Galoyan Armen A, Krieglstein Josef, Klumpp Susanne, Danielian Kristina E, Galoian Karine A, Kremers Wolfram, Bezirganyan Kristina B, Davtyan Tigran K
Buniatian Institute of Biochemistry of NAS RA, Yerevan, Republic of Armenia.
Neurochem Res. 2007 Nov;32(11):1898-905. doi: 10.1007/s11064-007-9379-9. Epub 2007 Jun 5.
The AGAPEPAEPAQPGVY proline-rich peptide (PRP-1) was isolated from neurosecretory granules of the bovine neurohypophysis; it is produced by N. supraopticus and N. paraventricularis. It has been shown that PRP-1 has many potentially beneficial biological effects including immunoregulatory, hematopoietic, antimicrobial and anti-neurodegenerative properties. Here we investigated the influence of PRP-1 on staurosporine-induced apoptosis of postnatal hippocampal cells and on doxorubicin-induced bone marrow granulocyte- and monocyte apoptosis. The intention was to further characterize the effect of PRP-1 on the survival rate of neurons and in context with myelopoiesis. We demonstrate that PRP-1 significantly reduced apoptosis of postnatal hippocampal cells induced by staurosporine. The protective effect of PRP-1 against apoptotic cell death was shown to be both time- and dose-dependent. Neuroprotection was more pronounced after prolonged pretreatment of the cells with PRP-1 before the induction of apoptosis with staurosporine. The related peptide [arg(8)]vasopressin did not reveal neuroprotection. PRP-1 also significantly reduced apoptosis of bone marrow monocytes and granulocytes induced by doxorubicin. This protective effect lasted for 2-4 h and was not detectable anymore after 24 h when PRP-1 and doxorubicin were added simultaneously. Previously obtained data and results of the current studies suggested that the hypothalamic PRP-1 possibly represents an endogenous peptide whose primary functions are to regulate myelopoiesis and neuron survival as we provide evidence that PRP can differentially reduce both staurosporine- and doxorubicin-induced hippocampal and bone marrow cell apoptosis.
富含脯氨酸的AGAPEPAEPAQPGVY肽（PRP - 1）是从牛神经垂体的神经分泌颗粒中分离出来的；它由视上核和室旁核产生。已表明PRP - 1具有许多潜在的有益生物学效应，包括免疫调节、造血、抗菌和抗神经退行性特性。在此，我们研究了PRP - 1对星形孢菌素诱导的新生海马细胞凋亡以及阿霉素诱导的骨髓粒细胞和单核细胞凋亡的影响。目的是进一步表征PRP - 1对神经元存活率以及与骨髓生成相关的影响。我们证明PRP - 1显著降低了星形孢菌素诱导的新生海马细胞凋亡。PRP - 1对凋亡细胞死亡的保护作用呈时间和剂量依赖性。在用星形孢菌素诱导凋亡之前，用PRP - 1对细胞进行长时间预处理后，神经保护作用更为明显。相关肽[精氨酸(8)]加压素未显示出神经保护作用。PRP - 1还显著降低了阿霉素诱导的骨髓单核细胞和粒细胞凋亡。这种保护作用持续2 - 4小时，当同时添加PRP - 1和阿霉素时，24小时后不再可检测到。先前获得的数据和当前研究的结果表明，下丘脑PRP - 1可能代表一种内源性肽，其主要功能是调节骨髓生成和神经元存活，因为我们提供了证据表明PRP可以不同程度地减少星形孢菌素和阿霉素诱导的海马和骨髓细胞凋亡。
