CaMKII Protein Expression and Phosphorylation in Mouse Skeletal Muscle Following Atrophy and Hypertrophy

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)
Brett Williams (Creator)
East Carolina University (ECU )
Web Site:
Carol A. Witczak

Abstract: The maintenance of skeletal muscle mass is vital for life and elucidation of the molecular mechanisms that control this process is a critical first step towards the development of pharmaceutical treatments for muscle wasting disorders. Intracellular Ca²⁺ is a regulator of muscle growth yet surprisingly the signaling proteins by which Ca²⁺ regulates this function remain largely unknown. The serine/threonine kinase Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) is one of the Ca²⁺-regulated proteins found in muscle. The goal of this study was to determine whether the phosphorylation or protein expression of any of the CaMKII isoforms present in skeletal muscle (i.e. CaMKII[beta]M [gamma] or [delta]) is altered in response to muscle atrophy or hypertrophy. Male CD-1 mice (~6-8 weeks old) underwent unilateral denervation of the hindlimb to induce atrophy and the plantaris muscles removed 1 3 7 10 and 14 days later. In addition mice underwent unilateral ablation of the gastrocnemius and soleus muscles to induce hypertrophy and the plantaris muscles removed 1 3 7 and 10 days later. Consistent with previous studies denervation induced a time-dependent decrease in muscle weight after 3 days and ablation induced a time-dependent increase in muscle weight after 3 days. To assess alterations in CaMKII (Thr286/287) phosphorylation and expression western blot analyses were performed. Denervation elicited a significant decrease in CaMKII[beta]M expression after 3 days but an increase in CaMKII[gamma] and CaMKII[delta] after 10 days. Phosphorylation of CaMKII[gamma] was decreased after 7 days while there were no alterations in CaMKII[beta]M or CaMKII[delta]. Ablation induced a significant decrease in CaMKII[beta]M expression after 7 days an increase in CaMKII[delta] after 7 days but no change in CaMKII[gamma]. Phosphorylation of CaMKII[gamma] was significantly decreased after 1 day while there were no changes in CaMKII[beta]M or CaMKII[delta]. Collectively these results suggest a differential and complex regulation of CaMKII isoforms during alterations in muscle mass. In summary this study demonstrated that in mouse skeletal muscle CaMKII isoforms are differentially phosphorylated and expressed during denervation-induced atrophy and synergist ablation-induced hypertrophy. These findings underscore the necessity of examining each CaMKII isoform separately in order to determine its possible role in regulating muscle mass.

Additional Information

Date: 2012
Physiology, Biology, Molecular biology, Atrophy, Calmodulin, CaMKII, Hypertrophy
Protein kinases
Muscular atrophy

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