Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12 cells exposed to ischemia
Neuroprotective effects of carnosine and homocarnosine on pheochromocytoma PC12 cells exposed to ischemia
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DOI：
10.1002/jnr.10228
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发表时间：
2002-05
影响因子：
4.2
通讯作者：
R. Tabakman;P. Lazarovici;R. Kohen
中科院分区：
文献类型：
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作者：
R. Tabakman;P. Lazarovici;R. Kohen
缺乏体外药理模型阻碍了抗缺血性损伤神经保护药物的开发。我们建立了一个缺血模型，将PC12细胞培养暴露于氧气-葡萄糖-剥夺（OGD），然后在常规大气氧气水平下再氧化（18小时）。在该模型中，部分由活性氧（ROS）的产生引起的毒性，通过形态学以及从细胞中释放乳酸脱氢酶（LDH）和前列腺素PGE2来测量。肌肽和同肌肽，组氨酸二肽抗氧化剂，在大脑中发现高浓度，已被认为提供神经保护。使用OGD模型，我们发现5mm肌肽和1mm同肌肽对OGD损伤的神经保护作用最大，约为50%。这种神经保护作用类似于一种已知的抗氧化剂，4 -羟基- 2,2,6,6 -四甲基哌啶- 1 -羟（tempol），并且在PC12细胞的血清剥夺毒性模型中未观察到，这表明肌肽和同型肌肽可能在大脑中作为抗氧化剂-神经保护剂。我们的缺血模型可能为研究组氨酸二肽提供的神经保护机制提供一个有用的工具。©2002 Wiley‐Liss, Inc。
The development of neuroprotective drugs against ischemic insults is hampered by the lack of pharmacological in vitro models. We developed an ischemic model using PC12 cell cultures exposed to oxygen‐glucose‐deprivation (OGD) followed by reoxygenation (18 hr) under regular atmospheric oxygen level. The toxicity induced in this model, that is partially caused by generation of reactive oxygen species (ROS), was measured morphologically as well as by the release of lactate dehydrogenase (LDH) and the prostaglandin PGE2 from the cells. Carnosine and homocarnosine, histidine dipeptides antioxidants, found in high concentration in the brain, have been suggested to provide neuroprotection. Using the OGD model we found that 5 mM carnosine and 1 mM homocarnosine provided maximal neuroprotection of about 50% against OGD insult. This neuroprotective effect was similar to that of a known antioxidant, 4‐hydroxy‐2,2,6,6‐tetramethylpiperidine‐1‐oxyl (tempol), and was not observed in a serum‐deprivation toxicity model of PC12 cells, indicating that carnosine and homocarnosine may act as antioxidant‐neuroprotective agents in the brain. Our ischemic model may provide a useful tool for investigating the mechanisms involved in the neuroprotection afforded by histidine dipeptides. © 2002 Wiley‐Liss, Inc.