Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H1/H3 receptors
Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H1/H3 receptors
复制标题
肌肽通过肌肽-组氨酸-组胺途径和 H(1)/H(3) 受体，防止分化的大鼠 PC12 细胞中 NMDA 诱导的神经毒性。
DOI：
10.1016/j.bcp.2006.11.007
复制
发表时间：
2007-03-01
影响因子：
5.8
通讯作者：
Chen, Zhong
中科院分区：
文献类型：
--
作者：
Shen, Yao;Hu, Wei-wei;Chen, Zhong
由于含组氨酸的二肽肌肽（β-丙氨酰-L-组氨酸）被认为在大脑中具有多种生理功能，因此我们在 N-甲基-D-天冬氨酸 (NMDA) 诱导的分化 PC12 细胞神经毒性体外模型中研究了肌肽的神经保护作用及其作用机制。通过 MTT 和 Hoechst 33342 以及碘化丙啶 (PI) 双染色测定，用卡莫辛预处理可增加活力并减少凋亡和坏死细胞的数量。肌肽还可以抑制谷氨酸释放，增加HDC活性以及高效液相色谱（HPLC）检测的细胞内外肌肽、组氨酸和组胺含量。肌肽的保护作用可被α-氟甲基组氨酸逆转，α-氟甲基组氨酸是组氨酸脱羧酶（HDC）的选择性且不可逆的抑制剂。吡拉明和硫过酰胺、选择性中枢组胺 H-1 和 H-3 拮抗剂也显着逆转肌肽的保护作用。此外，肌肽对谷氨酸释放的抑制可被硫过酰胺逆转。因此，肌肽的保护机制可能不仅涉及肌肽-组氨酸-组胺途径，还涉及H-1/H-3受体以及谷氨酸释放的有效抑制。本研究表明肌肽可能是一种内源性保护因子，需要对其作为新的抗兴奋性毒性药物进行进一步研究。 (c) 2006 Elsevier Inc. 保留所有权利。
Since the histidine-containing dipeptide carnosine (beta-alanyl-L-histidine) is believed to have many physiological functions in the brain, we investigated the neuroprotective effects of carnosine and its mechanisms of action in an in vitro model of neurotoxicity induced by N-methyl-D-aspartate (NMDA) in differentiated PC12 cells. Pretreatment with camosine increased the viability and decreased the number of apoptotic and necrotic cells measured by MTT and Hoechst 33342 and propidium iodide (PI) double staining assays. Carnosine also can inhibite the glutamate release and increase HDC activity and the intracellular and extracellular contents of carnosine, histidine and histamine detected by high-performance liquid chromatography (HPLC). The protection by carnosine was reversed by alpha- fluoromethylhistidine, a selective and irreversible inhibitor of histidine decarboxylase (HDC). Pyrilamine and thioperamide, selective central histamine H-1 and H-3 antagonists also significantly reversed the protection of carnosine. Further, the inhibition of glutamate release by carnosine was reversed by thioperamide. Therefore, the protective mechanism of carnosine may not only involve the carnosine-histidine-histamine pathway, but also H-1/H-3 receptors and the effective inhibition of glutamate release. This study indicates that carnosine may be an endogenous protective factor and calls for its further study as a new antiexcitotoxic agent. (c) 2006 Elsevier Inc. All rights reserved.