Nuclear Translocation of Cytosolic Phospholipase A2 is Induced by ATP Depletion

Alice M. Sheridan, Adam Sapirstein, Nicole Lemieux, Brennan D. Martin, Dae Kyong Kim, Joseph V. Bonventre

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)29899-29905
Number of pages7
JournalJournal of Biological Chemistry
Volume276
Issue number32
DOIs
StatePublished - Aug 10 2001
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Sheridan, A. M., Sapirstein, A., Lemieux, N., Martin, B. D., Kim, D. K., & Bonventre, J. V. (2001). Nuclear Translocation of Cytosolic Phospholipase A2 is Induced by ATP Depletion. Journal of Biological Chemistry, 276(32), 29899-29905. https://doi.org/10.1074/jbc.M103758200