The rapid and reversible association of phosphofructokinase with myocardial membranes during myocardial ischemia.
Myocardial calcium-independent phospholipase A2 (PLA2) activity is mediated by a 400 kDa catalytic complex comprised of a tetramer of phosphofructokinase (PFK) and a 40 kDa catalytic subunit [1,2]. During myocardial ischemia, calcium-independent PLA2 activity rapidly and reversibly translocates from the cytosol to a membrane-associated compartment where it has been implicated as a mediator of ischemic damage [3,4]. Herein we demonstrate that the majority of both PFK mass and activity is translocated from the cytosol to a membrane-associated compartment prior to the onset of irreversible myocytic injury and that translocated PFK is catalytically inactive while membrane-associated. Furthermore, reperfusion of ischemic myocardium, or treatment of membranes derived from ischemic myocardium with ATP results in the conversion of both PFK mass and activity from its membrane-associated state to a soluble, catalytically-competent form. Collectively, these studies demonstrate that the concomitant changes in glycolysis and phospholipid hydrolysis during early myocardial ischemia result, at least in part, from the translocation of a common regulatory polypeptide critical in both processes.
Hazen
S L
SL
Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO.
Wolf
M J
MJ
Ford
D A
DA
Gross
R W
RW
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000494:pharmacology; D002462:Cell Membrane / Q000201:enzymology; D003600:Cytosol / Q000201:enzymology; D046911:Macromolecular Substances; D017202:Myocardial Ischemia / Q000201:enzymology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000201:enzymology*; D010732:Phosphofructokinase-1 / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D011817:Rabbits
D046911:Macromolecular Substances; D000255:Adenosine Triphosphate; D010732:Phosphofructokinase-1; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium