title: CaMKII activity is reduced in skeletal muscle during sepsis.
abstract: Exercise-induced muscle hypertrophy is associated with increased calcium/calmodulin-dependent protein kinase II (CaMKII) expression and activity. In contrast, the influence of muscle atrophy-related conditions on CaMKII is poorly understood. Here, we tested the hypothesis that sepsis-induced muscle wasting is associated with reduced CaMKII expression and activity. Sepsis, induced by cecal ligation and puncture in rats, and treatment of rats with TNFα, resulted in reduced total CaMKII activity in skeletal muscle whereas autonomous CaMKII activity was unaffected. The expression of CaMKIIδ, but not β and γ, was reduced in septic muscle. In additional experiments, treatment of cultured myotubes with TNFα resulted in reduced total CaMKII activity and decreased levels of phosphorylated glycogen synthase kinase (GSK)-3β, a downstream target of CaMKII. The present results suggest that sepsis-induced muscle wasting is associated with reduced CaMKII activity and that TNFα may be involved in the regulation of CaMKII activity in skeletal muscle. Decreased phosphorylation (consistent with activation) of GSK-3β may be a consequence of reduced CaMKII activity, indicating that inhibited CaMKII activity may be involved in the catabolic response to sepsis.
authors.affiliation: Department of Surgery, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Zaira
authors.initials: Z
authors.lastname: Aversa
authors.forename: Nima
authors.initials: N
authors.lastname: Alamdari
authors.forename: Estibaliz
authors.initials: E
authors.lastname: Castillero
authors.forename: Maurizio
authors.initials: M
authors.lastname: Muscaritoli
authors.forename: Filippo
authors.initials: F
authors.lastname: Rossi Fanelli
authors.forename: Per-Olof
authors.initials: PO
authors.lastname: Hasselgren
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015870:Gene Expression; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology* / Q000382:microbiology / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000382:microbiology / Q000473:pathology; D010538:Peritonitis / Q000201:enzymology / Q000382:microbiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000201:enzymology*; D026362:Serum Response Factor / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D026362:Serum Response Factor; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D038362:Glycogen Synthase Kinase 3