Mechanism of Statin-Induced Contractile Dysfunction in Rat Cultured Skeletal Myofibers
スポンサーリンク
概要
- 論文の詳細を見る
An adverse effect of statins, cholesterol-lowering drugs, is contractile dysfunction of skeletal muscles. We investigated the mechanism underlying this effect in cultured myofibers isolated from rats. Fluvastatin (Flv) for 72 h decreased caffeine- and ionomycin-induced contraction of myofibers and Ca2+ release from sarcoplasmic reticulum (SR). Ca2+-shortening curves measured in skinned myofibers indicated that myofibrillar Ca2+ sensitivity was unaffected by Flv. A luciferin–luciferase assay revealed less ATP contents in Flv-treated myofibers. Among mevalonate metabolites, including geranylgeranylpyrophosphate (GGPP), farnesylpyrophosphate (FPP), coenzyme Q9, and coenzyme Q10, only GGPP prevented Flv-induced ATP reduction. A selective Rab geranylgeranyltransferase (GG transferase) inhibitor, perillyl alcohol (POH), and a specific GG transferase-I inhibitor, GGTI-298, both mimicked Flv in decreasing ATP and contraction. Mitochondrial membrane potential was decreased by Flv, and this effect was rescued by GGPP and mimicked by POH and GGTI-298. An endoplasmic reticulum (ER)-to-Golgi traffic inhibitor, brefeldin A, and a Rho inhibitor, membrane permeable exoenzyme C3 transferase, both decreased ATP. We conclude that statin-induced contractile dysfunction is due to reduced Ca2+ release from SR and reduced ATP levels in myofibers with damaged mitochondria. GGPP depletion and subsequent inactivation of Rab1, possibly along with Rho, may underlie the mitochondrial damage by Flv.
著者
-
Kimura Junko
Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University
-
WAGURI Satoshi
Department of Anatomy and Histology, Fukushima Medical University, School of Medicine
-
Yamamoto Masaya
Department of Cardiology, Toho university Ohashi medical center
-
Tanaka Syoko
Department of Pharmacology, School of Medicine, Fukushima Medical University, Japan
-
Sakamoto Kazuho
Department of Pharmacology, School of Medicine, Fukushima Medical University, Japan
-
Mizuno Anna
Department of Pharmacology, School of Medicine, Fukushima Medical University, Japan
-
Ono Tomoyuki
Department of Pharmacology, School of Medicine, Fukushima Medical University, Japan
-
Waguri Satoshi
Department Of Anatomy And Histology Fukushima Medical University
-
Yamamoto Masaya
Department Of Applied Chemistry And Chemical Engineering Yamaguchi University
-
Ono Tomoyuki
Department Of Pharmacology Fukushima Medical College
-
Sakamoto Kazuho
Department Of Molecular And Cellular Pharmacology Graduate School Of Pharmaceutical Sciences Nagoya
-
Sakamoto Kazuho
Department Of Pharmacology School Of Medicine Fukushima Medical University
-
Yamamoto Masaya
Department Of Anatomy And Histology School Of Medicine Fukushima Medical University
-
Mizuno Anna
Department Of Pharmacology School Of Medicine Fukushima Medical University
-
Tanaka Syoko
Department Of Pharmacology School Of Medicine Fukushima Medical University
関連論文
- Development of a Quinazoline-Based Chelating Ligand for Zinc Ion and Its Application to Validation of a Zinc-Ion-Coordinated Compound
- Specific depletion of GGA2 causes cathepsin D missorting in HeLa cells
- IIA-30 Autophagy in cathepsin D-deficient mice expressing GFP-LC3(THE 46TH ANNUAL MEETING OF THE JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY)
- II-C-04 Expression of cathepsin C in normal and injured mouse brains(THE 45TH ANNUAL MEETING OF THE JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY)
- II-C-07 Early-phase redistribution of the cation-independent mannose 6-phosphate receptor by U18666A treatment in HeLa cells
- P-45-B Cathepsin D Deficiency Induces Autophagy in Neurons of Mouse Brain(THE JOINT MEETING OF THE 44TH ANNUAL MEETING OF THE JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY AND THE 35TH ANNUAL MEETING OF THE CLINICAL ELECTRON MICROSCOPY SOCIETY OF JAPA
- P-38-A Predominant expression of the short form of GGA3 in human cell lines and tissues(THE JOINT MEETING OF THE 44TH ANNUAL MEETING OF THE JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY AND THE 35TH ANNUAL MEETING OF THE CLINICAL ELECTRON MICROSCOPY S
- The Expression of Tripeptidyl Peptidase I in Various Tissues of Rats and Mice
- Immunocytochemical Localization of Chromogranin A and Secretogranin II in Female Rat Gonadotropes
- Immunocytochemical Localization of Angiotensinogen in Rat Hepatocytes
- The Fate of Effete Epithelial Cells at the Villus Tips of the Human Small Intestine
- Controlled Release of Matrix Metalloproteinase-1 Plasmid DNA Prevents Left Ventricular Remodeling in Chronic Myocardial Infarction of Rats
- PE-077 Blocking Effect of SN-6, a Novel Benzyloxyphenyl Derivative, on Na^+/Ca^ Exchange Current in Single Guinea-pig Cardiac Ventricular Myocytes(Cardiovascular pharmacology, basic/clinical-3 (H) PE13,Poster Session (English),The 70th Anniversary Ann
- PJ-469 Predictive Factors of a Favorable Responder after Renal Artery Stenting in Patients with Renal Artery Stenosis(PJ079,Peripheral Circulation/Vascular Disease (Therapy) 2 (H),Poster Session (Japanese),The 73rd Annual Scientific Meeting of The Japanes
- OE-262 Outcomes of endovascular treatment for TASC A to D iliac artery lesions(Peripheral circulation/Vascular disease(01)(H),Oral Presentation(English),The 72nd Annual Scientific Meeting of the Japanese Circulation Society)
- Purification, cDNA cloning, and secretory properties of FLRG protein from PC12 cells and the distribution of FLRG mRNA and protein in rat tissues
- Mechanism of Statin-Induced Contractile Dysfunction in Rat Cultured Skeletal Myofibers
- Fabrication of three-dimensional cell scaffolds with spatial gradients of biomolecules
- 2P012 ショウジョウバエ由来GGAの溶液構造解析(蛋白質-構造,第48回日本生物物理学会年会)
- Recovery of Learning and Memory by Gene Therapy Using Hepatocyte Growth Factor Gene After Focal Cerebral Ishcemia in Rats(Gene Therapy/Genetic Engineering (IHD), The 69th Annual Scientific Meeting of the Japanese Circulation Society)
- Enhanced Osteoinduction by Biodegradable Gelatin-β-tricalcium Phosphate Sponge Capable for Bone Morphogenetic Protein Release(International Symposium of Maxillofacial and Oral Regenerative Biology in Okayama 2005)
- Enhanced osteoinduction by biodegradable gelatin-tricalcium phosphate sponge incorporating bone morphogenetic protein(13^ Annual Meeting of the Society for Hard Tissue Regenerative Biology)
- A Novel Approach to Therapeutic Angiogenesis for Patients With Critical Limb Ischemia by Sustained Release of Basic Fibroblast Growth Factor Using Biodegradable Gelatin Hydrogel : An Initial Report of the Phase I-IIa Study
- 4 Control-release of MMP-1 Plasmid DNA Improved Contractility and Altered Na/Ca Exchange of Cardiomyocytes Isolated from Rat Chronic Myocardial Infarction Heart(The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- 4 Towards New Era for Regenerative Medicine in Cardiovascular Area(Regeneration Therapy Using Tissue Engineering, The 71st Annual Scientific Meeting of the Japanese Circulation Society)
- Microsomal Aldehyde Oxygenase (MALDO) for Tolualdehydes, Active Metabolites of Xylenes, in the Mouse Liver and Lung
- Properties of osteoinduction and BMP-2 release in functionally graded HAp(15thAnnual Meeting of the Society for Hard Tissue Regenerative Biology,Session 2)
- Inhibitory Action of Troglitazone, an Insulin-Sensitizing Agent, on the Calcium Current in Cardiac Ventricular Cells of Guinea Pig
- MUC-1 mucin expression in invasive areas of intraductal papillary mucinous tumors of the pancreas
- Increased high frequency components of QRS complex detected by wavelet analysis predicts vulnerability to ventricular tachycardia in hypertensive rats
- Comprehensive Analyses of Arrhythmogenic Substrates and Vulnerability to Ventricular Tachycardia in Left Ventricular Hypertrophy in Salt-Sensitive Hypertensive Rats
- Pharmacological Significance of the Blocking Action of the Intravenous General Anesthetic Propofol on the Slow Component of Cardiac Delayed Rectifier K^+ Current
- Anomalous Susceptibility of UPd_2Al_3 near the Upper Critical Field
- Removal of Acetaldehyde and Propionaldehyde from Waste Gas in Packed Column with Immobilized Activated Sludge Gel Beads
- The female partner's satisfaction with sildenafil citrate treatment of erectile dysfunction
- Inhibitory Effects of Isoliquiritigenin and Licorice Extract on Voltage-Dependent K^+ Currents in H9c2 Cells
- Aggressive Statin Therapy in Multicenter Trial and Effectiveness for the Reduction of Intra-myocardial Damage Caused by non-Q-wave Acute Coronary Syndrome(Acute Coronary Syndrome, Basic/Clinical 1 (IHD), The 69th Annual Scientific Meeting of the Japanese
- Topics on the Na^+/Ca^ Exchanger : Pharmacological Characterization of Na^+/Ca^ Exchanger Inhibitors
- Effects of Anions on ATP-Induced[Ca^]_i Increase in NG108-15 Cells
- Inhibitory Effects of Metals on ATP-Induced Current Through P2X_7 Receptor in NG108-15 Cells
- Characteristics of ATP-Induced Current Through P2X_7 Receptor in NG108-15 Cells : Unique Antagonist Sensitivity and Lack of Pore Formation
- Blocking Effect of Bepridil on Na^+/Ca^ Exchange Current in Guinea Pig Cardiac Ventricular Myocytes
- Lysophosphatidylcholine Increases Na^+/Ca^ Exchanger Expression via RhoB-Geranylgeranylation in H9c2 Cells
- Na^+-Ca^ Exchanger Expression and Its Modulation(Functional Changes Induced by Long-Term Stimulation of Nicotinic Acetylcholine Receptors)
- Inhibitory Effect of Thiopental on Ultra-rapid Delayed Rectifier K^+ Current in H9c2 Cells
- Effects of a Novel Cardioprotective Drug, JTV-519, on Membrane Currents of Guinea Pig Ventricular Myocytes
- Effects of YT : 146 [2 : (1 : Octyny1) Adenosine], an Adenosine A_ Receptor Agonist, on cAMP Production and Noradrenaline Release in PC12 Cells
- Correlation Between Adenine Nucleotide-Induced Cyclic AMP Elevation and Extracellular Adenosine Formation in NG108-15 Cells
- Regeneration induction therapy based on DDS technology of growth factors(15thAnnual Meeting of the Society for Hard Tissue Regenerative Biology,Session 2)
- A Novel Monoclonal Antibody Specific for Sialylated MUC1 Mucin
- Selective Up-regulation of P2X_4-Receptor Gene Expression by Interferon-γ in Vascular Endothelial Cells
- Acidic Preconditioning Inhibits Na^+/H^+ and Na^+/Ca^ Exchanger Interaction via PKCε in Guinea-Pig Ventricular Myocytes
- Mechanism of Na^+/Ca^ Exchanger Activation by Hydrogen Peroxide in Guinea-Pig Ventricular Myocytes
- Chronic Administration of Amiodarone Does Not Affect Na^+/Ca^ Exchange Current in Guinea Pig Cardiac Ventricular Myocytes
- A Novel Opener of Large-Conductance Ca^-Activated K^+ (BK) Channel Reduces Ischemic Injury in Rat Cardiac Myocytes by Activating Mitochondrial K_ Channel
- PJ-543 Hydrogen Peroxide Activates Na+/Ca2+ Exchanger through Two Different Signaling Pathways in Guinea-Pig Ventricular Myocytes(Myocardial Ischemia-Reperfusion, Basic and Clinical 3 (M) : PJ91)(Poster Session (Japanese))
- Mechanisms Underlying the Activation of Large Conductance CA^-Activated K^+ Channels by Nordihydroguaiaretic Acid
- Inhibitory Effect of Azimilide on Na+/Ca2+ Exchange Current in Guinea-Pig Cardiac Myocytes
- MANNOSE 6-PHOSPHATE RECEPTOR TRAFFICKING IN LIVING CELLS(THE SIXTH JAPAN-CHINA JOINT SEMINAR ON HISTOCHEMISTRY AND CYTOCHEMISTRY)
- Report on the Women in Physiology Symposium in IUPS 2009
- Mechanism of Pulmonary Cytochrome P450 Inactivation by Tolualdehydes, Active Metabolites of Xylenes (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
- Metabolic Reaction of Tolualdehydes by Microsomal Aldehyde Oxygenase (MALDO) in Lung (Proceedings of the 19th Symposium on Toxicology and Environmental Health)
- Arabidopsis thaliana Has a Set of J Proteins in the Endoplasmic Reticulum that are Conserved from Yeast to Animals and Plants
- Inactivation of Membrane Surface Ecto-5′-nucleotidase by Sodium Nitroprusside in C6 Glioma Cells
- Muscarinic M2 receptors inhibit Ca^-activated K^+channel in rat bladder smooth muscle
- Forefront of Na^+/Ca^ Exchanger Studies : Stoichiometry of Cardiac Na^+/Ca^ Exchanger ; 3:1 or 4:1?
- Topics on the Na^+/Ca^ Exchanger : Preface
- Inactivation of Membrane Surface Ecto-5'-nucleotidase by Sodium Nitroprusside in C6 Glioma Cells
- Mechanism of Statin-Induced Contractile Dysfunction in Rat Cultured Skeletal Myofibers
- Inhibitory Effect of Azimilide on Na+^/Ca^ Exchange Current in Guinea-Pig Cardiac Myocytes
- Forefront of Na+/Ca2+ Exchanger Studies: Stoichiometry of Cardiac Na+/Ca2+ Exchanger; 3:1 or 4:1?
- Inhibitory Effects of Citrus Polymethoxyflavones, Nobiletin and its Analogues, on Acetylcholinesterase Activity
- Hypoxic Stress Induces Transient Receptor Potential Melastatin 2 (TRPM2) Channel Expression in Adult Rat Cardiac Fibroblasts
- Inhibitory Effect of Cibenzoline on Na^+/Ca^ Exchange Current in Guinea-Pig Cardiac Ventricular Myocytes
- Inhibitory effect of β-hydroxybutyric acid on L-type Ca^{2+} current under β-adrenergic stimulation in guinea pig Cardiac ventricular myocytes
- Simple and High-Performance Signal Reception Method for the Readout of an Imaging Plate
- EFFECT OF ORAL L-ARGININE ADMINISTRATION ON EXHALED NITRIC OXIDE (NO) CONCENTRATION IN HEALTHY VOLUNTEERS
- Characterization of the activity of a platelet activating factor antagonist, CV-3988.
- QUALITATIVELY DIFFERENT RESPONSE OF ISOLATED RABBIT AORTA TO METHYLENE BLUE ADMINISTERED FROM INTIMAL AND ADVENTITIAL SURFACE
- Mechanism of Statin-Induced Rhabdomyolysis
- A COMPARATIVE STUDY ON CONTRACTILE RESPONSES OF RABBIT AND GUINEA PIG VASA DEFERENTIA TO ELECTRICAL FIELD STIMULATION
- THE INHIBITORY EFFECT OF SHAKUYAKUKANZOTO ON K+ CURRENT IN H9c2 CELLS
- Contribution of prostaglandin E2 to bradykinin-induced contraction in rabbit urinary detrusor.
- Upregulation of N-methyl-D-aspartate receptor subunits and c-Fos expressing genes in PC12D cells by nobiletin
- Stromal-derived factor-1 delivered via hydrogel drug-delivery vehicle accelerates wound healing in vivo