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.
MeSH terms
-
Angiotensin II / blood
-
Animals
-
Apoptosis / drug effects*
-
Carnitine / metabolism
-
Carnitine / pharmacology*
-
Caspase 3
-
Caspase 9
-
Caspases / metabolism
-
Cell Nucleus / drug effects
-
Cell Nucleus / pathology
-
Cells, Cultured
-
Cytoprotection / drug effects
-
Disease Models, Animal
-
Disease Progression
-
Drug Evaluation, Preclinical
-
Glucose Transporter Type 4
-
Heart Failure / chemically induced
-
Heart Failure / complications*
-
In Situ Nick-End Labeling
-
Liver Function Tests
-
Male
-
Monocrotaline
-
Monosaccharide Transport Proteins / metabolism
-
Muscle Proteins*
-
Muscle, Skeletal / drug effects*
-
Muscle, Skeletal / pathology
-
Muscle, Skeletal / physiopathology
-
Muscular Disorders, Atrophic / etiology
-
Muscular Disorders, Atrophic / pathology
-
Muscular Disorders, Atrophic / physiopathology
-
Muscular Disorders, Atrophic / prevention & control*
-
Myosin Heavy Chains / metabolism
-
Protein Isoforms / metabolism
-
Rats
-
Rats, Sprague-Dawley
-
Sphingolipids / blood
-
Staurosporine
-
Tumor Necrosis Factor-alpha / analysis
Substances
-
Glucose Transporter Type 4
-
Monosaccharide Transport Proteins
-
Muscle Proteins
-
Protein Isoforms
-
Slc2a4 protein, rat
-
Sphingolipids
-
Tumor Necrosis Factor-alpha
-
Angiotensin II
-
Monocrotaline
-
Casp3 protein, rat
-
Casp9 protein, rat
-
Caspase 3
-
Caspase 9
-
Caspases
-
Myosin Heavy Chains
-
Staurosporine
-
Carnitine