The present study examines whether and to what extent the profiles of proteolytic-related genes are altered in atrophying muscle during prolonged food deprivation. Long-term fasted animals exhibited three metabolic phases characterized by changes in lipid and protein utilization. Starvation induced an increase in some proteolytic gene expressions during P2 of fasting, especially for Cat L (by 3-fold). In P3, the fasting-induced enhancement of mRNA expression involved all proteolytic pathways and was much more pronounced than in P2 for pUb, E2(14k), CAPN3, and Cat B, D, and H (by 2- to 4-fold), for C2, C5, and S5a, (by 5- to 6-fold), and mainly for Cat L, C3, and C8 (by 10- to 15-fold). At the molecular level, it is concluded that the three proteolytic systems found in skeletal muscle are selectively induced in P2 of fasting and coordinately upregulated in late fasting. (C) 2003 Elsevier Inc. All rights reserved.