The rapid and reversible association of phosphofructokinase with myocardial membranes during myocardial ischemia

FEBS Letters

Hazen, Stanley L.¹  Gross, Richard W.¹  Ford, David A.¹  Wolf, Matthew J.¹ 

[1] Division of Bioorganic Chemistry and Molecular Pharmacology, Departments of Internal Medicine, Chemistry and Molecular Biology & Pharmacology, 660 South Euclid, Box 8020, Washington University School of Medicine, St. Louis, MO, USA

关键词: Phosphofructokinase;    Ischemia;    Phospholipase A2;    Myocardium;   

DOI  :  10.1016/0014-5793(94)80418-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown