Price S R, England B K, Bailey J L, Van Vreede K, Mitch W E
Renal Division, Emory University School of Medicine, Atlanta, Georgia 30322.
Am J Physiol. 1994 Oct;267(4 Pt 1):C955-60. doi: 10.1152/ajpcell.1994.267.4.C955.
In rat muscle metabolic acidosis increases ATP-dependent protein degradation and levels of mRNAs for ubiquitin (Ub) and proteasome subunits. Because adrenalectomy (ADX) abolishes the proteolytic response to acidosis in muscle, we examined whether glucocorticoids (GCs) are necessary for acidosis-induced changes in Ub and proteasome mRNAs in muscles. Total RNA content of the white fiber extensor digitorum longus or mixed fiber gastrocnemius muscles were lowest in muscles of ADX rats given acid plus GCs. In contrast, the abundance of Ub and C2 and C9 proteasome subunits mRNAs were increased in muscles from this group compared with untreated ADX rats or ADX rats given acid or GCs alone. Because total RNA is reduced, the increase in these mRNAs in muscles of ADX rats receiving acid plus GCs provides evidence for a specific activation of the ATP-dependent-Ub-proteasome pathway. Thus, GCs are required but not sufficient to produce the coordinated increase in mRNAs encoding ubiquitin and proteasome subunits occurring in muscles of acidotic rats.
在大鼠肌肉中，代谢性酸中毒会增加ATP依赖的蛋白质降解以及泛素（Ub）和蛋白酶体亚基的mRNA水平。由于肾上腺切除术（ADX）消除了肌肉对酸中毒的蛋白水解反应，我们研究了糖皮质激素（GCs）对于酸中毒诱导的肌肉中Ub和蛋白酶体mRNA变化是否必要。给予酸加GCs的ADX大鼠肌肉中，白色纤维的趾长伸肌或混合纤维的腓肠肌的总RNA含量最低。相比之下，与未处理的ADX大鼠或单独给予酸或GCs的ADX大鼠相比，该组大鼠肌肉中Ub以及C2和C9蛋白酶体亚基的mRNA丰度增加。由于总RNA减少，接受酸加GCs的ADX大鼠肌肉中这些mRNA的增加为ATP依赖的泛素-蛋白酶体途径的特异性激活提供了证据。因此，GCs是产生酸中毒大鼠肌肉中编码泛素和蛋白酶体亚基的mRNA协同增加所必需的，但并不充分。
