|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Division of Endocrinology and Metabolism, Department of Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
2 Department of Medical Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan
3 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
4 Department of Biochemical Science and Technology, College of Life Science, National Taiwan University, Taipei, Taiwan
* To whom correspondence should be addressed. E-mail: whhsheu{at}vghtc.vghtc.gov.tw.
Hepatic cirrhosis is associated with negative nitrogen balance and loss of lean body
mass. This study aimed to identify the specific proteolytic pathways activated in
skeletal muscles of cirrhotic rats. Tumor necrosis factor-
(TNF-
) can stimulate
muscle proteolysis. Therefore, a potential relationship between TNF-
and muscle
wasting in liver cirrhosis was also evaluated. Cirrhosis was induced by bile duct
ligation (BDL) in male adult Sprague Dawley rats. Messenger RNA (mRNA) and
protein levels of various targets were determined by reverse transcription-polymerase
chain reaction (RT-PCR) and Western blotting, respectively. The proteolytic rate
was measured ex vivo using isolated muscles. Compared with sham-operated
controls, BDL rats had an increased degradation rate of muscle proteins, and
enhanced gene expression of ubiquitin, 14 kDa ubiquitin carrier protein E2, and the
proteasome subunits C2 and C8 (P<0.01). The muscle protein levels of free
ubiquitin and conjugated ubiquitin levels were also elevated (P<0.01). However,
there was no difference between the two groups with regard to cathepsin and calpain
mRNA levels. Cirrhotic muscle TNF-
levels were increased and correlated
positively with free and conjugated ubiquitin (P<0.01). We conclude that the
ubiquitin-proteasome system is involved in muscle wasting of rats with BDL-induced
cirrhosis. TNF-
might play a role in mediating activation of this proteolytic
pathway, probably through a local mechanism.
This article has been cited by other articles:
![]() |
A. M. Baviera, N. M. Zanon, L. C. Carvalho Navegantes, R. H. Migliorini, and I. d. C. Kettelhut Pentoxifylline inhibits Ca2+-dependent and ATP proteasome-dependent proteolysis in skeletal muscle from acutely diabetic rats Am J Physiol Endocrinol Metab, March 1, 2007; 292(3): E702 - E708. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Di Marco, R. Mazroui, P. Dallaire, S. Chittur, S. A. Tenenbaum, D. Radzioch, A. Marette, and I.-E. Gallouzi NF-{kappa}B-Mediated MyoD Decay during Muscle Wasting Requires Nitric Oxide Synthase mRNA Stabilization, HuR Protein, and Nitric Oxide Release Mol. Cell. Biol., August 1, 2005; 25(15): 6533 - 6545. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |