Ischemic loss of sarcolemmal dystrophin and spectrin: Correlation with myocardial injury

被引:56
作者
Armstrong, SC
Latham, CA
Shivell, LC
Ganote, CE
机构
[1] E Tennessee State Univ, James H Quillen Coll Med, Dept Pathol, Johnson City, TN 37614 USA
[2] Vet Affairs Med Ctr, Johnson City, TN 37614 USA
关键词
ischemia; cytoskeleton; cardiomyocytes; sarcolemma; ischemic preconditioning;
D O I
10.1006/jmcc.2001.1380
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Sarcolemmal blebbing and rupture are prominent features of irreversible ischemic myocardial injury. Dystrophin and spectrin are sarcolemmal structural proteins. Dystrophin links the transmembrane dystroglycan complex and extracellular laminin receptors to intracellular F-actin. Spectrin forms the backbone of the membrane skeleton confering an elastic modulus to the sarcolemmal membrane, An ischemic loss of membrane dystrophin and spectrin, in ischemically pelleted rabbit cardiomyocytes or in vivo 30-45 min permanently ischemic, LAD-ligated hearts, was detected by immunofluorescence with monoclonal antibodies, Western blots of light and heavy microsomal vesicles and Triton-extracted membrane fractions from ischemic myocytes demonstrated a rapid loss of dystrophin coincident with sub-sarcolemmal bleb formation. subsequent to a hypotonic challenge. The loss of spectrin from purified sarcolemma of autolysed rabbit heart, and both isolated membrane vesicles and Triton solubilized membrane fractions of ischemic cardiomyocytes correlated linearly with the onset of osmotic fragility as assessed by membrane rupture, subsequent to a hypotonic challenge. In contrast to the ischemic loss of dystrophin and spectrin from the membrane, the dystrophin-associated proteins, alpha -sarcoglycan and beta -dystroglycan and the integral membrane protein, sodium-calcium exchanger, were maintained in the membrane fraction of ischemic cells as compared to oxygenated cells. Preconditioning protected cells, but did not significantly alter ischemic dystrophin or spectrin translocation. This previously unrecognized loss of sarcolemmal dystrophin and spectrin may be the molecular basis for sub-sarcolemmal bleb formation and membrane fragility during the transition from reversible to irreversible ischemic myocardial injury. (C) 2001 Academic Press.
引用
收藏
页码:1165 / 1179
页数:15
相关论文
共 66 条
  • [41] The association of cardiac dystrophin with myofibrils/Z-disc regions in cardiac muscle suggests a novel role in the contractile apparatus
    Meng, HP
    Leddy, JJ
    Frank, J
    Holland, P
    Tuana, BS
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (21) : 12364 - 12371
  • [42] DECREASED OSMOTIC STABILITY OF DYSTROPHIN-LESS MUSCLE-CELLS FROM THE MDX MOUSE
    MENKE, A
    JOCKUSCH, H
    [J]. NATURE, 1991, 349 (6304) : 69 - 71
  • [43] MILNER RE, 1993, J BIOL CHEM, V268, P21901
  • [44] Abnormal immunostaining for dystrophin in isoproterenol induced acute myocardial injury in rats: Evidence for change in dystrophin in the absence of genetic defect
    Miyazato, H
    Biro, S
    Setoguchi, M
    Maeda, M
    Tashiro, T
    Nakao, S
    Tanaka, H
    [J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1997, 29 (04) : 1217 - 1223
  • [45] Cellular ATP depletion induces disruption of the spectrin cytoskeletal network
    Molitoris, BA
    Dahl, R
    Hosford, M
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-RENAL FLUID AND ELECTROLYTE PHYSIOLOGY, 1996, 271 (04): : F790 - F798
  • [46] EFFECT OF THE LEVEL OF ATP AND OF THE STATE OF SPECTRIN ON OSMOTIC PROPERTIES OF BOVINE ERYTHROCYTES
    MOSIOR, M
    BOBROWSKA, M
    GOMULKIEWICZ, J
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1990, 1022 (03) : 355 - 360
  • [47] Ohlendieck K, 1996, EUR J CELL BIOL, V69, P1
  • [48] DYSTROPHIN-GLYCOPROTEIN COMPLEX IS HIGHLY ENRICHED IN ISOLATED SKELETAL-MUSCLE SARCOLEMMA
    OHLENDIECK, K
    ERVASTI, JM
    SNOOK, JB
    CAMPBELL, KP
    [J]. JOURNAL OF CELL BIOLOGY, 1991, 112 (01) : 135 - 148
  • [49] RAPID MICROASSAY FOR PROTEIN-KINASE-C TRANSLOCATION IN SWISS 3T3 CELLS
    PELECH, SL
    MEIER, KE
    KREBS, EG
    [J]. BIOCHEMISTRY, 1986, 25 (26) : 8348 - 8353
  • [50] DYSTROPHIN PREDOMINANTLY LOCALIZES TO THE TRANSVERSE TUBULE/Z-LINE REGIONS OF SINGLE VENTRICULAR MYOCYTES AND EXHIBITS DISTINCT ASSOCIATIONS WITH THE MEMBRANE
    PERI, V
    AJDUKOVIC, B
    HOLLAND, P
    TUANA, BS
    [J]. MOLECULAR AND CELLULAR BIOCHEMISTRY, 1994, 130 (01) : 57 - 65