Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level

Retinoic acid reduces apoptosis and oxidative stress by preservation of SOD protein level
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DOI:
10.1016/s0891-5849(01)00495-6
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发表时间:
2001-05-15
影响因子:
7.4
通讯作者:
Krieglstein, J
Krieglstein, J
中科院分区:
医学1区
文献类型:
--
作者:
Ahlemeyer, B;Bauerbach, E;Krieglstein, J

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维甲酸(RA)已被证明在多种细胞中发挥抗细胞凋亡和抗氧化活性。在这项研究中,我们确定了RA对铜,锌-超氧化物歧化酶(SOD-1)和锰-超氧化物歧化酶(SOD-2)的mRNA和蛋白水平的影响,在星形孢菌素诱导的细胞凋亡的原代培养物从新生大鼠海马。暴露于staurosporine(300 nM,24 h)的凋亡神经元的百分比增加到62%,而对照组为18%。我们确定的活性氧(ROS)的含量增加,从4至48小时后诱导的损伤。星形孢菌素处理没有显着改变SOD-1和SOD-2的mRNA水平。而SOD-1和SOD-2蛋白水平在加入Staurosporine后24和48 h显著降低。与暴露于星形孢菌素的对照相比。RA(10 nM)处理的培养物显示出在开始暴露于星形孢菌素后24和48 h神经元存活的显著增加、神经元ROS含量的降低以及SOD-1和SOD-2的蛋白水平的增强。结果表明,RA通过阻止SOD-1和SOD-2蛋白水平的下降来减少星形孢菌素诱导的氧化应激和细胞凋亡,从而支持抗氧化防御系统。(C)2001 Elsevier Science Inc.
Retinoic acid (RA) has already been shown to exert antiapoptotic and antioxidative activity in various cells. In this study, we determined the effect of RA on the mRNA and protein levels of the Cu-,Zn-superoxide dismutase (SOD-1) and Mn-superoxide dismutase (SOD-2) during staurosporine-induced apoptosis in primary cultures from neonatal rat hippocampus. Exposure to staurosporine (300 nM, 24 h) increased the percentage of apoptotic neurons to 62% compared with 18% in controls. We determined an increase in the reactive oxygen species (ROS) content from 4 up to 48 h after the induction of the injury. Treatment with staurosporine did not significantly change the mRNA levels of SOD-1 and SOD-2. However, the SOD-1 and SOD-2 protein levels markedly decreased 24 and 48 h after the addition of staurosporine. Compared with staurosporine-exposed controls. RA (10 nM)-treated cultures showed a significant increase in neuronal survival, a reduced neuronal ROS content, and enhanced protein levels of SOD-l and SOD-2 24 and 48 h after the start of the exposure to staurosporine. The results suggest that RA reduced staurosporine-induced oxidative stress and apoptosis by preventing the decrease in the protein levels of SOD-1 and SOD-2, and thus supported the antioxidant defense system. (C) 2001 Elsevier Science Inc.