Department of Anatomy, Showa University School of Medicine, Shinagawa-ku, Tokyo, Japan.
J Mol Neurosci. 2010 Nov;42(3):397-403. doi: 10.1007/s12031-010-9350-0. Epub 2010 Apr 13.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional peptide that has been shown to be neuroprotective following a diverse range of cell injuries. Although several mechanisms regulating this effect have been reported, no direct evidence has linked PACAP to the regulation of oxidative stress, despite the fact that oxidative stress is a factor in the injury progression that occurs in most models. In the present study, we investigated the plasma oxidative metabolite and anti-oxidation potential levels of PACAP-deficient mice, as well as those of wild-type animals treated with PACAP38. These were assayed by the determination of Reactive Oxidative Metabolites (d-ROMs) and the Biological Anti-oxidant Potential (BAP) using the Free Radical Electron Evaluator system. We also investigated the direct radical scavenging potency of PACAP38 and the functional role of its receptor in the regulation of oxidative stress by PACAP, by using vasoactive intestinal peptide (VIP) and the PACAP receptor antagonist, PACAP6-38. Although younger PACAP null mice displayed no significant effect, greater d-ROMs and lower BAP values were recorded in older animals than in their wild-type littermates. Intravenous injection of PACAP38 in wild-type mice decreased the plasma d-ROMs and BAP values in a dose-dependent manner. These effects were not reproduced using VIP and were abolished by co-treatment with PACAP38 and the PAC1R antagonist PACAP6-38. Taken together, these results suggest that PACAP plays an important role in the physiological regulation of oxidative stress.
垂体腺苷酸环化酶激活肽（PACAP）是一种多功能肽，已被证明在多种细胞损伤后具有神经保护作用。尽管已经报道了几种调节这种作用的机制，但没有直接证据将 PACAP 与氧化应激的调节联系起来，尽管氧化应激是大多数模型中发生的损伤进展的一个因素。在本研究中，我们研究了 PACAP 缺乏型小鼠以及用 PACAP38 处理的野生型动物的血浆氧化代谢物和抗氧化潜力水平。这些通过使用自由基电子评估系统测定反应性氧化代谢物（d-ROMs）和生物抗氧化潜力（BAP）来确定。我们还使用血管活性肠肽（VIP）和 PACAP 受体拮抗剂 PACAP6-38，研究了 PACAP38 的直接清除自由基能力及其受体在 PACAP 调节氧化应激中的功能作用。尽管年轻的 PACAP 缺失型小鼠没有表现出明显的影响，但老年动物的 d-ROMs 和 BAP 值高于其野生型同窝仔。静脉注射 PACAP38 可使野生型小鼠的血浆 d-ROMs 和 BAP 值呈剂量依赖性降低。使用 VIP 无法重现这些作用，并且用 PACAP38 和 PAC1R 拮抗剂 PACAP6-38 共同处理可消除这些作用。综上所述，这些结果表明 PACAP 在氧化应激的生理调节中发挥重要作用。
