MODIFICATION OF SUBCELLULAR ORGANELLES IN PRESSURE-OVERLOADED HEART BY ETOMOXIR, A CARNITINE PALMITOYLTRANSFERASE-I INHIBITOR

被引:69
作者
RUPP, H
ELIMBAN, V
DHALLA, NS
机构
[1] ST BONIFACE GEN HOSP, DIV CARDIOVASC SCI, 351 TACHE AVE, WINNIPEG R2H 2A6, MANITOBA, CANADA
[2] UNIV MANITOBA, FAC MED, DEPT PHYSIOL, WINNIPEG R2H 2A6, MANITOBA, CANADA
关键词
HEART HYPERTROPHY; MYOSIN ISOZYMES; SARCOPLASMIC RETICULUM; CA2+-STIMULATED ATPASE; ETOMOXIR;
D O I
10.1096/fasebj.6.6.1531968
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To examine the signals regulating cardiac growth and molecular structure of subcellular organelles, cardiac hypertrophy was induced in rats by constriction of the abdominal aorta for 12-13 wk or by treatment with a carnitine palmitoyltransferase I inhibitor, etomoxir (12-15 mg/kg body wt) for 12-13 wk. In contrast to pressure overload, etomoxir redistributed the myosin isozyme population from V3 to V1 and increased the sarcoplasmic reticulum (SR) Ca2+-stimulated ATPase activity. When rats with pressure-overloaded hearts were treated with etomoxir, the cardiac hypertrophy was increased whereas the shift in myosin isozymes from V1 to V3 was prevented and the depression in SR Ca2+-stimulated ATPase activity was reversed. Plasma thyroid hormone and insulin concentrations were not altered but triglyceride concentrations were reduced in etomoxir-treated rats with pressure overload. The data demonstrate a dissociation between cardiac muscle growth and changes in subcellular organelles and indicate that a shift in myocardial substrate utilization may represent an important signal for molecular remodeling of the heart.
引用
收藏
页码:2349 / 2353
页数:5
相关论文
共 41 条
[1]   REGULATION OF FLUX THROUGH PYRUVATE-DEHYDROGENASE AND PYRUVATE-CARBOXYLASE IN RAT HEPATOCYTES - EFFECTS OF FATTY-ACIDS AND GLUCAGON [J].
AGIUS, L ;
ALBERTI, KGMM .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1985, 152 (03) :699-707
[2]  
Alder H, 1972, INTRO PROBABILITY ST
[3]   ROLE OF CHANGES IN MICROSOMAL CALCIUM-UPTAKE IN THE EFFECTS OF REPERFUSION OF CA-2+-DEPRIVED RAT HEARTS [J].
ALTO, LE ;
DHALLA, NS .
CIRCULATION RESEARCH, 1981, 48 (01) :17-24
[4]   CHRONIC INHIBITION OF FATTY-ACID OXIDATION - NEW MODEL OF DIASTOLIC DYSFUNCTION [J].
BRESSLER, R ;
GAY, R ;
COPELAND, JG ;
BAHL, JJ ;
BEDOTTO, J ;
GOLDMAN, S .
LIFE SCIENCES, 1989, 44 (25) :1897-1906
[5]   EFFECTS OF CHRONIC DOBUTAMINE ADMINISTRATION ON HEARTS OF NORMAL AND HYPERTENSIVE RATS [J].
BUTTRICK, P ;
MALHOTRA, A ;
FACTOR, S ;
GEENEN, D ;
SCHEUER, J .
CIRCULATION RESEARCH, 1988, 63 (01) :173-181
[6]   CALCIUM MOVEMENTS IN RELATION TO HEART FUNCTION [J].
DHALLA, NS ;
PIERCE, GN ;
PANAGIA, V ;
SINGAL, PK ;
BEAMISH, RE .
BASIC RESEARCH IN CARDIOLOGY, 1982, 77 (02) :117-139
[7]   SUBCELLULAR BASIS OF CARDIAC CONTRACTILE FAILURE [J].
DHALLA, NS ;
DAS, PK ;
SHARMA, GP .
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY, 1978, 10 (04) :363-385
[8]   SARCOPLASMIC RETICULAR CA-2+-PUMP ADAPTATION IN CARDIAC-HYPERTROPHY DUE TO PRESSURE OVERLOAD IN PIGS [J].
DHALLA, NS ;
ALTO, LE ;
HEYLIGER, CE ;
PIERCE, GN ;
PANAGIA, V ;
SINGAL, PK .
EUROPEAN HEART JOURNAL, 1984, 5 :323-328
[9]  
Dillmann W H, 1986, Adv Exp Med Biol, V194, P469
[10]  
EISTETTER K, 1986, Drugs of the Future, V11, P1034