Differences between group X and group V secretory phospholipase A 2 in lipolytic modification of lipoproteins

Cellular & Molecular Biology Letters

Shigeki Kamitani²  Kohji Hanasaki¹  Takashi Ono¹  Katsutoshi Yamada¹  Akihiko Saiga¹  Shigenori Yamamoto¹  Yoshikazu Ishimoto¹ 

[1] Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan$$;Department of Molecular Bacteriology, RIMD, Osaka University, Osaka, Japan$$Shionogi Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan$$

关键词: Low-density lipoprotein;    High-density lipoprotein;    Phospholipids;    Calcium ion;   

DOI  :  10.2478/s11658-012-0019-2

学科分类：分子生物学，细胞生物学和基因

来源: Uniwersytet Wroclawski * Wydzial Biotechnologii / University of Wroclaw, Faculty of Biotechnology

【 摘 要 】

Secretory phospholipases A2 (sPLA2s) are a diverse family of low molecular mass enzymes (13–18 kDa) that hydrolyze the sn-2 fatty acid ester bond of glycerophospholipids to produce free fatty acids and lysophospholipids. We have previously shown that group X sPLA2 (sPLA2-X) had a strong hydrolyzing activity toward phosphatidylcholine in low-density lipoprotein (LDL) linked to the formation of lipid droplets in the cytoplasm of macrophages. Here, we show that group V sPLA2 (sPLA2-V) can also cause the lipolysis of LDL, but its action differs remarkably from that of sPLA2-X in several respects. Although sPLA2-V released almost the same amount of fatty acids from LDL, it released more linoleic acid and less arachidonic acid than sPLA2-X. In addition, the requirement of Ca2+ for the lipolysis of LDL was about 10-fold higher for sPLA2-V than sPLA2-X. In fact, the release of fatty acids from human serum was hardly detectable upon incubation with sPLA2-V in the presence of sodium citrate, which contrasted with the potent response to sPLA2-X. Moreover, sPLA2-X, but not sPLA2-V, was found to specifically interact with LDL among the serum proteins, as assessed by gel-filtration chromatography as well as sandwich enzyme-immunosorbent assay using anti-sPLA2-X and anti-apoB antibodies. Surface plasmon resonance studies have revealed that sPLA2-X can bind to LDL with high-affinity (Kd = 3.1 nM) in the presence of Ca2+. Selective interaction of sPLA2-X with LDL might be involved in the efficient hydrolysis of cell surface or intracellular phospholipids during foam cell formation.

【 授权许可】

Unknown