title: L-Carnitine: a potential treatment for blocking apoptosis and preventing skeletal muscle myopathy in heart failure.
abstract: Skeletal muscle in congestive heart failure is responsible for increased fatigability and decreased exercise capacity. A specific myopathy with increased expression of fast-type myosins, myocyte atrophy, secondary to myocyte apoptosis triggered by high levels of circulating tumor necrosis factor-alpha (TNF-alpha) has been described. In an animal model of heart failure, the monocrotaline-treated rat, we have observed an increase of apoptotic skeletal muscle nuclei. Proapoptotic agents, caspase-3 and -9, were increased, as well as serum levels of TNF-alpha and its second messenger sphingosine. Treatment of rats with L-carnitine, known for its protective effect on muscle metabolism injuries, was found to inhibit caspases and to decrease the levels of TNF-alpha and sphingosine, as well as the number of apoptotic myonuclei. Staurosporine was used in in vitro experiments to induce apoptosis in skeletal muscle cells in culture. When L-carnitine was applied to skeletal muscle cells, before staurosporine treatment, we observed a reduction in apoptosis. These findings show that L-carnitine can prevent apoptosis of skeletal muscles cells and has a role in the treatment of congestive heart failure-associated myopathy.
authors.affiliation: Internal Medicine, City Hospital, 45011 Adria, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Vescovo
authors.forename: Barbara
authors.initials: B
authors.lastname: Ravara
authors.forename: Valerio
authors.initials: V
authors.lastname: Gobbo
authors.forename: Marco
authors.initials: M
authors.lastname: Sandri
authors.forename: Annalisa
authors.initials: A
authors.lastname: Angelini
authors.forename: Mila
authors.initials: M
authors.lastname: Della Barbera
authors.forename: Massimo
authors.initials: M
authors.lastname: Dona
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Peluso
authors.forename: Menotti
authors.initials: M
authors.lastname: Calvani
authors.forename: Luigi
authors.initials: L
authors.lastname: Mosconi
authors.forename: Luciano
authors.initials: L
authors.lastname: Dalla Libera
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002331:Carnitine / Q000378:metabolism / Q000494:pharmacology*; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004195:Disease Models, Animal; D018450:Disease Progression; D004353:Drug Evaluation, Preclinical; D051275:Glucose Transporter Type 4; D006333:Heart Failure / Q000139:chemically induced / Q000150:complications*; D020287:In Situ Nick-End Labeling; D008111:Liver Function Tests; D008297:Male; D016686:Monocrotaline; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009124:Muscle Proteins; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020966:Muscular Disorders, Atrophic / Q000209:etiology / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D018995:Myosin Heavy Chains / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013107:Sphingolipids / Q000097:blood; D019311:Staurosporine; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D020033:Protein Isoforms; C495694:Slc2a4 protein, rat; D013107:Sphingolipids; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D016686:Monocrotaline; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9; D020169:Caspases; D018995:Myosin Heavy Chains; D019311:Staurosporine; D002331:Carnitine