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Lysophosphatidylcholine Exhibits Selective Cytotoxicity, Accompanied by ROS Formation, in RAW 264.7 Macrophages

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Lipids

Abstract

Lysophosphatidylcholine (lysoPtdCho) is a component of oxidized low density lipoprotein, and is involved in the pathogenesis of atherosclerosis and inflammation. We studied the effects of lysoPtdCho on cytotoxicity, reactive oxygen species (ROS) production, activation of the extracellular signal-regulated kinase (ERK), mitogen-activated protein kinases and pro-inflammatory gene expression in RAW 264.7 murine macrophage cells. When cells were exposed to lysoPtdCho with various acyl chains in a culture medium containing 10% fetal bovine serum, only 1-linoleoyl (C18:2) lysoPtdCho showed a remarkable cytotoxicity, reaching the highest level at 24 h, and elicited ROS production, suggesting that oxidative stress might be implicated in the cytotoxicity of 1-linoleoyl (C18:2) lysoPtdCho. Presumably in support of this, antioxidants such as magnolol or trolox prevented 1-linoleoyl (C18:2) lysoPtdCho-induced cytotoxicity as well as ROS production, although only partially. Furthermore, the phosphorylation of ERK 1/2 and the expression of pro-inflammatory cytokines such as IL-1β, CCL2 and CCL5 were augmented by 1-linoleoyl (C18:2) lysoPtdCho. Meanwhile, there was no structural importance of the acyl chain for the cytotoxic action of lysoPtdCho during 10 min incubation in serum-free media. Taken together, it is suggested that in a serum-containing medium, 1-linoleoyl (C18:2) lysoPtdCho can cause a significant cytotoxicity through ROS production, probably accompanied by activation of ERK and induction of related inflammatory cytokines, in RAW 264.7 cells.

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Abbreviations

lysoPtdCho:

Lysophosphatidylcholine

ROS:

Reactive oxygen species

FBS:

Fetal bovine serum

MTT:

3-(4,5-Dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide

ERK:

Extracellular signal-regulated kinase

CCL:

Chemotactic cytokines ligand

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Acknowledgment

This work was financially supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) (KRF-2007-531-C00067), Korea.

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Authors and Affiliations

  1. College of Pharmacy, Chungnam National University, Gung-Dong 220, Yuseong-ku, Taejon, 305-764, Republic of Korea

    Cheon Ho Park & Dai-Eun Sok

  2. Department of Food and Nutrition, Chungnam National University, Gung-Dong 220, Yuseong-ku, Taejon, 305-764, Republic of Korea

    Mee Ree Kim

  3. National Research Laboratory of Lipid Metabolism and Atherosclerosis, KRIBB, Taejon, 305-333, Republic of Korea

    Jong-Min Han & Tae-Sook Jeong

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  1. Cheon Ho Park
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Correspondence to Dai-Eun Sok.

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Park, C.H., Kim, M.R., Han, JM. et al. Lysophosphatidylcholine Exhibits Selective Cytotoxicity, Accompanied by ROS Formation, in RAW 264.7 Macrophages. Lipids 44, 425–435 (2009). https://doi.org/10.1007/s11745-009-3286-6

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