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ATP 结合盒转运蛋白 A7 在胆固醇稳态和宿主防御系统中的作用。

Roles of ATP-binding cassette transporter A7 in cholesterol homeostasis and host defense system.

机构信息

Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

出版信息

J Atheroscler Thromb. 2011;18(4):274-81. doi: 10.5551/jat.6726. Epub 2010 Dec 14.

Abstract

ATP-binding cassette transporter (ABC) A7 is an ABC family protein that is a so-called full-size ABC transporter, highly homologous to ABCA1, which mediates the biogenesis of high-density lipoprotein (HDL) with cellular lipid and helical apolipoproteins. ABCA7 mediates the formation of HDL when exogenously transfected and expressed; however, endogenous ABCA7 was shown to have no significant impact on the generation of HDL and was found to be associated with phagocytosis regulated by sterol regulatory element binding protein 2. Since phagocytosis is one of the fundamental functions of animal cells as an important responsive reaction to infection, injury and apoptosis, ABCA7 seems to be one of the key molecules linking sterol homeostasis and the host defense system. In this context, HDL apolipoproteins were shown to enhance phagocytosis by stabilizing ABCA7 against calpain-mediated degradation and increasing its activity, shedding light on a new aspect of the regulation of the host-defense system.

摘要

三磷酸腺苷结合盒转运蛋白(ABC)A7 是 ABC 家族蛋白,是一种所谓的全尺寸 ABC 转运蛋白,与 ABCA1 高度同源,后者介导细胞脂质和螺旋载脂蛋白的高密度脂蛋白(HDL)的生物发生。当外源性转染和表达时,ABCA7 介导 HDL 的形成;然而,内源性 ABCA7 对 HDL 的产生没有显著影响,并且与固醇调节元件结合蛋白 2 调节的吞噬作用有关。由于吞噬作用是动物细胞的基本功能之一,是对感染、损伤和细胞凋亡的重要反应,因此 ABCA7 似乎是连接胆固醇稳态和宿主防御系统的关键分子之一。在这种情况下,通过稳定 ABCA7 以抵抗钙蛋白酶介导的降解并增加其活性,HDL 载脂蛋白被证明可以增强吞噬作用,这揭示了宿主防御系统调节的一个新方面。

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