TREATMENT OF MACROPHAGES WITH OXIDIZED LOW-DENSITY-LIPOPROTEIN INCREASES THEIR INTRACELLULAR GLUTATHIONE CONTENT
TREATMENT OF MACROPHAGES WITH OXIDIZED LOW-DENSITY-LIPOPROTEIN INCREASES THEIR INTRACELLULAR GLUTATHIONE CONTENT
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DOI：
10.1042/bj2780429
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发表时间：
1991-09-01
影响因子：
4.1
通讯作者：
ROGERS, M
中科院分区：
文献类型：
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作者：
DARLEYUSMAR, VM;SEVERN, A;ROGERS, M
将人单核细胞系THP-1来源的巨噬细胞和C3H/HeJ小鼠腹膜分离的巨噬细胞与氧化型低密度脂蛋白(LDL)共同孵育，测定其总谷胱甘肽含量(氧化+还原)。谷胱甘肽最初的耗尽之后是增加，这样在24小时后谷胱甘肽的含量大约翻了一番。这种反应需要氧化低密度脂蛋白分子的脂相，因为天然低密度脂蛋白和乙酰化低密度脂蛋白对谷胱甘肽水平几乎没有影响。细胞对氧化低密度脂蛋白的反应取决于蛋白质氧化修饰的程度。我们还发现，4-羟基壬烯醛对THP-1细胞也有类似的作用，我们认为氧化低密度脂蛋白中存在的这种或其他醛可以诱导谷胱甘肽的合成，以回应最初的氧化应激和随之而来的谷胱甘肽耗竭。此外，我们发现两种类型的细胞都具有能够解毒醛和过氧化物酶的转移酶和过氧化物酶。然而，氧化型低密度脂蛋白或4-羟基壬烯醛处理细胞24小时，对这些酶的活性没有影响。
Macrophages derived from the human monocyte cell line THP-1 or isolated from the peritoneum of C3H/HEJ mice were incubated with oxidized low-density lipoprotein (LDL) and the total glutathione content (oxidized plus reduced) was measured. An initial depletion of glutathione was followed by an increase, such that after a period of 24 h the glutathione content had approximately doubled. This response required the oxidation of the lipid phase of the LDL molecule, since both native LDL and acetylated LDL had little effect on glutathione levels. The response of the cells to oxidized LDL was dependent on the extent of oxidative modification of the protein. It was also found that 4-hydroxynonenal had a similar effect on THP-1 cells, and we suggest that this or other aldehydes present in oxidized LDL causes the induction of glutathione synthesis in response to an initial oxidative stress and consequent glutathione depletion. In addition, we found that both cell types possess transferases and peroxidases capable of detoxifying aldehydes and peroxides. However, treatment of cells with oxidized LDL or 4-hydroxynonenal for a period of 24 h had no effect on the activities of these enzymes.