Amelioration of denervation-induced atrophy by clenbuterol is associated with increased PKC-alpha activity.
Rat soleus muscle was denervated for 3 or 7 days, and total membrane protein kinase C (PKC) activity and translocation and immunocytochemical localization of PKC isoforms were examined. Dietary administration of clenbuterol concomitant with denervation ameliorated the atrophic response and was associated with increased membrane PKC activity at both 3 (140%) and 7 (190%) days. Of the five PKC isoforms (alpha, epsilon, theta, zeta, and mu) detected in soleus muscle by Western immunoblotting, clenbuterol treatment affected only the PKC-alpha and PKC-theta forms. PKC-alpha was translocated to the membrane fraction upon denervation, and the presence of clenbuterol increased membrane-bound PKC-alpha and active PKC-alpha as assayed by Ser(657) phosphorylation. PKC-theta protein was downregulated upon denervation, and treatment with clenbuterol further decreased both cytosolic and membrane levels. Immunolocalization of PKC-theta showed differences for regulatory and catalytic domains, with the latter showing fast-fiber type specificity. The results suggest potential roles of PKC-alpha and PKC-theta in the mechanism of action of clenbuterol in alleviating denervation-induced atrophy.
Sneddon
A A
AA
The Rowett Research Institute, Bucksburn, Aberdeen, Scotland AB21 9SB. aas@rri.sari.ac.uk
Delday
M I
MI
Maltin
C A
CA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002976:Clenbuterol / Q000494:pharmacology*; D003714:Denervation; D005455:Fluorescent Antibody Technique; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D009133:Muscular Atrophy / Q000209:etiology* / Q000473:pathology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha; D051381:Rats; D011919:Rats, Inbred Strains; D013347:Subcellular Fractions / Q000201:enzymology
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D002976:Clenbuterol