3-aminobenzamide prevents restraint-evoked immunocompromise.
3-aminobenzamide prevents restraint-evoked immunocompromise.
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3-氨基苯甲酰胺可预防抑制引起的免疫功能低下。
DOI：
10.1016/j.bbi.2004.11.001
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Nelson,RandyJ
中科院分区：
文献类型：
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作者：
Neigh,GretchenN;Samuelsson,AndrewR;Bowers,StephanieL;Nelson,RandyJ
慢性应激源损害免疫功能，这可能会影响大鼠和小鼠的疾病状态。虽然心理应激源和生理反应之间联系的分子机制仍然难以捉摸，但一种推定的机制是氧化应激。DNA损伤激活聚（ADP-核糖）聚合酶（PARP），这是一种参与DNA修复的核酶;然而，如果DNA损伤是广泛的，那么PARP就具有细胞毒性。由于PARP-1−/−转基因小鼠对慢性应激诱导的免疫功能低下具有抵抗力，因此我们测试了以下假设：束缚前给予3-氨基苯甲酰胺（3-AB）（一种PARP抑制剂）将防止束缚诱发的对新型蛋白质钥孔血蓝蛋白（KLH）的抗体产生抑制。将小鼠每天物理束缚3 h，连续14天，然后用KLH免疫。每日束缚持续另外21天，并评估抗KLH IgG产生。暴露于重复束缚的小鼠降低了抗KLH IgG的浓度，而在每次束缚前用3-AB（0.5、5.0或20.0 mg/kg）处理的小鼠显示出与未受束缚小鼠相似的抗KLH IgG浓度。在束缚范式中给予3-AB（0.5和5.0mg/kg）也促进了皮质酮对束缚的习惯化反应，3-AB（0.5mg/kg）降低了重复束缚对体重的影响。然而，3-AB的免疫保护作用以及内分泌和代谢作用似乎受到明显的调节，因为与内分泌和代谢作用不同，3-AB的免疫保护作用与剂量无关。这些数据表明，PARP抑制剂可能有助于防止免疫功能受损，以应对压力。
Chronic stressors compromise immune function, which may affect disease state in rats and mice. Although the molecular mechanism(s) underlying the link between psychological stressors and physiological responses remain elusive, one putative mechanism is oxidative stress. DNA damage activates poly(ADP-ribose) polymerase (PARP), a nuclear enzyme that participates in DNA repair; if DNA damage is extensive, however, then PARP becomes cytotoxic. Because PARP-1−/−transgenic mice are resistant to chronic stress-induced immunocompromise, we tested the hypothesis that pre-restraint administration of 3-aminobenzamide (3-AB), a PARP inhibitor, would prevent restraint-evoked suppression of antibody production to the novel protein, keyhole limpet hemocyanin (KLH). Mice were physically restrained for 3h daily for 14 consecutive days, then immunized with KLH. Daily restraint continued for an additional 21 days and anti-KLH IgG production was assessed. Mice exposed to repeated restraint reduced concentrations of anti-KLH IgG, whereas, mice treated with 3-AB (0.5, 5.0, or 20.0mg/kg) prior to each bout of restraint displayed anti-KLH IgG concentrations similar to those of unrestrained mice. Treatment with 3-AB (0.5 and 5.0mg/kg) during the restraint paradigm also facilitated habituation of the corticosterone response to restraint, and 3-AB (0.5mg/kg) reduced the effect of repeated restraint on body mass. However, the immunoprotective effects of 3-AB and the endocrine and metabolic effects appear to be distinctly regulated because, unlike the endocrine and metabolic effects, the immunoprotective effects of 3-AB were independent of dose. These data suggest that PARP inhibitors may be useful to prevent compromised immune function in response to stressors.