title: Statin or fibrate chronic treatment modifies the proteomic profile of rat skeletal muscle.
abstract: Statins and fibrates can cause myopathy. To further understand the causes of the damage we performed a proteome analysis in fast-twitch skeletal muscle of rats chronically treated with different hypolipidemic drugs. The proteomic maps were obtained from extensor digitorum longus (EDL) muscles of rats treated for 2-months with 10mg/kg atorvastatin, 20 mg/kg fluvastatin, 60 mg/kg fenofibrate and control rats. The proteins differentially expressed were identified by mass spectrometry and further analyzed by immunoblot analysis. We found a significant modification in 40 out of 417 total spots analyzed in atorvastatin treated rats, 15 out of 436 total spots in fluvastatin treated rats and 21 out of 439 total spots in fenofibrate treated rats in comparison to controls. All treatments induced a general tendency to a down-regulation of protein expression; in particular, atorvastatin affected the protein pattern more extensively with respect to the other treatments. Energy production systems, both oxidative and glycolytic enzymes and creatine kinase, were down-regulated following atorvastatin administration, whereas fenofibrate determined mostly alterations in glycolytic enzymes and creatine kinase, oxidative enzymes being relatively spared. Additionally, all treatments resulted in some modifications of proteins involved in cellular defenses against oxidative stress, such as heat shock proteins, and of myofibrillar proteins. These results were confirmed by immunoblot analysis. In conclusions, the proteomic analysis showed that either statin or fibrate administration can modify the expression of proteins essential for skeletal muscle function suggesting potential mechanisms for statin myopathy.
authors.affiliation: Department of Pharmacobiology, Section of Pharmacology, Faculty of Pharmacy, University of Bari "Aldo Moro", Via Orabona 4, 70124 Bari, Italy.
authors.forename: Giulia Maria
authors.initials: GM
authors.lastname: Camerino
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Pellegrino
authors.forename: Lorenza
authors.initials: L
authors.lastname: Brocca
authors.forename: Claudio
authors.initials: C
authors.lastname: Digennaro
authors.forename: Diana Conte
authors.initials: DC
authors.lastname: Camerino
authors.forename: Sabata
authors.initials: S
authors.lastname: Pierno
authors.forename: Roberto
authors.initials: R
authors.lastname: Bottinelli
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015180:Electrophoresis, Gel, Two-Dimensional; D058607:Fibric Acids / Q000008:administration & dosage / Q000009:adverse effects*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015151:Immunoblotting; D007525:Isoelectric Focusing; D008297:Male; D018656:Muscle Fibers, Fast-Twitch / Q000187:drug effects / Q000378:metabolism; D009124:Muscle Proteins / Q000096:biosynthesis*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D009135:Muscular Diseases / Q000139:chemically induced / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D020543:Proteome / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D009124:Muscle Proteins; D020543:Proteome