Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A
Identification of 9-hydroxyoctadecadienoic acid and other oxidized free fatty acids as ligands of the G protein-coupled receptor G2A
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DOI：
10.1074/jbc.m507787200
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发表时间：
2005-12-09
影响因子：
4.8
通讯作者：
Izumi, T
中科院分区：
文献类型：
--
作者：
Obinata, H;Hattori, T;Izumi, T
G2A是一种G蛋白偶联受体，主要在淋巴组织和巨噬细胞中表达。 G2A 可由多种刺激诱导，导致 pro-B 细胞和 T 细胞的细胞周期停滞在 G(2)/M 期。 G2A 也在动脉粥样硬化病变内的巨噬细胞中表达，表明 G2A 参与动脉粥样硬化。最近，G2A被发现具有质子传感能力。在本文中，我们报道了G2A的另一个功能，即作为9-羟基十八碳二烯酸（9-HODE）和其他氧化游离脂肪酸的受体。 G2A 在 CHO-K1 或 HEK293 细胞中表达，表现出 9-HODE 诱导的细胞内钙动员、磷酸肌醇积累、cAMP 积累抑制、[S-35] 鸟苷 5'-3-O-(硫代)三磷酸结合和 MAP 激酶激活。此外，G2A 能被亚油酸和花生四烯酸的各种氧化衍生物激活，但被胆固醇-9-HODE 激活较弱。当用磷脂酶 A(2) 水解时，氧化磷脂酰胆碱（1-棕榈酰-2-亚油酰）也会在表达 G2A 的细胞中引起细胞内钙动员。这些结果表明G2A被磷脂酰胆碱或胆固醇亚油酸酯氧化和随后水解产生的氧化游离脂肪酸激活。因此，G2A 可能在包括动脉粥样硬化在内的多种病理状况中发挥生物学作用。
G2A is a G protein-coupled receptor that is predominantly expressed in lymphoid tissues and macrophages. G2A can be induced by diverse stimuli to cause cell cycle arrest in the G(2)/M phase in pro-B and T cells. G2A is also expressed in macrophages within atherosclerotic lesions, suggesting G2A involvement in atherosclerosis. Recently, G2A was discovered to possess proton-sensing ability. In this paper, we report another function of G2A, that is, as a receptor for 9-hydroxyoctadecadienoic acid (9-HODE) and other oxidized free fatty acids. G2A, expressed in CHO-K1 or HEK293 cells, showed 9-HODE-induced intracellular calcium mobilization, inositol phosphate accumulation, inhibition of cAMP accumulation, [S-35] guanosine 5'-3-O-(thio)triphosphate binding, and MAP kinase activation. Furthermore, G2A was activated by various oxidized derivatives of linoleic and arachidonic acids, but it was weakly activated by cholesteryl-9-HODE. Oxidized phosphatidylcholine (1-palmitoyl-2-linoleoyl) when hydrolyzed with phospholipase A(2) also evoked intracellular calcium mobilization in G2A-expressing cells. These results indicate that G2A is activated by oxidized free fatty acids produced by oxidation and subsequent hydrolysis of phosphatidylcholine or cholesteryl linoleate. Thus, G2A might have a biological role in diverse pathological conditions including atherosclerosis.