH激活γ-GT可能有助于神经元中GSH的合成及其对氧化应激的保护。(c)2005 Wiley-Liss，Inc.
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 (gamma GT), the key enzyme involved in the catalysis of GSH, was studied. Hypothyroidism declined the specific activity of cerebral gamma GT 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 gamma GT by 25-30% within 4-6 hr. Treatment of primary cultures of astrocytes by TH also enhanced the specific activity of gamma GT by 30-40% within 4-6 hr. The induction of gamma GT by TH was blocked by actinomycin D or cycloheximide. gamma GT is an ectoenzyme that is normally involved in the catabolism of GSH released by astrocytes. In the presence of the gamma GT-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 gamma GT by TH and a faster processing of GSH. Because the products of gamma GT reaction are putative precursors for neuronal GSH, the activation of gamma GT by TH may be conducive to GSH synthesis in neurons and their protection from oxidative stress. (c) 2005 Wiley-Liss, Inc.