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Differences between group X and group V secretory phospholipase A2 in lipolytic modification of lipoproteins

Cellular & Molecular Biology Letters volume 17, pages 459–478 (2012)Cite this article

Abstract

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.

Abbreviations

Ab:

antibody

apoB:

apolipoprotein B

BSA:

bovine serum albumin

COX:

cyclooxygenase

FCS:

fetal calf serum

HDL:

high density lipoprotein

HPLC:

high-performance liquid chromatography

LDL:

low density lipoprotein

lysoPC:

lysophosphatidylcholine

PBS:

phosphate-buffered saline

PC:

phosphatidylcholine

PLA2 :

phospholipase A2

SDS-PAGE:

SDS-polyacrylamide gel electrophoresis

sPLA2 :

secretory PLA2

sPLA2-IB:

group IB sPLA2

sPLA2-IIA:

group IIA sPLA2

sPLA2-V:

group V sPLA2

sPLA2-X:

group X sPLA2

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Authors and Affiliations

  1. Department of Molecular Bacteriology, RIMD, Osaka University, 3-1, Yamada-oka, Suita-shi, Osaka, 565-0871, Japan

    Shigeki Kamitani

  2. Shionogi Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka, Osaka, 561-0825, Japan

    Shigeki Kamitani, Katsutoshi Yamada, Shigenori Yamamoto, Yoshikazu Ishimoto, Takashi Ono, Akihiko Saiga & Kohji Hanasaki

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  1. Shigeki Kamitani
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  2. Katsutoshi Yamada
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Correspondence to Shigeki Kamitani.

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Kamitani, S., Yamada, K., Yamamoto, S. et al. Differences between group X and group V secretory phospholipase A2 in lipolytic modification of lipoproteins. Cell Mol Biol Lett 17, 459–478 (2012). https://doi.org/10.2478/s11658-012-0019-2

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  • DOI: https://doi.org/10.2478/s11658-012-0019-2

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Cellular & Molecular Biology Letters

ISSN: 1689-1392

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