Modulation of apolipoprotein D expression and translocation under specific stress conditions.

Apolipoprotein D is a lipocalin, primarily associated with high density lipoproteins in human plasma. Its expression is induced in several pathological and stressful conditions including growth arrest suggesting that it could act as a nonspecific stress protein. A survey of cellular stresses shows those causing an extended growth arrest, as hydrogen peroxide and UV light increase apoD expression. Alternatively, lipopolysaccharide (LPS), a pro-inflammatory agonist showed a time- and dose-dependent effect on apoD expression that correlates with an increase in proliferation. At the promoter level, NF-kB, AP-1 and APRE-3 proved to be the elements implicated in the LPS response. Colocalization of apoDh-GFP fusion constructs with DNA and Golgi markers, immunocytochemistry of the endogenous protein and cell fractionation showed that both serum starvation and LPS treatment caused a displacement of apoD localization. In normal conditions, apoD is mainly perinuclear but it accumulates in cytoplasm and nucleus under these stress conditions. Since nuclear apoD appears derived from the secreted protein, it may act as an extracellular ligand transporter as well as a transcriptional regulator depending on its location. This role of apoD inside the cell is not only dependent of endogenous apoD but may also be provided by exogenous apoD entering the cell.