ApoA-I enhances generation of HDL-like lipoproteins through interaction between ABCA1 and phospholipase C gamma in rat astrocytes

作者：Ito Jin ichi^*; Nagayasu Yuko; Kheirollah Alireza; Abe Dohmae Sumiko; Yokoyama Shinji

来源：Biochimica et Biophysica Acta-Molecular and Cell Biology of Lipids, 2011, 1811(12): 1062-1069.

DOI：10.1016/j.bbalip.2011.08.016

• ApoA-I
• Astrocyte
• ABCA1
• Phospholipase C gamma
• HDL

In the previous paper, we reported that apolipoprotein (apo) A-I enhances generation of HDL-like lipoproteins in rat astrocytes to be accompanied with both increase in tyrosine phosphorylation of phospholipase C gamma (PL-C gamma) and PL-C gamma translocation to cytosolic lipid-protein particles (CLPP) fraction. In this paper, we studied the interaction between apoA-1 and ATP-binding cassette transporter A1 (ABCA1) to relate with PL-C gamma function for generation of HDL-like lipoproteins in the apoA-I-stimulated astrocytes. ABCA1 co-migrated with exogenous apoA-I with apparent molecular weight over 260 kDa on SDS-PAGE when rat astrocytes were treated with apoA-I and then with a cross-linker, BS3. The solubilized ABCA1 of rat astrocytes was associated with the apoA-I-immobilized Affi-Gel 15. An LXR agonist, To901317, increased the cellular level of ABCA1, association of apoA-1 with ABCA1 and apoA-I-mediated lipid release in rat astrocytoma GA-1/Mock cells where ABCA1 expression at baseline is very low. PL-C gamma was co-isolated by apoA-I-immobilized Affi-Gel 15 and co-immunoprecipitated by anti-ABCA1 antibody along with ABCA1 from the solubilized membrane fraction of rat astrocytes. The SiRNA of ABCA1 suppressed not only the PL-C gamma binding to ABCA1 but also the tyrosine phosphorylation of PL-C gamma. A PL-C inhibitor, U73122, prevented generation of apoA-I-mediated HDL-like lipoproteins in rat astrocytes. To901317 increased the association of PL-C gamma with ABCA1 in GA-1/Mock cells dependently on the increase of cellular level of ABCA1 without changing that of PL-C gamma. These findings suggest that the exogenous apoA-1 augments the interaction between PL-C gamma and ABCA1 to stimulate tyrosine phosphorylation and activation of PL-C gamma for generation of HDL-like lipoproteins in astrocytes.

• 出版日期2011-12