Department of Physical Medicine and Rehabilitation, University of Minnesota, 420 Delaware Street SE, Minneapolis, MN 55455, USA.
J Gerontol A Biol Sci Med Sci. 2010 Feb;65(2):129-37. doi: 10.1093/gerona/glp194. Epub 2009 Dec 16.
This study investigated the mechanisms responsible for the disrupted homeostasis of reduced glutathione (GSH) in aging muscles with stress (14 days of hind-limb unloading [HU]). Adult and old rats were randomized into four groups: weight bearing and 3, 7, and 14 days of HU. Soleus muscles were harvested to investigate the activity or content of enzymes involved in GSH metabolism (utilization and synthesis). The activities of glutathione S transferase, glutathione reductase, gamma-glutamyl transpeptidase, and glutamate cysteine ligase (GCL) were determined. The protein content of the two subunits of GCL, catalytic subunit (GCLC) and modifier subunit (GCLM), were evaluated. The major results, failure to maintain the accelerated GCLC production and GCL activity, are associated with the GSH depletion in aging muscles with 14 days of HU. The results suggest that the regulation of GCL, especially the catalytic subunit, with stress may be compromised in aging muscles.
本研究旨在探究在应激状态下(14 天的后肢去负荷[HU]),衰老肌肉中还原型谷胱甘肽(GSH)稳态失调的机制。成年和老年大鼠被随机分为四组:承重组和 3、7、14 天 HU 组。采集比目鱼肌,研究参与 GSH 代谢(利用和合成)的酶的活性或含量。测定谷胱甘肽 S 转移酶、谷胱甘肽还原酶、γ-谷氨酰转肽酶和谷氨酸半胱氨酸连接酶(GCL)的活性。评估 GCL 的两个亚基,即催化亚基(GCLC)和调节亚基(GCLM)的蛋白含量。主要结果是,在 14 天 HU 的衰老肌肉中,GCLC 加速产生和 GCL 活性未能维持,这与 GSH 的耗竭有关。结果表明,GCL 的调节,特别是催化亚基,可能在衰老肌肉中受到应激的影响而受到损害。