Hickson R C, Wegrzyn L E, Osborne D F, Karl I E
School of Kinesiology, University of Illinois at Chicago 60608-1516, USA.
Am J Physiol. 1996 May;270(5 Pt 1):E912-7. doi: 10.1152/ajpendo.1996.270.5.E912.
Skeletal muscle atrophy from glucocorticoids is prevented by glutamine infusion. Because the gene-encoding glutamine synthetase (GS) is glucocorticoid inducible, it represented an appropriate model for resting whether glucocorticoids and glutamine exert opposing actions on the expression of specific genes related to atrophy in muscle tissue. Rats were administered hydrocortisone 21-acetate or the dosing vehicle (carboxymethyl cellulose) and were infused with saline (Sal) or glutamine (Gln, 240 mM, 0.75 ml/h) for 7 days. Hormone treatment did not significantly lower glutamine levels in fast-twitch white or red regions of the quadriceps. Despite higher serum glutamine concentrations with amino acid infusion [1.52 +/- 0.03 (Gln) vs. 1.20 +/- 0.04 (Sal) mumol/ml], muscle glutamine concentrations were not markedly increased in these fiber types. In saline-infused animals, glucocorticoid treatment produced 200-300% increases in plantaris, fast-twitch white, and fast-twitch red muscle GS enzyme activity and mRNA. Moreover, in all muscle types studied, glutamine infusion diminished glucocorticoid effects on GS enzyme activity to 131-159% and on GS mRNA to 110-200% of the values in saline-treated controls. These data demonstrate that glutamine infusion results in inhibiting GS expression, but the absence of changes in muscle glutamine concentration suggests the interplay of additional regulators of the GS gene.
谷氨酰胺输注可预防糖皮质激素引起的骨骼肌萎缩。由于编码谷氨酰胺合成酶（GS）的基因是糖皮质激素诱导型的，它代表了一个合适的模型，用于探究糖皮质激素和谷氨酰胺是否对与肌肉组织萎缩相关的特定基因表达产生相反的作用。给大鼠注射21 - 醋酸氢化可的松或给药载体（羧甲基纤维素），并输注生理盐水（Sal）或谷氨酰胺（Gln，240 mM，0.75 ml/h），持续7天。激素治疗并未显著降低股四头肌快肌白色或红色区域的谷氨酰胺水平。尽管氨基酸输注后血清谷氨酰胺浓度升高[1.52±0.03（Gln）对1.20±0.04（Sal）μmol/ml]，但这些纤维类型的肌肉谷氨酰胺浓度并未明显增加。在输注生理盐水的动物中，糖皮质激素治疗使跖肌、快肌白色和快肌红色肌肉的GS酶活性和mRNA增加了200 - 300%。此外，在所有研究的肌肉类型中，谷氨酰胺输注将糖皮质激素对GS酶活性的影响降至生理盐水处理对照组的131 - 159%，对GS mRNA的影响降至110 - 200%。这些数据表明，谷氨酰胺输注会抑制GS表达，但肌肉谷氨酰胺浓度没有变化表明GS基因存在其他调节因子的相互作用。
