Departamento de Biologia Celular e Genética, Centro de Biociências, Universidade Federal do Rio Grande do Norte, UFRN, Campus Universitário, Lagoa Nova, Natal, RN, 59078-900, Brazil.
Instituto Federal de Educação Tecnológica do Rio Grande do Norte, IFRN, Natal, Brazil.
J Neuroinflammation. 2017 Dec 12;14(1):243. doi: 10.1186/s12974-017-1020-5.
The production of reactive oxygen species (ROS) during pneumococcal meningitis (PM) leads to severe DNA damage in the neurons and is the major cause of cell death during infection. Hence, the use of antioxidants as adjuvant therapy has been investigated. Previous studies have demonstrated the possible participation of apurinic/apyrimidinic endonuclease (APE1) during PM. The aims of this study were to investigate the APE1 expression in the cortical and hippocampal tissues of infant Wistar rats infected with Streptococcus pneumoniae and its association with cell death and understand the role of vitamin B6 (vitB6) as a protective factor against cell death.
APE1 expression and oxidative stress markers were analyzed at two-time points, 20 and 24 h post infection (p.i.), in the cortex (CX) and hippocampus (HC) of rats supplemented with vitB6. Statistical analyses were performed by the nonparametric Kruskal-Wallis test using Dunn's post test.
Our results showed high protein levels of APE1 in CX and HC of infected rats. In the CX, at 20 h p.i., vitB6 supplementation led to the reduction of expression of APE1 and apoptosis-inducing factor, while no significant changes in the transcript levels of caspase-3 were observed. Furthermore, levels of carbonyl content and glutamate in the CX were reduced by vitB6 supplementation at the same time point of 20 h p.i.. Since our data showed a significant effect of vitB6 on the CX at 20 h p.i. rather than that at 24 h p.i., we evaluated the effect of administering a second dose of vitB6 at 18 h p.i. and sacrifice at 24 h p.i.. Reduction in the oxidative stress and APE1 levels were observed, although the latter was not significant. Although the levels of APE1 was not significantly changed in the HC with vitB6 adjuvant therapy, vitB6 supplementation prevented the formation of the truncated form of APE1 (34 kDa) that is associated with apoptosis.
Our data suggest that PM affects APE1 expression, which can be modulated by vitB6. Additionally, vitB6 contributes to the reduction of glutamate and ROS levels. Besides the potential to reduce cell death and oxidative stress during neuroinflammation, vitB6 showed enhanced effect on the CX than on the HC during PM.
肺炎球菌性脑膜炎（PM）期间活性氧（ROS）的产生导致神经元中的严重 DNA 损伤，是感染期间细胞死亡的主要原因。因此，已研究使用抗氧化剂作为辅助治疗。先前的研究表明，APURINIC / APYRMIDINIC ENDONUCLEASE（APE1）在 PM 期间可能参与其中。本研究的目的是研究感染肺炎链球菌的 Wistar 幼鼠皮质和海马组织中的 APE1 表达及其与细胞死亡的关系，并了解维生素 B6（vitB6）作为抵抗细胞死亡的保护因子的作用。
在感染后 20 和 24 小时（p.i.），用 vitB6 补充的大鼠皮质（CX）和海马（HC）中分析 APE1 表达和氧化应激标志物。使用非参数 Kruskal-Wallis 检验和 Dunn 事后检验进行统计分析。
我们的结果显示感染大鼠 CX 和 HC 中 APE1 蛋白水平升高。在 CX 中，在 20 h p.i.时，vitB6 补充导致 APE1 和凋亡诱导因子的表达减少，而 caspase-3 的转录水平没有明显变化。此外，在同一 20 h p.i.时，CX 中的羰基含量和谷氨酸水平降低了 vitB6 的补充。由于我们的数据显示 vitB6 在 20 h p.i.对 CX 的影响比 24 h p.i.更为显著，因此我们评估了在 18 h p.i.给予第二剂 vitB6 并在 24 h p.i.进行安乐死的效果。观察到氧化应激和 APE1 水平降低，尽管后者并不显著。尽管 APE1 的水平在 HC 中没有明显变化，但 vitB6 补充可防止与凋亡相关的 APE1（34 kDa）截断形式的形成。
我们的数据表明 PM 会影响 APE1 的表达，而 vitB6 可以调节 APE1 的表达。此外，vitB6 有助于降低谷氨酸和 ROS 水平。除了在神经炎症期间减少细胞死亡和氧化应激的潜力外，vitB6 在 PM 期间对 CX 的作用强于对 HC 的作用。
