Nuclear Translocation of Cytosolic Phospholipase A₂ is Induced by ATP Depletion

Phospholipase A₂ (PLA₂) enzymes may play a role in cellular injury due to ATP depletion. Renal Madin-Darby canine kidney cells were subjected to ATP depletion to assess the effects of cellular energy metabolism on cytosolic PLA₂ (cPLA₂) regulation. ATP depletion results in a decrease in soluble cPLA₂ activity and an increase in membrane-associated activity, which is reversed upon restoration of ATP levels by addition of dextrose. In ATP-depleted cells cPLA₂ mass shifts from cytosol to nuclear fractions. GFP-cPLA₂ is localized at the nuclear membrane of stably transfected ATP-depleted LLC-PK₁ cells under conditions where [Ca²⁺]_i is known to increase. cPLA₂ translocation does not occur if the increase in [Ca ²⁺]_i increase is inhibited. If [Ca²⁺] _i is allowed to increase when ATP is depleted and the cells are then lysed, cPLA₂ remains associated with nuclear fractions even if the homogenate [Ca²⁺] is markedly reduced. In contrast, cPLA ₂, which becomes associated with the nucleus when [Ca ²⁺]_i is increased using ionophore, readily dissociates from the nuclear fractions of ATP-replete cells upon reduction of homogenate [Ca²⁺]. Okadaic acid inhibits the ATP depletion-induced association of cPLA₂ with nuclear fractions. Thus energy deprivation results in [Ca²⁺]-induced nuclear translocation, which is partially prevented by a phosphatase inhibitor.