β-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E2 synthesis in rat hepatocytes-Kupffer cells
β-oxidation modulates metabolic competition between eicosapentaenoic acid and arachidonic acid regulating prostaglandin E2 synthesis in rat hepatocytes-Kupffer cells
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DOI：
10.1016/j.bbalip.2010.01.002
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发表时间：
2010-04-01
影响因子：
4.8
通讯作者：
Madsen, Lise
中科院分区：
文献类型：
--
作者：
Du, Zhen-Yu;Ma, Tao;Madsen, Lise
N-3PUFA竞争性抑制花生四烯酸(AA)合成膜磷脂和前列腺素E-2(PGE(2))的能力已在单细胞模型中得到很好的证实。在本研究中，我们研究了在大鼠肝细胞-Kupffer细胞(HPC/KC)共培养体系中，当外源L肉碱增强细胞的氧化能力时，AA和EPA对PGE(2)合成的代谢竞争。我们证明，在没有L肉碱的情况下，1)EPA和AA的β-氧化率在HPC和KCs中是相当的2)甘油脂优先结合AA而不是EPA；加入L肉碱可显著增强细胞氧化能力：1)显著增加HPC对AA的氧化作用，但仅略微增加HPC对AA的氧化作用；2)减少酯化作用，但不改变AA优先掺入甘油脂中的情况；3)减轻EPA对AA依赖的PGE(2)合成和COX-2表达的竞争抑制。综上所述，这些结果有力地表明，L肉碱通过促进HPC氧化EPA来影响AA和EPA在肝细胞PG合成中的竞争。这表明n-3PUFA的有益作用，尤其是EPA，受到细胞氧化能力的影响。(C)2010爱思唯尔B.V版权所有
The ability of n-3 PUFA to competitively inhibit the use of arachidonic acid (AA) for membrane phospholipid synthesis and prostaglandin E-2 (PGE(2)) production has been well demonstrated in single cell models In the present study, we investigated the metabolic competition between AA and eicosapentaenoic acid (EPA) for PGE(2) synthesis in a rat hepatocyte-Kupffer cell (HPC/KC) co-culture system when the cellular oxidation capacity was enhanced by exogenous L-carnitine We demonstrate that in the absence of L-carnitine, 1) beta-oxidation rates of EPA and AA were comparable in HPCs and in KCs, 2) AA and not EPA was preferentially incorporated into glycerolipids; and 3) addition of EPA significantly decreased AA-dependent PGE2 synthesis in HPCs and cyclooxygenase-2 (COX-2) expression in co-cultured HPCs/KCs However, enhancing the cellular oxidation capacity by the addition of L-carnitine 1) significantly increased beta-oxidation of EPA in HPCs, but only marginally elevated the oxidation of AA in HPCs and the oxidation of both fatty acids in KCs: 2) decreased the esterification, but did not alter the preferential incorporation of AA into glycerolipids: and 3) alleviated the significant competitive inhibition of AA-dependent PGE(2) synthesis and COX-2 expression by EPA. Taken together, the results strongly suggest that L-carnitine affects competition between AA and EPA in PG synthesis in liver cells by enhancing oxidation of EPA in HPCs This implies that the beneficial effects of n-3 PUFA, especially EPA, are affected by the cellular oxidation capacity. (C) 2010 Elsevier B.V All rights reserved