Bergamini E, Del Roso A, Gori Z, Masiello P, Masini M, Pollera M
Istituto di Patologia Generale, Pisa, Italy.
Am J Physiol. 1994 Jan;266(1 Pt 1):G118-22. doi: 10.1152/ajpgi.1994.266.1.G118.
Regulation of liver macroautophagy and protein degradation by hormones and direct regulatory amino acids were studied in male 2-mo-old Sprague-Dawley albino rats with the use of the antilipolytic agent 3,5'-dimethylpyrazole (DMP; 12 mg/kg body wt ip) as a stimulatory agent. Injection of DMP decreased glutamine plasma levels and glutamine release from the perfused liver. Autophagic vacuoles were observed in the pericanalicular area of liver cells after 30 min. Levels and release of other regulatory amino acids did not exhibit any significant decrease but subsequently increased. Intraperitoneal administration of glutamine inhibited the proteolytic response. In conclusion, these studies demonstrate that in vivo induction and control of liver macroautophagy and protein degradation by the physiological mechanism (i.e., by shortage of nutrients) involve unbalanced and asynchronous changes in the levels of selected direct regulatory amino acids (i.e., a decrease in glutamine and a subsequent increase in leucine and tyrosine levels).
利用抗脂解剂3,5'-二甲基吡唑（DMP；12毫克/千克体重，腹腔注射）作为刺激剂，研究了激素和直接调节性氨基酸对2月龄雄性斯普拉格-道利白化大鼠肝脏巨自噬和蛋白质降解的调节作用。注射DMP可降低血浆谷氨酰胺水平以及灌注肝脏中谷氨酰胺的释放。30分钟后，在肝细胞的胆小管周围区域观察到自噬泡。其他调节性氨基酸的水平和释放未出现任何显著下降，但随后有所增加。腹腔注射谷氨酰胺可抑制蛋白水解反应。总之，这些研究表明，通过生理机制（即营养物质短缺）在体内诱导和控制肝脏巨自噬和蛋白质降解涉及所选直接调节性氨基酸水平的不平衡和异步变化（即谷氨酰胺减少，随后亮氨酸和酪氨酸水平增加）。
