Regulation by estrogen of synthesis and secretion of apolipoprotein A-I in the chicken hepatoma cell line, LMH-2A

The synthesis and secretion of apolipoprotein A-I (apoA-I) in response to the treatment with estrogen were investigated in the chicken hepatoma cell line, LMH-2A. Exposure of these cells to exogenous estrogen for up to 48 h results in a decrease of apoA-I production, as evident from Western blotting, immunoprecipitation, and immunofluorescence experiments. Likewise, the secretion of apoA-I is also decreased in estrogen-treated cells when compared to controls. However, under both conditions, the disappearance of the apoprotein from the cells occurs very rapidly and with similar kinetics. The bulk of apoA-I secreted from LMH-2A cells is recovered on lipoprotein particles with a buoyant density of greater than or equal to 1.10 g/ml, corresponding to HDL and heavy LDL. Interestingly, apoA-I is detectable on apoB-containing lipoproteins by sequential immunoprecipitation, suggesting that the two apoproteins co-reside at least on a subfraction of the secreted particles, or that apoB- and apoA-I-containing particles interact. These interactions are more pronounced in estrogen-treated cells, most likely due to the dramatic estrogen-mediated induction of apoB synthesis and secretion. (C) 2003 Elsevier Science B.V. All rights reserved.