Activation of the ubiquitin pathway in rat skeletal muscle by
catabolic doses of glucocorticoids.
Auclair;, Daniel, Dominique R. Garrel; A. Chaouki Zerouala; Louis H.
Ferland.
Centre de Recherche, H[circumflex]otel-Dieu de Montr[acute]eal,
Montr[acute]eal, QC, Canada H2W 1T8, D[acute]epartement de nutrition
(D.A., D.R.G. L.H.F.), Universit[acute]e de Montr[acute]eal,
Montr[acute]eal, QC, Canada
APStracts 3:0337C, 1996.
To evaluate whether catabolic levels of glucocorticoids activate the
ubiquitin pathway in conjunction to their known proteolytic effect in
skeletal muscle, rats were injected daily with corticosterone (CTC;
10mg/100g b.w.) for 7 days. Two peaks of urinary excretion of 3
-methylhistidine (3-MH), a specific marker of myofibrillar
proteolysis, were observed at days 1 and 3 (165 and 295% of controls,
respectively). Levels of ubiquitin pathway mRNAs in skeletal muscle
were assessed around the 3-MH peaks. In the EDL, a first rise of two
polyubiquitin (pUb) mRNAs was seen at day 1 (183% and 162% of control
for the UbB and UbC transcripts, respectively, p<0.01). An
accumulation of both E2-14k mRNAs (140%, p<0.02, and 157% of
controls, p<0.01) and proteasome C8 subunit mRNA (222% of
control, p<0.05) was seen at day 2 . A second, more important
peak of induction of pUb mRNA was seen at day 3 (251% and 217% of
controls, for the UbB and UbC transcripts, respectively,
p<0.001). All transcripts returned to near control levels by
day 4. In the soleus, induction of E2-14k mRNA started at day 3 and
reached 216% and 208% of controls at day four (p<0.001), while
an increase of pUb mRNA was observed at days 3 (213% and 241%,
p<0.05) and 4 (211% and 221%, p<0.001). A rise of
proteasome C8 subunit mRNA accumulation was also seen in the soleus
at days 3 (217%, p<0.05) and 4 (157%, p<0.05). Reduced
ubiquitin conjugate levels, possibly due to their rapid degradation
through increased proteasome activity, were observed in both muscle
types at day 3. The parallel between the catabolic effects of CTC and
activation of the ubiquitin pathway in muscles of CTC-treated rats
strongly suggests the involvement of this system in glucocorticoid
-induced muscular atrophy.
Received 6 November 1995; accepted in final form 1 October 1996.
APS Manuscript Number C666-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 13 November 1996