Growth hormone alters components of the glutathione metabolic pathway in Ames dwarf mice
Growth hormone alters components of the glutathione metabolic pathway in Ames dwarf mice
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DOI：
10.1196/annals.1297.053
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发表时间：
2004-01-01
期刊：
影响因子：
--
通讯作者：
Uthus, EO
中科院分区：
文献类型：
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作者：
Brown-Borg, HM;Rakoczy, SG;Uthus, EO
生长激素（GH）/胰岛素样生长因子-1（IGF-1）/胰岛素途径的信号传导减少与几个物种的寿命延长有关。艾姆斯侏儒小鼠缺乏GH和IGF-1，并且比野生型同窝小鼠（分别为雄性和雌性）寿命长50-64%。以前，我们已经表明，艾姆斯小鼠表现出抗氧化酶水平升高和氧化损伤较低。为了进一步探讨生长激素和抗氧化剂的表达之间的关系，我们管理生长激素或生理盐水侏儒小鼠和谷胱甘肽（GSH）的合成和降解系统的组成部分进行了评估。生长激素治疗显着提高肾脏γ-谷氨酰-半胱氨酸合成酶蛋白水平在3个月和12个月大的侏儒小鼠。相反，GSH降解酶γ-谷氨酰转肽酶的活性在脑（P <0.05）、肾（P <0.01）、心脏（P <0.005）和肝（P <0.06）中被GH给药抑制。解毒酶谷胱甘肽-S-转移酶的活性水平在3月龄和12月龄的肾组织和12月龄的矮小肝组织中也受到抑制（P <0.05）。综上所述，目前的结果沿着与以前的研究数据支持生长激素在调节抗氧化防御，并最终在生物体的寿命与改变生长激素或IGF-1信号。
Reduced signaling of the growth hormone (GH)/insulin-like growth factor-1 (IGF-1)/insulin pathway is associated with extended life span in several species. Ames dwarf mice are GH and IGF-1 deficient and live 50-64% longer than wild-type littermates (males and females, respectively). Previously, we have shown that Ames mice exhibit elevated levels of antioxidative enzymes and lower oxidative damage. To further explore the relationship between GH and antioxidant expression, we administered GH or saline to dwarf mice and evaluated components of the glutathione (GSH) synthesis and degradation system. Growth hormone treatment significantly elevated kidney gammaglutamyl-cysteine synthetase protein levels in 3- and 12-month-old dwarf mice. In contrast, the activity of the GSH degradation enzyme, gamma-glutamyl transpeptidase, was suppressed by GH administration in brain (P < .05), kidney (P < .01), heart (P < .005), and liver (P < .06). Activity levels of the detoxification enzyme, glutathione-S-transferase, were also suppressed in kidney tissues at 3 and 12 months of age and in 12-month-old dwarf liver tissues (P < .05). Taken together, the current results along with data from previous studies support a role for growth hormone in the regulation of antioxidative defense and, ultimately, life span in organisms with altered GH or IGF-1 signaling.