PMID- 10400912
OWN - NLM
STAT- MEDLINE
DCOM- 19990730
LR  - 20190706
IS  - 1524-4571 (Electronic)
IS  - 0009-7330 (Linking)
VI  - 85
IP  - 1
DP  - 1999 Jul 9
TI  - Subcellular creatine kinase alterations. Implications in heart failure.
PG  - 68-76
AB  - We have tested the hypothesis that decreased functioning of creatine kinase (CK) 
      at sites of energy production and utilization may contribute to alterations in 
      energy fluxes and calcium homeostasis in congestive heart failure (CHF). Heart 
      failure was induced by aortic banding in 3-week-old rats. Myofilaments, 
      sarcoplasmic reticulum (SR), mitochondrial functions, and CK compartmentation 
      were studied in situ using selective membrane permeabilization of left 
      ventricular fibers with detergents (saponin for mitochondria and SR and Triton 
      X-100 for myofibrils). Seven months after surgery, animals were in CHF. A 
      decrease in total CK activity could be accounted for by a 4-fold decrease in 
      activity and content (Western blots) of mitochondrial CK and a 30% decrease in M 
      isoform of CK (MM-CK) activity. In myofibrils, maximal force, crossbridge 
      kinetics, and alpha-myosin heavy-chain expression decreased, whereas calcium 
      sensitivity of tension development remained unaltered. Myofibrillar CK efficacy 
      was unchanged. Calcium uptake capacities of SR were estimated from the surface of 
      caffeine-induced tension transient (SCa) after loading with different substrates. 
      In CHF, SCa decreased by 23%, and phosphocreatine was 2 times less efficient in 
      enhancing calcium uptake. Oxidative capacities of the failing myocardium measured 
      as oxygen consumption per gram of fiber dry weight decreased by 28%. Moreover, 
      the control of respiration by creatine, ADP, and AMP was severely impaired. Our 
      observations provide evidence that alterations in CK compartmentation may 
      contribute to alterations of energy fluxes and calcium homeostasis in CHF.
FAU - De Sousa, E
AU  - De Sousa E
AD  - Cardiologie Cellulaire et Moleculaire, U-446 INSERM, Faculte de Pharmacie, 
      Universite Paris-Sud, Chatenay-Malabry, France.
FAU - Veksler, V
AU  - Veksler V
FAU - Minajeva, A
AU  - Minajeva A
FAU - Kaasik, A
AU  - Kaasik A
FAU - Mateo, P
AU  - Mateo P
FAU - Mayoux, E
AU  - Mayoux E
FAU - Hoerter, J
AU  - Hoerter J
FAU - Bigard, X
AU  - Bigard X
FAU - Serrurier, B
AU  - Serrurier B
FAU - Ventura-Clapier, R
AU  - Ventura-Clapier R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Circ Res
JT  - Circulation research
JID - 0047103
RN  - EC 2.7.3.2 (Creatine Kinase)
SB  - IM
MH  - Animals
MH  - Creatine Kinase/*metabolism
MH  - Heart/physiopathology
MH  - Heart Failure/*enzymology/physiopathology
MH  - Male
MH  - Mitochondria, Heart/physiology
MH  - Myocardium/*enzymology
MH  - Myofibrils/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Sarcoplasmic Reticulum/physiology
MH  - Subcellular Fractions/*enzymology
MH  - Ventricular Function, Left/physiology
EDAT- 1999/07/13 00:00
MHDA- 1999/07/13 00:01
CRDT- 1999/07/13 00:00
PHST- 1999/07/13 00:00 [pubmed]
PHST- 1999/07/13 00:01 [medline]
PHST- 1999/07/13 00:00 [entrez]
AID - 10.1161/01.res.85.1.68 [doi]
PST - ppublish
SO  - Circ Res. 1999 Jul 9;85(1):68-76. doi: 10.1161/01.res.85.1.68.