Zeya Bushra, Arjuman Albina, Chandra Nimai Chand
Department of Biochemistry, All India Institute of Medical Sciences , Patna 801507, India.
Division of P&I, Indian Council of Medical Research , New Delhi 110 029, India.
Biochemistry. 2016 Aug 16;55(32):4437-44. doi: 10.1021/acs.biochem.6b00469. Epub 2016 Aug 4.
LOX-1, one of the main receptors for oxLDL, is found mainly on the surface of endothelial cells. It is a multifacet 52 kDa type II transmembrane protein that structurally belongs to the C-type lectin family. It exists with short intracellular N-terminal and long extracellular C-terminal hydrophilic domains separated by a hydrophobic domain of 26 amino acids. LOX-1 acts like a bifunctional receptor either showing pro-atherogenicity by activating the NFκB-mediated down signaling cascade for gene activation of pro-inflammatory molecules or playing an atheroprotective agent by receptor-mediated uptake of oxLDL in the presence of an anti-inflammatory molecule like IL-10. Mildly, moderately, and highly oxidized LDL show their characteristic features upon LOX-1 activation and its ligand binding indenture. The polymorphic LOX-1 genes are intensively associated with increased susceptibility to myocardial diseases. The splicing variant LOX IN dimerizes with the native form of LOX-1 and protects cells from damage by oxidized LDL. In the developing field of regenerating medicine, LOX-1 is a potential target for therapeutic intervention.
凝集素样氧化型低密度脂蛋白受体1(LOX-1)是氧化型低密度脂蛋白(oxLDL)的主要受体之一,主要存在于内皮细胞表面。它是一种多面性的52 kDa II型跨膜蛋白,在结构上属于C型凝集素家族。它由短的细胞内N末端和长的细胞外C末端亲水区组成,中间隔着一个26个氨基酸的疏水区。LOX-1起着双功能受体的作用,既可以通过激活NFκB介导的下游信号级联反应来激活促炎分子的基因,从而表现出促动脉粥样硬化性,也可以在存在白细胞介素-10等抗炎分子的情况下,通过受体介导的oxLDL摄取来发挥抗动脉粥样硬化作用。轻度、中度和高度氧化的低密度脂蛋白在LOX-1激活及其配体结合时表现出其特征。LOX-1基因多态性与心肌疾病易感性增加密切相关。剪接变体LOX IN与天然形式的LOX-1二聚化,保护细胞免受氧化型低密度脂蛋白的损伤。在再生医学的发展领域中,LOX-1是治疗干预的潜在靶点。