SEPSIS IS ASSOCIATED WITH INCREASED MESSENGER-RNAS OF THE UBIQUITIN-PROTEASOME PROTEOLYTIC PATHWAY IN HUMAN SKELETAL-MUSCLE

Previous studies provided evidence that sepsis-induced muscle proteoly sis in experimental animals is caused by increased ubiquitin-proteasom e-dependent protein breakdown. It is not known if a similar mechanism accounts for muscle proteolysis in patients with sepsis. We determined mRNA levels for ubiquitin and the 20 S proteasome subunit HC3 by Nort hern blot analysis in muscle tissue from septic (n = 7) and non-septic (n = 11) patients. Plasma and muscle amino acid concentrations and co ncentrations in urine of 3-methylhistidine (3-MH), creatinine, and cor tisol were measured at the time of surgery to assess the catabolic sta te of the patients. A three- to fourfold increase in mRNA levels for u biquitin and HC3 was noted in muscle tissue from the septic patients c oncomitant with increased muscle levels of phenylalanine and 3-MH and reduced levels of glutamine. Total plasma amino acids were decreased b y similar to 30% in the septic patients. The 3-MH/creatinine ratio in urine was almost doubled in septic patients. The cortisol levels in ur ine were higher in septic than in control patients but this difference did not reach statistical significance. The results suggest that seps is is associated with increased mRNAs of the ubiquitin-proteasome path way in human skeletal muscle.