Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes.
Oxygen radicals stimulate intracellular proteolysis and lipid peroxidation by independent mechanisms in erythrocytes.
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DOI：
10.1016/s0021-9258(18)47552-7
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发表时间：
1987-06
期刊：
影响因子：
--
通讯作者：
K. Davies;A. Goldberg
中科院分区：
文献类型：
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作者：
K. Davies;A. Goldberg
红细胞暴露于氧自由基可诱导血红蛋白损伤并刺激蛋白质降解、脂质过氧化和溶血。为了确定这些事件是否相关，将兔红细胞与各种氧自由基生成系统和抗氧化剂在37 ℃下孵育。黄嘌呤（X）+黄嘌呤氧化酶（XO）使蛋白质降解（通过游离丙氨酸的产生来测量）增加了11倍以上。当细胞与乙醛加XO、抗坏血酸加铁（Asc + Fe）或单独过氧化氢（H2 O2）孵育时，蛋白水解发生类似的增加。加入XO后，5 min内蛋白水解明显增加，并在5 h内呈线性。与此相反，脂质过氧化，如所示的生产的丙二醛，共轭二烯，或脂质过氧化氢，观察后2小时的孵育与X + XO，乙醛+ XO，或H2 O2。抗坏血酸加Fe 2+诱导蛋白质降解和脂质过氧化;然而，添加各种抗氧化剂（尿酸盐，黄嘌呤，葡萄糖，或丁基羟基甲苯）降低脂质过氧化作用，而不影响蛋白质水解。因此，这些过程似乎通过不同的机制发生。此外，在低浓度的XO，蛋白质降解明显增加，在可检测的脂质过氧化产物的情况下。溶血只发生在少数细胞（9%），并遵循脂质过氧化产物的外观。因此，红细胞对氧自由基的重要反应是受损细胞蛋白的快速降解。增加蛋白水解似乎发生独立的膜损伤，是一个更敏感的指标细胞暴露于氧自由基比脂质过氧化。
Exposure of red blood cells to oxygen radicals can induce hemoglobin damage and stimulate protein degradation, lipid peroxidation, and hemolysis. To determine if these events are linked, rabbit erythrocytes were incubated at 37 degrees C with various oxygen radical-generating systems and antioxidants. Protein degradation, measured by the production of free alanine, increased more than 11-fold in response to xanthine (X) + xanthine oxidase (XO). A similar increase in proteolysis occurred when the cells were incubated with acetaldehyde plus XO, with ascorbic acid plus iron (Asc + Fe), or with hydrogen peroxide (H2O2) alone. Upon addition of XO, increased proteolysis was evident within 5 min and was linear for up to 5 h. In contrast, lipid peroxidation, as shown by the production of malonyldialdehyde, conjugated dienes, or lipid hydroperoxides was observed only after 2 h of incubation with X + XO, acetaldehyde + XO, or H2O2. Ascorbate plus Fe2+ induced both protein degradation and lipid peroxidation; however, the addition of various antioxidants (urate, xanthine, glucose, or butylated hydroxytoluene) decreased lipid peroxidation without affecting proteolysis. Thus, these processes seem to occur by distinct mechanisms. Furthermore, at low concentrations of XO, protein degradation was clearly increased in the absence of detectable lipid peroxidation products. Hemolysis occurred only in a small number of cells (9%) and followed the appearance of lipid peroxidation products. Thus, an important response of red cells to oxygen radicals is rapid degradation of damaged cell proteins. Increased proteolysis seems to occur independently of membrane damage and to be a more sensitive indicator of cell exposure to oxygen radicals than is lipid peroxidation.