Cannabinoid receptor-interacting protein 1a (CRIP1a) binds to the C-terminal domain of cannabinoid 1 receptor (CB1R) and regulates CB1R activities. In this study, we made Tat-CRIP1a fusion proteins to enhance CRIP1a penetration into neurons and brain and to evaluate the function of CRIP1a in neuroprotection following oxidative stress in HT22 hippocampal cells and transient forebrain ischemia in gerbils. Purified exogenous Tat-CRIP1a was penetrated into HT22 cells in a time and concentration-dependent manner and prevented H₂O₂-induced reactive oxygen species formation, DNA fragmentation, and cell damage. Tat-CRIP1a fusion protein also ameliorated the reduction of 14-3-3η expression by H₂O₂ treatment in HT22 cells. Ischemia–reperfusion damage caused motor hyperactivity in the open field test of gerbils; however, the treatment of Tat-CRIP1a significantly reduced hyperactivity 1 day after ischemia. Four days after ischemia, the administration of Tat-CRIP1a restored the loss of pyramidal neurons and decreased reactive astrocytosis and microgliosis induced by ischemic damage in the hippocampal cornu Ammonis (CA)1 region. Ischemic damage decreased 14-3-3η expression in all hippocampal sub-regions 4 days after ischemia; however, the treatment of Tat-CRIP1 ameliorated the reduction of 14-3-3η expression. These results suggest that Tat-CRIP1a attenuates neuronal damage and hyperactivity induced by ischemic damage, and it restores normal expression levels of 14-3-3η protein in the hippocampus.

中文翻译：

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Tat大麻素受体相互作用蛋白减少缺血诱导的神经元损伤及其与14-3-3η的可能关系。

大麻素受体相互作用蛋白1a（CRIP1a）与大麻素1受体（CB1R）的C末端结构域结合并调节CB1R活性。在这项研究中，我们制作了Tat-CRIP1a融合蛋白来增强CRIP1a渗透到神经元和大脑中，并评估CR221a在HT22海马细胞氧化应激和沙土鼠短暂性前脑缺血后对神经保护的功能。纯化的外源Tat-CRIP1a以时间和浓度依赖性方式渗透到HT22细胞中，并防止H ₂ O ₂诱导的活性氧形成，DNA片段化和细胞损伤。Tat-CRIP1a融合蛋白还改善了H ₂ O ₂对14-3-3η表达的减少HT22细胞中的治疗。在沙鼠的野外试验中，缺血-再灌注损伤导致运动亢进；但是，Tat-CRIP1a的治疗可在缺血1天后显着降低多动症。缺血后四天，Tat-CRIP1a的使用可恢复锥体神经元的丧失，并减少由海马角膜Ammonis（CA）1区缺血性损伤引起的反应性星形细胞增多和小胶质细胞减少。缺血4天后，缺血性损伤使所有海马亚区的14-3-3η表达降低；然而，Tat-CRIP1的治疗改善了14-3-3η表达的减少。这些结果表明，Tat-CRIP1a减轻了由缺血性损伤引起的神经元损伤和过度活跃，并恢复了海马中14-3-3η蛋白的正常表达水平。