Regulation of group VIA phospholipase A2 expression by sterol availability.

Journal Article (Journal Article)

Several lines of evidence suggest that glycerophospholipid mass is maintained through the coordinate regulation of CTP:phosphocholine cytidylyltransferase-alpha (CTalpha) and the group VIA calcium-independent phospholipase A2 (iPLA2). CTalpha expression is modulated by sterol and this is mediated in part through sterol regulatory element binding proteins (SREBP). In this report, we investigate the possibility that iPLA2 expression is controlled in a similar manner. When Chinese hamster ovary (CHO) cells were cultured under sterol-depleted conditions, iPLA2 catalytic activity, mRNA, and protein were induced by between two- and threefold. These inductions were suppressed when the cells were supplemented with exogenous sterols. Luciferase reporter assays indicated that sterol depletion induced transcription of iPLA2, an analysis of the 5' flanking region suggested that the iPLA2 gene contained a putative sterol regulatory element (SRE), and electrophoretic mobility shift assay (EMSA) analysis indicated that this element can bind SREBP-2. Notably, a mutant CHO cell line (SRD4) that constitutively generates mature SREBP proteins exhibited increased iPLA2 activity and expression compared to wild-type cells. These data suggest that iPLA2 expression is regulated in a manner consistent with other important genes in sterol and glycerophospholipid metabolism. Such coordinate regulation may be essential for maintaining the lipid composition of cell membranes.

Full Text

Duke Authors

Cited Authors

  • Seashols, SJ; del Castillo Olivares, A; Gil, G; Barbour, SE

Published Date

  • August 30, 2004

Published In

Volume / Issue

  • 1684 / 1-3

Start / End Page

  • 29 - 37

PubMed ID

  • 15450207

International Standard Serial Number (ISSN)

  • 0006-3002

Digital Object Identifier (DOI)

  • 10.1016/j.bbalip.2004.05.003

Language

  • eng

Conference Location

  • Netherlands