Premium
A novel pathway of whereby sPLA2 stimulates ABCA1‐mediated phospholipid efflux via ERK and PPARalpha/RXR
Author(s) -
Agassandian Marianna,
Mallampalli Rama
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a94-b
Subject(s) - abca1 , efflux , mapk/erk pathway , chemistry , retinoid x receptor , microbiology and biotechnology , biology , biochemistry , signal transduction , transcription factor , transporter , gene , nuclear receptor
Secretory phospholipase A2‐IB (sPLA2‐IB) exerts diverse biological responses in cells. Herein, we demonstrate that exogenous sPLA2‐IB stimulates basolateral efflux of phosphatidylcholine (PC) in a murine lung epithelial (MLE) cell line. sPLA2‐IB stimulation of PC efflux was mediated, in part, by the ATP‐binding cassette transporter (ABCA1) as pretreatment of cells with the ABCA1 inhibitor, glyburide, selectively attenuated sPLA2‐induced PC export. To determine mechanisms whereby sPLA2‐IB regulates phospholipid export, we examined the heterodimeric receptors, retinoid X receptor (RXR) and the peroxisome proliferator‐activated receptor alpha (PPAR alpha) that participate in ABCA1 gene expression. Exogenous sPLA2‐IB increased PPAR alpha, RXR, and also activated p44/p42 kinase. Further, sPLA2‐stimulation of PC efflux via induction of PPAR alpha and p44/p42 kinase activation was blocked using MK886 or PD98059, respectively. Pull down assays demonstrated that sPLA2‐IB binds to its native mannose receptor in cells. Thus, these results suggest that the PPARalpha receptor heterodimerizes with RXR for stimulation of ABCA1 gene transcription in response to sPLA2. This study also lends support to the idea that sPLA2‐IB decreases cellular PC levels by stimulating ABCA1‐mediated phospholipid export via a receptor‐mediated mechanism activating p44/p42 kinase followed by PPARalpha/RXR heterodimerization in murine lung epithelia.