Obinata Hideru, Hattori Tomoyasu, Nakane Shinji, Tatei Kazuaki, Izumi Takashi
Department of Molecular Biochemistry, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
J Biol Chem. 2005 Dec 9;280(49):40676-83. doi: 10.1074/jbc.M507787200. Epub 2005 Oct 19.
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, [(35)S]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.
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可被多种刺激诱导，导致前B细胞和T细胞在G(2)/M期发生细胞周期停滞。G2A也在动脉粥样硬化病变中的巨噬细胞中表达，提示G2A参与动脉粥样硬化。最近，发现G2A具有质子感应能力。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。在CHO-K1或HEK293细胞中表达的G2A显示出9-HODE诱导的细胞内钙动员、肌醇磷酸积累、cAMP积累抑制、[(35)S]鸟苷5'-3-O-(硫代)三磷酸结合以及MAP激酶激活。此外，G2A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微弱激活。用磷脂酶A(2)水解氧化磷脂酰胆碱（1-棕榈酰-2-亚油酰）也能在表达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及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。
