Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells
Ketosis (acetoacetate) can generate oxygen radicals and cause increased lipid peroxidation and growth inhibition in human endothelial cells
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DOI：
10.1016/s0891-5849(98)00140-3
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发表时间：
1998-12-01
影响因子：
7.4
通讯作者：
Lim, G
中科院分区：
文献类型：
--
作者：
Jain, SK;Kannan, K;Lim, G
细胞脂质过氧化水平升高会增加血管疾病的发生率。酮病导致糖尿病加速细胞损伤和血管疾病的机制尚不清楚；这项研究是为了检验酮体水平升高增加内皮细胞脂质过氧化的假设。人脐静脉内皮细胞(HUVEC)与酮体(乙酰乙酸酯、β-羟基丁酸酯)在37℃培养24 h。乙酰乙酸酯，而不是β-羟基丁酸酯，导致培养的HUVEC脂质过氧化和生长抑制增加。为了确定酮体是否产生氧自由基，使用无细胞缓冲溶液进行了研究。它们表现出显著的超氧化物歧化酶(SOD)抑制乙酰乙酸酯对细胞色素C的还原，但不能被β-羟丁酸还原，这表明乙酰乙酸酯产生了超氧阴离子自由基。更多的研究表明，Fe2+增强了乙酰乙酸酯产生的氧自由基。因此，酮体乙酰乙酸酯水平升高可产生氧自由基，引起内皮细胞脂质过氧化，为糖尿病血管疾病发生率增加提供了可能的机制。(C)1998年爱思唯尔科学公司。
Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular-damage and vascular disease in diabetes is not known; This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes. (C) 1998 Elsevier Science Inc.