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Vol. 16, Issue 8, 3800-3809, August 2005

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Cytosolic Phospholipase A₂- Mediates Endothelial Cell Proliferation and Is Inactivated by Association with the Golgi Apparatus

School of Biochemistry and Microbiology, University of Leeds, Leeds LS2 9JT, United Kingdom

Submitted February 25, 2005; Revised April 27, 2005; Accepted May 24, 2005
Monitoring Editor: Vivek Malhotra

Arachidonic acid and its metabolites are implicated in regulating endothelial cell proliferation. Cytosolic phospholipase A₂- (cPLA₂) is responsible for receptor-mediated arachidonic acid evolution. We tested the hypothesis that cPLA₂ activity is linked to endothelial cell proliferation. The specific cPLA₂ inhibitor, pyrrolidine-1, inhibited umbilical vein endothelial cell (HUVEC) proliferation in a dose-dependent manner. Exogenous arachidonic acid addition reversed this inhibitory effect. Inhibition of sPLA₂ did not affect HUVEC proliferation. The levels of cPLA₂ did not differ between subconfluent and confluent cultures of cells. However, using fluorescence microscopy we observed a novel, confluence-dependent redistribution of cPLA₂ to the distal Golgi apparatus in HUVECs. Association of cPLA₂ with the Golgi was linked to the proliferative status of HUVECs. When associated with the Golgi apparatus, cPLA₂ activity was seen to be 87% inhibited. Relocation of cPLA₂ to the cytoplasm and nucleus, and cPLA₂ enzyme activity were required for cell cycle entry upon mechanical wounding of confluent monolayers. Thus, cPLA₂ activity and function in controlling endothelial cell proliferation is regulated by reversible association with the Golgi apparatus.

Abbreviations used: AA, arachidonic acid; BFA, brefeldin A; cPLA₂, cytosolic phospholipase A₂-; ERGIC-53, endoplasmic reticulum-Golgi intermediate compartment-53; GalT, -1,4-galactosyltransferase; HUVEC, human umbilical vein endothelial cell; iPLA₂, calcium-independent phospholipase A₂; ManII, mannosidase II; sPLA₂, secretory phospholipase A₂

Address correspondence to: J. H. Walker (j.h.walker{at}leeds.ac.uk).

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