Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase
Oxidative stress increases the expression of the CD36 scavenger receptor and the cellular uptake of oxidized low-density lipoprotein in macrophages from atherosclerotic mice: protective role of antioxidants and of paraoxonase
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DOI：
10.1016/s0021-9150(01)00646-3
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发表时间：
2002-04-01
期刊：
影响因子：
5.3
通讯作者：
Aviram, M
中科院分区：
文献类型：
--
作者：
Fuhrman, B;Volkova, N;Aviram, M
关于氧化应激对巨噬细胞脂质过氧化及其致动脉粥样硬化后果的影响知之甚少。因此，我们质疑细胞过氧化脂质含量和巨噬细胞摄取氧化低密度脂蛋白（Ox-LDL）之间的因果关系。在小鼠衰老过程中，来自E-缺陷（E-0）小鼠的小鼠腹腔巨噬细胞（MPM）中的脂质过氧化物含量逐渐增加至4.6倍，并且伴随着Ox-LDL（90%）细胞摄取和清道夫受体CD 36 mRNA（41%）表达的年龄依赖性增加。通过给予膳食有效的抗氧化剂（维生素E或光甘草定）或通过诱导细胞谷胱甘肽耗竭（通过使用丁硫氨酸亚砜亚胺）分别抑制或刺激细胞氧化应激，分别导致巨噬细胞对Ox-LDL的摄取和细胞CD 36 mRNA表达的显著增加或抑制。将人血清对氧磷酶（PON 1）腹腔注射到E-0小鼠中，导致从2-5月龄E-0小鼠中收获的MPM中脂质过氧化物含量降低40-65%，随后导致. Ox-LDL的摄取和CD 36 mRNA的表达也类似地减少（减少30-40%）。总之，我们的研究结果是第一次证明，巨噬细胞脂质过氧化刺激CD 36 mRNA的表达，并增强细胞摄取的Ox-LDL。(C)2002爱思唯尔科学爱尔兰有限公司保留所有权利。
Little is known about the effects of oxidative stress on macropbage lipid peroxidation and on their atherogenic consequences. Therefore, we questioned the causal relationship between cellular lipid peroxides content and macrophagc uptake of oxidized low-density lipoprotein (Ox-LDL). Lipid peroxide content in mouse peritoneal macrophages (MPMs) from E-deficient (E-0) mice increased progressively by up to 4.6 fold during mice aging, and this was accompanied by an age-dependent increase in the cellular uptake of Ox-LDL (90%), and in the expression of the scavenger receptor CD36 mRNA (41%). Inhibition or stimulation of cellular oxidative stress by administration of dietary potent antioxidants (vitamin E or glabridin) or by inducing cellular glutathione depletion (by using buthionine sulfoximine), respectively, resulted in a significant increment or inhibition of macropbage uptake of Ox-LDL and in cellular CD36) mRNA expression, respectively. Intraperitoneal injection of human serum paraoxonase (PON1) into E-0 mice, resulted in a 40-65% decrement in the lipid peroxide content in MPM harvested from E-0 mice at 2-5 months of age, which subsequently resulted in. a similar reduced uptake of Ox-LDL and expression of CD36 mRNA (by 30-40%). In conclusion, our results are the first to demonstrate that macropliage lipid peroxidation stimulates CD36 mRNA expression and enhances the cellular uptake of Ox-LDL. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.