Membrane Ca2+Mg2+ -ATPase activation by calciumactivated neutral protease (CANP) in conditions where there is elevated intracellular Ca2+: An insight from erythrocytes of Duchenne muscular dystrophy (DMD)

Abstract

CANP along with cytosolic calcium has been found to be elevated in erythrocytes from DMD patients. An enhanced association of this enzyme to the erythrocyte membrane is also observed in this disease condition. Ca2+ Mg2+ -ATPase of DMD erythrocytes was also significantly elevated, indicative of the effort of the cells to pump out excess calcium. In normal erythrocytes incubated with calcium in the presence ofIonophore A 23187 there is a concomitant increase ofthe membrane-associated CANP and Ca2+ Mg2 + -ATPase activity, with time. A model has been proposed to suggest that in conditions where there is an increase in intracellular calcium the membrane-bound active CANP increases the pumping effiCIency of Ca H Mg2+ -A TPase by limited proteolysis. This model has been supported by in vitro activation of Ca2 + Mg2+ -ATPase by a homogeneous preparation of CANP.