PACAP protects neuronal PC12 cells from the cytotoxicity of human prion protein fragment 106-126
PACAP protects neuronal PC12 cells from the cytotoxicity of human prion protein fragment 106-126
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DOI：
10.1016/s0014-5793(02)02886-7
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发表时间：
2002-07-03
期刊：
影响因子：
3.5
通讯作者：
Kashimoto, K
中科院分区：
文献类型：
--
作者：
Onoue, S;Ohshima, K;Kashimoto, K
朊病毒蛋白质的错误折叠产生淀粉样蛋白异构体，并且在包括朊病毒疾病在内的神经退行性疾病中显示出加剧神经元损伤。腺苷酸环化酶激活多肽（PACAP）和血管活性肠肽（VIP）在中枢神经系统中有效地刺激轴突发生和神经元细胞的存活。在这里，我们测试了这些神经肽对朊病毒蛋白片段106-126 [PrP（106126）]诱导的PC 12细胞的神经毒性。同时应用神经肽和PrP（106 126）（5 × 10（-5）M）可抑制神经元样PC 12细胞的延迟性死亡。特别地，PACAP 27在低浓度（> 10（-15）M）下抑制PrP（106-126）的神经毒性，其特征在于PrP（106-126）刺激的caspase-3的失活。PACAP 27的神经保护作用被选择性PKA抑制剂H89或MAP激酶抑制剂U 0126拮抗。这些结果表明PACAP 27通过激活PAC 1受体介导的PKA和MAP激酶来减轻PrP（106-126）诱导的PC 12细胞迟发性神经毒性。(C)2002年欧洲生物化学学会联合会。由Elsevier Science B. V.出版，版权所有。
Misfolding of the prion protein Yields amyloidogenic isoforms, and it shows exacerbating neuronal damage in neurodegenerative disorders including prion diseases. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) potently stimulate neuritogenesis and survival of neuronal cells in the central nervous system. Here, we tested these neuropeptides on neurotoxicity in PC12 cells induced by the prion protein fragment 106-126 [PrP (106126)]. Concomitant application of neuropeptide with PrP(106126) (5 X 10(-5) M) inhibited the delayed death of neuron-like PC12 cells. In particular, PACAP27 inhibited the neurotoxicity of PrP(106-126) at low concentrations (> 10(-15) M), characterized by the deactivation of PrP(106-126)-stimulated caspase-3. The neuroprotective effect of PACAP27 was antagonized by the selective PKA inhibitor, H89, or the MAP kinase inhibitor, U0126. These results suggest that PACAP27 attenuates PrP(106-126)-induced delayed neurotoxicity in PC12 cells by activating both PKA and MAP kinases mediated by PAC1 receptor. (C) 2002 Federation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.