High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors.
High affinity binding, endocytosis, and degradation of conformationally modified albumins. Potential role of gp30 and gp18 as novel scavenger receptors.
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DOI：
10.1016/s0021-9258(18)53212-9
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发表时间：
1993-04
期刊：
影响因子：
--
通讯作者：
J. Schnitzer;J. Bravo
中科院分区：
文献类型：
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作者：
J. Schnitzer;J. Bravo
清道夫受体与各种修饰的蛋白质相互作用，介导它们的内吞和降解，并且可能在蛋白质代谢和致病过程如动脉粥样硬化、衰老和糖尿病中起重要作用。许多清道夫受体已被检测到动力学，但很少有这样的结合蛋白已被确定。最近，我们发现，两个膜相关蛋白，gp 30和gp 18，更积极地与白蛋白的构象修改通过化学手段或表面吸附胶体金颗粒比与天然白蛋白。在这项研究中，我们发现，gp 30和gp 18的行为类似于其他已知的清道夫受体。竞争研究表明与其他已知的清道夫受体具有相似的配体结合特征。聚阴离子分子（硫酸葡聚糖、岩藻依聚糖、聚谷氨酸、聚肌苷酸、肝素）和修饰的白蛋白（如经甲酰胺化处理或马来酰化的白蛋白（Mal-牛血清白蛋白））与缀合至胶体金颗粒（A-Au）的白蛋白竞争gp 30和gp 18的印迹。A-Au和Mal-牛血清白蛋白以高亲和力结合培养的内皮细胞。修饰的和天然的白蛋白各自被内化，但只有修饰的白蛋白然后被释放降解。抑制研究表明，只有在阻断gp 30和gp 18的A-Au印迹中有效的相同分子也抑制A-Au降解。添加溶酶体促剂氯喹导致超过70%的降解抑制。观察到培养的平滑肌和内皮细胞沿着与成纤维细胞的A-Au的差异处理的方式与gp 30和gp 18的表达一致。累积起来，这些结果表明，gp 30和gp 18可以介导高亲和力结合，内吞作用，和构象修饰的白蛋白，但不是天然白蛋白的降解。
Scavenger receptors interact with a variety of modified proteins, mediate their endocytosis and degradation, and may play an important role in protein catabolism and pathogenic processes such as atherosclerosis, aging, and diabetes. Many scavenger receptors have been detected kinetically but few such binding proteins have actually been identified. Recently, we found that two membrane-associated proteins, gp30 and gp18, interact more avidly with albumins conformationally modified by chemical means or by surface adsorption to colloidal gold particles than with native albumin. In this study, we show that gp30 and gp18 behave similarly to other known scavenger receptors. Competition studies indicate a similar ligand binding profile to other known scavenger receptors. Polyanionic molecules (dextran sulfate, fucoidan, polyglutamic acid, polyinosinic acid, heparin) and modified albumins such as formaldehyde-treated or maleylated albumin (Mal-bovine serum albumin) competed with albumin conjugated to colloidal gold particles (A-Au) for the blotting of gp30 and gp18. A-Au and Mal-bovine serum albumin bound cultured endothelial cells with high affinity. Modified and native albumins were each internalized, but only modified albumins were then released degraded. Inhibition studies revealed that only the same molecules that were effective in blocking A-Au blotting of gp30 and gp18, also inhibited A-Au degradation. Addition of the lysosomotropic agent chloroquine resulted in more than 70% inhibition of degradation. Differential processing of A-Au by cultured smooth muscle and endothelial cells along with fibroblasts was observed in a manner consistent with gp30 and gp18 expression. Cumulatively, these results suggest that gp30 and gp18 may mediate the high affinity binding, endocytosis, and degradation of conformationally modified albumins but not native albumin.