TY - JOUR
T1 - Selective downregulation of ubiquitin conjugation cascade mRNA occurs in the senescent rat soleus muscle
AU - DeRuisseau, Keith C.
AU - Kavazis, Andreas N.
AU - Powers, Scott K.
N1 - Funding Information:
This work was supported by a grant from the National Institutes of Health (R01 HL62361) awarded to S.K. Powers and the American Lung Association of Florida Research Training Fellowship awarded to K.C. DeRuisseau.
PY - 2005/6
Y1 - 2005/6
N2 - Aging-related alterations of the ubiquitin proteasome pathway (UPP) have been reported in locomotor skeletal muscle. Specifically, declines in proteasome activity have been observed in the soleus of senescent animals compared to the soleus of young controls. However, the influence of aging on the mRNA levels of key components within the ubiquitin conjugation cascade (UCC) remains unknown. We hypothesized that aged soleus muscle would exhibit downregulated expression of select UCC mRNA and decreased levels of ubiquitin-protein conjugates. To test this postulate, we harvested soleus muscles from 6 and 24-26 month old Fisher 344 rats. Aging resulted in a decline in mRNA expression of two key UCC components in soleus muscle; ubiquitin conjugating enzyme E214k (E214k) and muscle ring finger-1 (MuRF1). Surprisingly, no age-related differences existed in the total content of endogenous ubiquitin-protein conjugates in the soleus muscle. Nonetheless, a selective decrease in the level of ubiquitin-protein conjugates (∼30 kDa) was detected in the soleus of senescent animals. These results indicate that the soleus muscle displays a differential mRNA response of select UCC components to aging. Furthermore, the decline in E214k and MuRF1 mRNA levels may contribute to altered substrate degradation by the UCC in the soleus muscle of senescent rats.
AB - Aging-related alterations of the ubiquitin proteasome pathway (UPP) have been reported in locomotor skeletal muscle. Specifically, declines in proteasome activity have been observed in the soleus of senescent animals compared to the soleus of young controls. However, the influence of aging on the mRNA levels of key components within the ubiquitin conjugation cascade (UCC) remains unknown. We hypothesized that aged soleus muscle would exhibit downregulated expression of select UCC mRNA and decreased levels of ubiquitin-protein conjugates. To test this postulate, we harvested soleus muscles from 6 and 24-26 month old Fisher 344 rats. Aging resulted in a decline in mRNA expression of two key UCC components in soleus muscle; ubiquitin conjugating enzyme E214k (E214k) and muscle ring finger-1 (MuRF1). Surprisingly, no age-related differences existed in the total content of endogenous ubiquitin-protein conjugates in the soleus muscle. Nonetheless, a selective decrease in the level of ubiquitin-protein conjugates (∼30 kDa) was detected in the soleus of senescent animals. These results indicate that the soleus muscle displays a differential mRNA response of select UCC components to aging. Furthermore, the decline in E214k and MuRF1 mRNA levels may contribute to altered substrate degradation by the UCC in the soleus muscle of senescent rats.
KW - Locomotor skeletal muscle
KW - Postural muscle
KW - Ubiquitin ligase
KW - Ubiquitin proteasome pathway
KW - Ubiquitin-protein conjugates
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U2 - 10.1016/j.exger.2005.04.005
DO - 10.1016/j.exger.2005.04.005
M3 - Article
C2 - 15963672
AN - SCOPUS:21244450623
SN - 0531-5565
VL - 40
SP - 526
EP - 531
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 6
ER -