Abstract
Several lines of evidence suggest that the ubiquitin-proteasome pathway is involved in sepsis-induced muscle catabolism. The gene expression of ubiquitin and several of the proteasome subunits was increased in muscle from both septic rats and patients. In other studies, the activity of isolated 20S proteasomes was stimulated in septic muscles. Sepsis-induced increase in muscle total and myofibrillar protein breakdown was inhibited with specific proteasome blockers. Although the ubiquitin-proteasome pathway is upregulated in septic muscle, it is still unclear how the myofibrillar proteins actin and myosin are ubiquitinated and become substrates for the 26S proteasome. Recent studies suggest that a calcium-dependent, calpain-mediated process releases myofilaments from the Z-disks during sepsis. It is possible that this process exposes destabilizing N-terminal residues on actin and myosin, making them suitable substrates for the N-end rule pathway involving the 14 kD ubiquitin-conjugating enzyme E214k and the ubiquitin-protein ligase E3α.
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Sax HC, Talamini MA, Hasselgren PO, Rosenblum L, Ogle CK & Fischer JE (1988) J. Surg. Res. 44: 109–116
Newsholme EA & Parry Billings M (1992) J. Parent. Nutr. 14: 63S–67S
Windmueller HG & Spaeth AE (1980) J. Biol. Chem. 255: 107–112
Reid WD & MacGowan NA (1998) Mol. Cell. Biochem. 179: 63–80
Hasselgren PO (1993) Protein Metabolism in Sepsis. RG Landes Co, Austin, Texas
Attaix D & Taillandier D (1998) Adv. Mol. Cell. Biol. 27: 235–266
Tiao G, Fagan JM, Samuels N, James JH, Hudson K, Lieberman M, Fischer JE & Hasselgren PO (1994) J. Clin. Invest. 94: 2255–2264
Hasselgren PO, James JH, Benson DW, Hall-Angerå s M, Angerå s U, Hiyama DT, Li S & Fischer JE (1989) Metabolism 38: 634–640
Voisin L, Breuille D, Combarret L, Pouyet C, Taillandier D, Aurousseau E, Obled C & Attaix D (1996) J. Clin. Invest. 97: 1610–1617
Fang CH, Tiao G, James H, Ogle C, Fischer JE & Hasselgren PO (1995) J. Am. Coll. Surg. 180: 161–170
Li JB & Goldberg AL (1976) Am. J. Physiol. 231: 441–448
Kettelhut IC, Wing SS & Goldberg AL (1988) Diabetes Metab. Rev. 4: 751–772
Tiao G, Lieberman M, Fischer JE & Hasselgren PO (1997) Am. J. Physiol. 272: R849–R856
Hershko A & Ciechanover A (1992) Annu. Rev. Biochem. 61: 761–807
Wing SS & Banville D (1994) Am. J. Physiol. 267: E39–E48
Hobler SC, Wang JJ, Williams AB, Melandri F, Sun X, Fischer JE & Hasselgren PO (1998) Am. J. Physiol. in press
Tiao G, Fagan J, Roegner V, Lieberman M, Wang JJ, Fischer JE & Hasselgren PO (1996) J. Clin. Invest. 97: 339–348
Lee DH & Goldberg AL (1998) Trends Cell. Biol. 8: 397–403
Hobler SC, Tiao G, Fischer JE, Monaco J & Hasselgren PO (1998) Am. J. Physiol. 274: R30–37
Fenteany G, Standaert RF, Lane WS, Choi S, Corey EJ & Schreiber SL (1995) Science 268: 726–731
Tawa NE, Odyssey R & Goldberg AL (1997) J. Clin. Invest. 100: 197–203
Fang CH, Wang JJ, Hobler S, Li BG, Fischer JE & Hasselgren PO (1998) Clin Sci 95: 225–233
Dick L, Cruikshank AA, Grenier L, Melandri FD, Nunes SL & Stein R (1996) J. Biol. Chem. 271: 7273–7276
Tiao G, Hobler S, Wang JJ, Meyer TA, Luchette FA, Fischer JE & Hasselgren PO (1997) J. Clin. Invest. 99: 163–168
Mansoor O, Beaufrere B, Boirie Y, Ralliere C, Taillandier D, Aurousseau E, Schoeffler P, Arnal M & Attaix D (1996) Proc. Natl. Acad. Sci. USA 93: 2714–2718
Llovera M, Garcia-Martinez C, Argell N, Lopez-Scriano FJ, Authier FJ, Gherardi PK, Argiles JM (1998) Int. J. Mol. Med. 2: 69–73
Auclair D, Garrel DR, Zerouala AC & Ferland LH (1997) Am. J. Physiol. 272: C1007–C1016
Wing SS & Goldberg AL (1993) Am. J. Physiol. 264: E668–E676
Ralliere C, Tauveron I, Taillandier D, Guy L, Boiteux JP, Giraud B, Attaix D & Thieblot P (1997) J. Clin. Endocrinol. Metab. 82: 3161–3164
Roberts RG, Redfern CPF & Goodskip THJ (1996) Fourth International Symposium on Amino Acid/Protein Metabolism in Health and Disease. Padova, Italy, April 12- 13 (abstr)
Mitch WE, Medina R, Grieber S, May RC, England BK, Price SR, Bailey JL & Goldberg AL (1994) J. Clin. Invest. 93: 2127–2133
Bailey JL, Wang W, Engsland BK, Price SR, Ding X & Mitch WE (1996) J. Clin. Invest. 97: 1447–1453
Madura K, Dohmen RJ & Varshavsky A (1993) J. Biol. Chem. 268: 12046–12054
Varshavsky A (1997) Genes to Cells 2: 13–28
Kwon YT, Reiss Y, Fried VA, Hershko A, Yoon JK, Gonda DK, Sangan P, Copeland NG, Jenkins NA & Varshavsky A (1998) Proc. Natl. Acad. Sci. USA 95: 7898–7903
Solomon V, Lecker SH & Goldberg AL (1998) J. Biol. Chem. 273: 25216–25222
Solomon V, Baracos V, Sarraf P & Goldberg AL (1998) Proc. Natl. Acad. Sci. USA 95: 12602–12607
Williams AB, Fischer JE & Hasselgren PO (1998) Surg. Forum 49: 66–69
Dahlmann B, Rutschmann M & Reinauer H (1986) Biochem. J. 234: 659–664.