High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase: Implications for atherosclerosis
High glucose downregulates the number of caveolae in monocytes through oxidative stress from NADPH oxidase: Implications for atherosclerosis
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DOI：
10.1016/j.bbadis.2006.11.011
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发表时间：
2007-03-01
影响因子：
6.2
通讯作者：
Iguchi, Akihisa
中科院分区：
文献类型：
--
作者：
Hayashi, Toshio;Juliet, Packiasamy A. R.;Iguchi, Akihisa
动脉粥样硬化是一种炎症性疾病，与高血糖密切相关，高血糖是糖尿病的主要症状。小泡是质膜的囊状内陷，介导脂质（如胆固醇）在细胞内的转运。研究了高葡萄糖条件下巨噬细胞小窝蛋白-1的表达与小窝数量的关系。在高葡萄糖浓度的THP-1来源的巨噬细胞中，观察到超氧化物产生增加，诱导型一氧化氮合酶（iNOS）的诱导和小泡蛋白-1的降低呈浓度依赖性。甘露醇作为渗透控制剂，没有效果。此外，通过共聚焦显微镜证实了NADPH氧化酶组分、P47（phox）和caveolin的共定位。原子力显微镜（AFM）研究表明，高葡萄糖浓度减少了小泡的数量和大小。在高血糖培养基中生长的细胞中，DNA片段化的细胞百分比增加。综上所述，高葡萄糖浓度抑制了小窝蛋白-1的表达水平，减少了小窝的数量。这可能是由于超氧化物在巨噬细胞中通过其成分的易位和诱导的iNOS的解偶联来激活NADPH氧化酶。此外，在高葡萄糖浓度下，巨噬细胞可能发生凋亡，导致脂质从巨噬细胞扩散到血管壁的细胞内空间。(c) 2007 Elsevier B.V.版权所有
Atherosclerosis, an inflammatory disease, is closely associated with hyperglycemia, major sign of diabetes mellitus. Caveolae are vesicular invaginations of the plasma membrane that mediate the intracellular transport of lipids such as cholesterol. We evaluated the relationship between the expression of caveolin-1 and the number of caveolae in macrophages under conditions of high glucose concentration. Increased superoxide production, induction of inducible nitric oxide synthase (iNOS), and decreased caveolin-1 were observed in a concentration-dependent manner in THP-1 derived macrophages with high glucose concentrations. Mannitol, used as an osmotic control, showed no effects. Furthermore, colocalization of the NADPH oxidase component, P47(phox), and caveolin was confirmed by confocal microscopy. An atomic force microscopy (AFM) study showed that high glucose concentrations reduced the number and size of the caveolae. The percentage of cells with fragmented DNA was increased in cells grown in hyperglycemic media. Taken together, high glucose concentrations suppress the levels of caveolin-1 expression and reduce the number of caveolae. This might be due to the actions of superoxide via the activation of NADPH oxidase by translocation of its component and uncoupling of induced iNOS in macrophages. Furthermore, the apoptosis of macrophages might occur with high glucose concentrations, leading to the spreading of lipids from macrophages into intracellular spaces in the vessel wall. (c) 2007 Elsevier B.V. All rights reserved.