Distinct roles of two intracellular phospholipase A2s in fatty acid release in the cell death pathway. Proteolytic fragment of type IVA cytosolic phospholipase A2alpha inhibits stimulus-induced arachidonate release, whereas that of type VI Ca2+-independent phospholipase A2 augments spontaneous fatty acid release

J Biol Chem. 2000 Jun 16;275(24):18248-58. doi: 10.1074/jbc.M000271200.


Cytosolic phospholipase A(2)alpha (cPLA(2)alpha; type IVA), an essential initiator of stimulus-dependent arachidonic acid (AA) metabolism, underwent caspase-mediated cleavage at Asp(522) during apoptosis. Although the resultant catalytically inactive N-terminal fragment, cPLA(2)(1-522), was inessential for cell growth and the apoptotic process, it was constitutively associated with cellular membranes and attenuated both the A23187-elicited immediate and the interleukin-1-dependent delayed phases of AA release by several phospholipase A(2)s (PLA(2)s) involved in eicosanoid generation, without affecting spontaneous AA release by PLA(2)s implicated in phospholipid remodeling. Confocal microscopic analysis revealed that cPLA(2)(1-522) was distributed in the nucleus. Pharmacological and transfection studies revealed that Ca(2+)-independent PLA(2) (iPLA(2); type VI), a phospholipid remodeling PLA(2), contributes to the cell death-associated increase in fatty acid release. iPLA(2) was cleaved at Asp(183) by caspase-3 to a truncated enzyme lacking most of the first ankyrin repeat, and this cleavage resulted in increased iPLA(2) functions. iPLA(2) had a significant influence on cell growth or death, according to cell type. Collectively, the caspase-truncated form of cPLA(2)alpha behaves like a naturally occurring dominant-negative molecule for stimulus-induced AA release, rendering apoptotic cells no longer able to produce lipid mediators, whereas the caspase-truncated form of iPLA(2) accelerates phospholipid turnover that may lead to apoptotic membranous changes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Arachidonic Acid / metabolism*
  • Calcimycin / pharmacology
  • Calcium / metabolism*
  • Caspases / metabolism
  • Cytosol / enzymology
  • Fatty Acids / metabolism*
  • Group IV Phospholipases A2
  • Group VI Phospholipases A2
  • Humans
  • Ionophores / pharmacology
  • Isoenzymes / physiology*
  • Phospholipases A / physiology*
  • Phospholipases A2
  • Signal Transduction
  • Transfection
  • U937 Cells


  • Fatty Acids
  • Ionophores
  • Isoenzymes
  • Arachidonic Acid
  • Calcimycin
  • Phospholipases A
  • Group IV Phospholipases A2
  • Group VI Phospholipases A2
  • PLA2G6 protein, human
  • Phospholipases A2
  • Caspases
  • Calcium